Journal of
Metabolomics and Systems Biology

  • Abbreviation: J. Metabolomics Syst. Biol.
  • Language: English
  • ISSN: 2805-4210
  • DOI: 10.5897/JMSB
  • Start Year: 2010
  • Published Articles: 9

Review

Taurine is a future biomolecule for potential health benefits: A review

Rajeshwar Nath Srivastava
  • Rajeshwar Nath Srivastava
  • Department of Orthopaedic Surgery, King George’s Medical University, Nabiullah Road, Daliganj, Lucknow, Uttar Pradesh, Pin code-226018 India.
  • Google Scholar
Zeenat Ara
  • Zeenat Ara
  • Department of Orthopaedic Surgery, King George’s Medical University, Nabiullah Road, Daliganj, Lucknow, Uttar Pradesh, Pin code-226018 India.
  • Google Scholar
Shah Waliullah
  • Shah Waliullah
  • Department of Orthopaedic Surgery, King George’s Medical University, Nabiullah Road, Daliganj, Lucknow, Uttar Pradesh, Pin code-226018 India.
  • Google Scholar
Alka Singh
  • Alka Singh
  • Department of Orthopaedic Surgery, King George’s Medical University, Nabiullah Road, Daliganj, Lucknow, Uttar Pradesh, Pin code-226018 India.
  • Google Scholar
Saloni Raj
  • Saloni Raj
  • Department of Orthopaedic Surgery, King George’s Medical University, Nabiullah Road, Daliganj, Lucknow, Uttar Pradesh, Pin code-226018 India.
  • Google Scholar
Abbas Ali Mahdi
  • Abbas Ali Mahdi
  • Department of Biochemistry, King George’s Medical University, Shahmina Road, Chowk, Lucknow, Uttar Pradesh, Pin code-226003, India.
  • Google Scholar
Ravindra Kumar Garg
  • Ravindra Kumar Garg
  • Department of Neurology, King George’s Medical University, Shahmina Road, Chowk, Lucknow, Uttar Pradesh, Pin code-226003, India.
  • Google Scholar
Raja Roy
  • Raja Roy
  • Centre of Biomedical Research, Formerly Centre of Biomedical Magnetic Resonance (CBMR), Sanjay Gandhi Postgraduate Institute of Medical Sciences Campus, Rae Bareli Road, Lucknow, Uttar Pradesh, Pin code-226014, India.
  • Google Scholar


  •  Received: 06 October 2021
  •  Accepted: 09 February 2022
  •  Published: 30 September 2022

 ABSTRACT

Taurine is a sulfur-containing amino acid that is converted to a neutral beta-amino acid, chemically known as (2-Amino-ethane sulfonic acid) having chemical formula C2H7NO3S. It was first isolated from Ox bile, and thus derives its name from the Latin word “Taurus”, meaning 'ox' or 'bull'. This is the only amino acid that is extensively found in animal tissue. The richest source of taurine is meat whereas fish, human tissue, large intestine, and human breast milk are also good/prime sources. It is present in high concentrations in animal tissues, especially the heart, brain, retina, skeletal muscles, large intestines, plasma, blood cells, and leucocytes. Plant protein is devoid of taurine. It involves many functions from prevention to protection, osmoregulation, conjugation of bile, anti-oxidation, membrane stabilization, and modulation of calcium signaling. Hence it is also known as a poly-functional or wonderful molecule. Taurine is significantly involved in functions of the cardiovascular, skeletal muscle, retina, and the central nervous system. It differs from other neuroprotective amino acids due to the presence of sulfonic acid instead of carboxylic acid, and the presence of sulphonate makes it a strong acid. Dietary taurine is beneficial in treating bone-related disorders, neurodegenerative diseases, obesity, and immunological defense against microbes, through enhancing the metabolism/functions of monocytes, macrophages, and other cells of the immune system. The human body contains about 1% body weight as taurine. In this review, we have made attempts to provide synthesis, chemical, biological function of taurine, which may guide and facilitate further research in this area.

Key words: Taurine, spinal cord injury (SCI), taurus, intrauterine growth restriction (IUGR), diabetic peripheral neuropathy (DPN), osmolytes.


 INTRODUCTION

Taurine is the unique non-essential amino acid that has betrayed much attention (Bkaily et al., 2020). It is the first amino acid discovered in 1827 by the  German  Scientists Tiedemann and Gmelin and were the first to extract taurine from the bile of ox (Bas Taurus); from that it derives  its  name,  hence  it  is  accepted as a part of our planet formation. Biologically, it was created some 40 years ago when a good review was published (Jacobsen et al., 1968), which created the curiosity to dig deeper into this wonderful old molecule. It is true to say that taurine is a polyfunctional molecule because it is the only biomolecule involved in so many functions, ranging from defense to prevention (Gupta et al., 2003). Elevation in the level of taurine does not have any side effects, due to the saturable effect of the taurine transporter and the fact that it is usually removed through urine  (Syed et al., 2007).

Taurine is released by the cell when there are some changes in inorganic osmolyte concentrations to make up for any loss of extracellular osmolarity (Pasantes-Morales, 2017). According to Pasantes-Morales (2017), and Schaffer and Kim (2018), it is a neutral zwitter ion. As taurine is a zwitterion, it does not contribute to membrane surface charge. The heart and brain are the only two organs that generate their taurine in a very limited quantity (Schaffer and Kim, 2018). It is found in abundant concentrations in human plasma (near 50-150 mol/L) (Bkaily et al., 2020), as well as in bile, saliva, and heart tissue (6 mol/L). During aging, taurine concentration decrease in the plasma. However, meat, milk, and fish oil are the source of taurine, but the richest source is meat. Daily consumption of meat in human beings provides 400 mg/day of taurine. The daily requirement of taurine in the human body is 3000 mg (Shao and Hathcock, 2008) whereas in published human trials, taurine dosages have ranged from 500 mg to 10 g per day (Shao and Hathcock et al., 2008). In American subjects’, daily intake of taurine has been estimated to be 40-400 mg. Red algae have the highest taurine content whereas green and brown algae have lower taurine content from the Sea of Japan (Adeva-Andany et al., 2018). The human colostrums contain a high concentration of taurine, which is very essential for the development of the retina and brain. Taurine is mostly added in infant formula and parenteral solutions (Park et al., 2014). Taurine concentration in the body varies according to the weight of the subject, hence 70 g taurine is found in a person weighing 70 kg (Huxtable, 1992). Depending on species and cell type, its concentration varies in cells of mammalian and avian ranges from 5 to 60 mM (Wright et al., 1986). Taurine displays minimal  complexities as, it is a naturally occurring amino acid in the body. Studies based on toxicity did not produce genotoxic, carcinogenic, or teratogenic effects (Menzie et al., 2013) whereas in human beings it is sorted  as an essential or functional nutrient (Gaull, 1986, 1989; Bouckenooghe et al., 2006). Taurine is synthesized by a human from methionine  and  obtained  from  dietary sources too (Adeva-Andany et al., 2018). It is also obtained from various types of food, but available in low amounts in milk derived products, such as cow's milk and ice cream, and it is available in high quantity in seafood such as shellfish, particularly mussels, scallops, clams, and in dark meat of chickens and turkeys (Table 1). Interestingly, level of taurine is not affected by cooking (Wojcik et al., 2010).

The European Food Safety Authority (EFSA) recommends that the no observed adverse effect level (NOAEL), of consuming energy drinks is 1000 mg/kg per day  (Menzie et al., 2013). Taurine concentration is roughly four times higher in type I fibres than type II fibres in human skeletal muscles (Page et al., 2019). Taurine is a wonderful molecule as it maintains whole-body homeostasis (Ito et al., 2015)., Some published studies on mouse models have shown effects on skeletal muscles due to disorders of lipid metabolism and glucose dysfunction (Ito et al., 2014), heart (Ito et al., 2008), liver (Warskulat et al., 2006), CNS (Sergeeva et al., 2007), and has been seen in them when a taurine deficiency has been induced in mice by knockout of taurine transporter.

Compared to glutamate, alanine and glycine, taurine is one of the most abundant organic osmolytes (Bkaily et al., 2020). Recently, taurine was proved to be a potent negotiator in the treatment of myotonia, fatigue and alcoholism (Xu et al., 2008). Previously published studies reveal that a high concentration of taurine is found in the epidermis, especially in the epidermal granular layer (Lobo et al., 2001), and with advancing age, concentration of taurine declines as studies reveal that it plays an important role in protecting skin from harmful UV rays and in moisture retention by exerting osmoregulatory and anti-inflammatory effects (Janeke et al., 2003; Anderheggen et al., 2006; Rockel et al., 2007). It is an important component for maintaining normal skin function. A recent study published by Yoshimura et al. (2021) showed that skin samples of hairless mice and Sprague Dawley rats with advanced age content of taurine significantly declines in both the dermis and epidermis, whereas taurine content remains unchanged in the sole.

The immunohistochemical analysis also revealed that reduced taurine content of the skin in older animals were found to be more localised than younger animals, despite no significant variations in localisation between the two age groups. When taurine was added to the drinking water of elderly mice, with 3% (w/v) up to 4 weeks, inclination in taurine level was seen in the epidermis, but not the dermis. Taurine-rich oral ingestion, capsules, and beverages  are   mostly   the  common   mode  of  taurine consumption/supplementation (Ghandforoush-Sattari et al., 2010). Mostly after ingestion, plasma concentration of taurine elevates ~ 10 min and generally peaks (0.03 to 0.06 mmoL) ~ 1 h following ingestion. Adding taurine in sperms preserved at room temperature helps in enhancing the antioxidant ability of sperm, maintains acrosome integrity rate as well as improves the quality of semen preserved at room temperature (Zhang et al., 2021).

As we know, seaweeds of Japan seacoast are rich in taurine especially red algae like mafunori (Gloiopeltis tenax)/fukurofunori (Gloiopeltis furcata), kabanori (Gracilaria textorii), and ogonori (Gracilaria vermiculophylla); hence, these algae may be used to create functional foods which are the richest source of  naturally occurring taurine (Kawasaki et al, 2017). So due to their habit of eating seaweeds, shellfish,  and fishes that are richest source  of  taurine,  Japanese  and  South Koreans have much higher urinary taurine excretion, a marker of the dietary intake of taurine than the subjects of other countries, including Europe and North America as it is proved by  world-wide epidemiological study (Kawasaki et al, 2017).

THE UNIQUE CHEMISTRY OF TAURINE

Taurine is highly acidic, that it almost makes it a zwitterionic. Because of its zwitterionic nature, it is highly water-soluble and lipophilic; hence, due to this character Taurine diffusion via the lipophilic membrane is sluggish. The biological membrane's impermeability to taurine possibly explains the extremely large concentration gradients maintained across the membrane. Due to the zwitterionic characteristic, it has a very strong dipole. Its iso-electric  points  fall  between  carboxylic  amino  acids like; GABA, beta-alanine, and glycine and acidic amino acids like aspartate and glutamate. Because of taurine's particular ionic character, the membrane modulates its action as well as its interaction with Ca2+ and other cations. Taurine is mostly acidic than aspartic acid, glycine, β-alanine and γ-aminobutyric acid (GABA) as its pKa value is 1.5, whereas in comparison to GABA, glycine, and β-alanine, taurine is less basic than these amino acids as pKb value of taurine is 8.82. Due to its cyclic confirmation with an intramolecular hydrogen bond, taurine displays low passive diffusion (Gupta et al., 2005; Chung et al., 2012). Taurine is a monobasic acid shown by X-ray crystallography, and it always exists as a free amino acid as it does not take part in peptide formation. The sulphur in taurine is present in form of sulphonate and may further be oxidized to sulfate. The lowest and highest oxidation state of sulphur is -2 and +6 respectively. There are three conformational forms of taurine according to its conformational analysis in which most stable conformational form is cyclic state.

BIOSYNTHESIS OF TAURINE

Taurine is obtained by the enzymatic reaction of hypotaurine. Based on the nutritional state, protein uptake and amount of cysteine availability in an individual’s body decides the endogeneous synthesis of taurine, thus its synthesis highly varies from individual to individual   (Luca et al., 2015). The availability of cysteine, on the other hand, is determined by the metabolic balance between homocysteine and methionine, folic acid, vitamin B12, and the efficiency of the enzyme methyl-hydro folate reductase.

Compared to rats, taurine synthesis in human through methionine and cysteine is exceedingly lower because of the lower concentration of cysteine sulfinate decarboxylase (a key enzyme in taurine synthesis) in young adult men relative to rats (about three orders of magnitude) (Sturman and Hayes, 1980; Wu, 2020). In comparison to avian and livestock (chickens and ducks, cattle, pigs, and sheep), humans have the lowest capacity to synthesize taurine at any stage of life. A healthy adult's daily taurine production ranges from 50 to 125 mg, depending on his protein intake, nutritional state, and hepatic enzyme activity (Jacobsen and Smith, 1968; Wu, 2020). Due to reduced availability of the amino acid precursors or the suboptimal function of the liver, taurine production in the body is impeded as a result of stress or pathological situations such as heat stress, infection, obesity, diabetes, and cancer. Despite the presence of the maximum amount of precursors of taurine synthesis in infants' and children's diets, they are unable to synthesize enough amount of taurine (Geggel et al., 1985; Wu, 2020). Individuals who only consume plant products are at high risk of taurine deficiency as methionine and cystine (the two precursors of taurine synthesis) are present at very low quantities in most plant-derived proteins (e.g., corn, potato, rice, wheat, and vegetables) (Hou et al., 2019; Wu, 2020).

Algorithm of taurine biosynthesis

Taurine distribution

In the human body, it is the most prevalent intracellular amino acid. . It is not incorporated into proteins and most of it is free due to the absence of carboxyl group and hence not metabolized; besides, it does not participate in gluconeogenesis and therefore does not constitute a direct energy source, whereas in small amounts, it is present as a small peptide in the human brain (Stapleton et al., 1994; Baliou et al., 2021). Its biosynthetic capacity is high in prenatal life, and with aging, continuously starts declining till it reaches its lowest concentration in the elderly stage; further, its concentration also declines during pathological conditions like trauma or sepsis. Because of this reason, taurine biosynthesis does not produce enough amount of taurine required for homeostasis, hence an exogenous dietary supply of taurine becomes necessary (Redmond et al., 1998; Baliou et al., 2021). Taurine content in the body depends on dietary intake of animal/sea origin (Bella et al., 2000). In comparison to individuals on an omnivore diet, taurine content is almost half in vegans (Hansen et al., 2001). Based on taurine uptake, urinary fractional excretion of it ranges between 0.5 to 80.0% (Chesney et al., 1985, 2010; Baliou et al., 2021).

MOLECULAR BASIS OF TAURINE ACTION AGAINST NEUROLOGICAL DISORDERS

Modulation of neuroinflammation

Franscescon et al. (2020), in his study, have shown that taurine is a promising candidate for reducing schizophrenia-like symptoms as it is a neuropsychiatric disorder that affects around 1% of people.

In his study, he demonstrated the neuroprotective effects of taurine against the memory deficiency caused by MK-801 and hyperlocomotion, and underscores the increasing use of zebrafish models in studying the beneficial effects of various compounds against glutamate excitotoxicity. ..Taurine acts in neural stem /progenitor cell proliferation of developing brain (Shivaraj et al., 2012; Hernández-Benítez et al., 2012) where extracellular signal regulated kinase (ERK) 1/2-way may be associated with the development of synapses. Synapsin 1 and postsynaptic density protein which is involved in the development of synapses (Shivaraj et al., 2012) taurine influences the level of these proteins. In cats having deficiency of taurine, kittens have less brain weight and abnormal morphology of cerebellum and visual cortex with delayed migration of neuroblast and glioblast is also observed in the visual cortex. In taurine, deficient kitten pyramidal cell number is decreased and fine branching at the end of neurons (arborization) shows poor development.   Taurine   promotes   cell   proliferation  of human fetal neurons and also involves influencing neurotransmission (Shivaraj et al., 2012). In a recent study, the antidepressant activity of taurine is demonstrated which may be connected to regulating the hypothalamic-pituitary-adrenal axis and promoting the genesis, survival, and increase of neurons inside the hippocampus (Wu et al., 2017; Liu et al., 2011) states that antenatal taurine supplementation can significantly improve the intrauterine growth restriction (IUGR) fetal brain development in the rat model. Antenatal taurine supplementation reduces apoptosis in cerebral cells of fetal rats, promotes cerebral cell regeneration and value-added differentiation, increases cerebral weight and might decrease cerebral injury caused by IUGR. Several studies have described the role of taurine in anti-neuro-inflammatory responses. After induced traumatic brain injury, it has been shown that taurine significantly increases effective recovery as well as reduces glial fibril acidic protein accumulation and water content in the penumbral region. Taurine can protect our brain from traumatic injury which is proved by various studies (Wang et al., 2016), however only very few have suggested that taurine can protect from axonal regeneration after injury. In his study, Niu et al. (2018) showed that in case of traumatic brain injury, taurine exerts protective effect against inflammation, apoptosis, and oxidative stress. He combined astrocytes with neuron cells and treated them with different concentrations of taurine (100, 200, and 300 mg/l) for 72 h, as well as levels of active oxygen, malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, acetylcholinesterase, tumor necrosis factor-α, interleukin-6, caspase-3, p53, B-cell lymphoma 2 and Bcl-2-associated X isolated proteins. These inflammatory, apoptotic, and oxidative markers increase significantly in damaged cells and return to normal levels following the addition of taurine. In his study, Lotocki et al. (2009) showed that in TBI, inflammation is a well-known critical event that occurs due to secretion of cytokines and activation of glial cells. When supplemented through taurine, it exerts its protective and oxidant effect by suppressing inflammatory cytokines such as TNF-α, IL-6, IL-1α, and IL-1β in spinal cord injury and TBI (Sun et al., 2014). In his study, Zhao et al. (2018) states that a high dose of taurine (50 mg/kg) supplementation significantly reduces pathological inflammation and white matter injury following intracerebral hemorrhage, and the mechanism may be related to upregulation of H2S levels and reduced P2X7R expression. In his study, Su et al. (2014) showed the effects of taurine on traumatic brain injury in 72 rats on the functional outcomes of inflammatory cytokines, astrocyte activity, and cerebral edema. Taurine (200 mg/kg) was injected intravenously after injury or daily for 7 days. Taurine improves functional recovery except 1 day and reduced accumulation of glial fibrillary acidic protein  and  water   content  in the penumbral region at 7 days after TBI. Taurine lowers growth-related oncogen (GRO/KC) and interleukin (IL) -1b levels while elevating performance control levels, normal T cells expressed and secreted (RANTES) by 1 day and significantly suppresses 17 cytokines levels: eotaxin, Granulo-cyte colony-stimulating factor (G-CSF), Granulocyte-macrophage colony-stimulating factor (GMCSF), interferon-gamma (IFN-c), IL-1a, IL -1b, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17, leptin, monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-a), vascular endothelial growth factor (VEGF), and only increases MIP-1a levels per week. Heidar et al. (2017) states that during hepatic encephalopathy, brain injury caused by ammonia has been linked to oxidative stress, movement disorders, and cognitive deficits that, if improperly treated, permanent brain injury, coma, and death are all possible outcomes. Taurine supplementation (50, 100, and 200 mg/kg, gavage), reduces oxidative stress biomarkers of brain tissue in cirrhotic animals, and also suppress level of reactive oxygen species, lipid peroxidation, in addition to maintaining the antioxidant capacity of tissues and preventing the depletion of brain glutathione. Animals who were on oral taurine supplementation (200 mg/kg/day) have reported reduced level of ammonia in their plasma and brain. Zhang et al. (2021) in one of his study showed the beneficial effect of taurine against diabetic peripheral neuropathy (DPN). They demonstrated that taurine vitally reduced blood glucose level and extenuate resistant to insulin as well as dysfunction caused by nerve conduction in diabetic rats were also  improved by taurine. Axonal morphology of damaged neurons of the sciatic nerve in diabetic rats is corrected by taurine; also, axonal outgrowth in dorsal root ganglion has been induced by taurine when it is exposed to high glucose. The sciatic nerve of diabetic rats and DRG neurons showed increased phosphorylation levels of PI3K, Akt, and mTOR when exposed to high glucose. As a result of their findings, taurine appears to be a latent candidate for axonopathy and could be a future therapy for DPN protection.

According to the latest investigation by  Chupel et al. (2021), it was demonstrated that for neurodegeneration and cognitive impairments, there is major contribution of immunosenescence; however, these strategies can be attenuated by nonpharmacological strategies, exercises and through amino acid supplementation like taurine. As proven by their study and as we know with aging that taurine content decrease in the body, 48 women were enrolled in the study in 4 categories, that is, exercise training, taurine supplementation, exercise training plus taurine supplementation and control group. After 14 weeks of exercise twice a week and 1.5 g of taurine supplementation, they concluded that exercise combined with taurine supplementation appeared to be a good therapy for improving health-related outcomes in older people. . A published study by Jangra et al.  (2020)  results showed that taurine inhibits RS-induced oxidative stress, neuroinflammation and apoptosis in restraint stress (RS) in rat model. Studies showed the beneficial role of taurine in the case of non-alcoholic fatty liver disease using female Fxr-null mice because their livers exhibit hepatic steatosis and inflammation, a significant decrease in the liver triglycerides, non-esterified fatty acids, and total bile acids were discovered to have high levels of hepatic damage-associated diagnostic indicators, when up to 4 weeks taurine (0.5%) mixed in drinking were given to them. These mice had significantly lower levels of genes related to oxidative stress (Hmox1 and Gsta1), as well as fatty acid synthesis genes (Acc1 and Scd1). The findings imply that consuming taurine reduces hepatic steatosis and dysfunction induced by a deficiency in FXR (Miyata et al., 2020).

Taurine supplementation role

Taurine improves immunocompetence, as well as protects visual function during diabetes (Xu et al., 2008). Taurine is used to inhibit induced cell remodelling by suppressing elevated levels of extracellular inorganic osmolyte as proved by many studies using different types of cell (Bkaily et al., 2020). Taurine acts as an effective osmoregulatory agent as proven by several studies in the literature (Pasantes-Morales, 2017; Schaffer and Kim, 2018). Some studies have shown that when there is an increase in volume, then it induces the release of intracellular taurine (Pasantes-Morales, 2017). Thus, hyposmolarity would induce the extracellular release of taurine, whereas hyperosmolarity would increase intracellular taurine. Ginguay et al. (2016) states that many clinical trials on taurine have promising results which encourage its therapy. Taurine's nutritional value has also been demonstrated in research (McCarty, 2017). Taurine is an essential nutrient in cats and foxes (Ripps and Shen, 2012). Taurine deficiency in these animals shortens their life spans and causes pathological changes (Ito et al., 2014a; Park et al., 2014). In human beings, overt symptoms of taurine deficiency do not easily develop, like in cats and foxes, although parenteral feeding is associated with taurine deficiency (Arrieta et al., 2014). In comparison to cats and fox, tissues of human beings have higher holding capacity of taurine although humans have no capacity to synthesize taurine in large amount. In a study conducted by the World Health Association involving 50 population groups in 25 different countries throughout the world, it was reported that increased consumption of taurine will protect from hypertension and hypercholesterolemia (Sagara et al., 2015). Body mass index is also reduced by taurine supplementation (Yamori et al., 2010); additionally, in case of obese women its supplementation also helps in reducing  elevated  levels  of inflammation markers (Rosa et al., 2014). Predominantly, it is intracellular and moves across the plasma membrane through SLC6A6 (Tau T) and SLC36A1 (PAT1) transporters (Maria et al., 2018). Bhat et al. (2020) states that taurine induces regulation of intrinsically disordered proteins (IDPs) or natively unfolded proteins. Waldron et al. (2018), in their meta-analysis, investigates the effect of oral administration of taurine on resting systolic and diastolic pressure in humans, and their finding reveals that blood pressure can be reduced to a clinically relevant magnitude and without any adverse effect by taurine ingestion at the stated doses and supplementation periods. Zeng et al. (2012) in one of his studies showed the beneficial effect of taurine supplementation on broiler lipid metabolism, they divided 241,1 day old Avian broilers were randomly separated into 5 groups each with three duplicates, for a period of 21-day. The groups were given basal diets containing 0% taurine (control group), 0.05, 0.10, 0.15 and 0.20% taurine, respectively. The results showed that 0.15% dietary taurine increased apparent metabolisable energy and crude fat digestibility (P=0.05), increased the activity of lipase in the pancreas and small intestine (P=0.05), and significantly decreased the content of serum total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), glucose (GLU), and liver TG, FFA (P0.05) compared to the control group. Siefken et al, 2003 demonstrated that taurine transporter TAUT is present in human skin and that’s the reason that epidermal keratinocytes is protected from dehydration because there is accumulation of taurine, In human epidermal region TAUT is expressed as a 69 kDa protein whereas it is absent in the dermis layer of skin. In epidermal itself highest concentration of TAUT is found in the outermost granular keratinocyte layer whereas in the stratum spinosum it is present in lower concentration. When Neonatal normal human epidermal keratinocytes cells were treated (NHEK) with taurine it was seen that it inhibit apoptosis induced either by osmotically or by UV rays. Taurine accumulation is also induced by environmental factors that also effects epidermal barrier function to water loss,taurineloss, taurine helps in preventing surfactant such as SDS induced dry and scaly skin by stimulating epidermal lipid synthesis & modulating the pro-inflammatory response (Waldmann-Laue et al, 2006).

In cardiac mitochondria high concentration of taurine is estimated approximately 70 nmoL/mg,taurine acts as mitochondrial buffer as it has been suggested that elevated level of taurine in heart muscles suppress mitochondrial apoptosis, oxidative and endoplasmic reticu-lum stress,Enzyme acyl-CoA dehydrogenases that controls β-oxidation of fatty acids are shown to have satisfactory activity with mitochondrial taurine serving as a mitochondrial buffering agent,as one of the study on rat model has shown that in taurine deficient heart the rate of β-oxidation of endogenous fatty acids was 31% lower in comparison to control heart (Kurtz  et  al,  2021).  Taurine accumulation is also induced by environmental factors that also effects epidermal barrier function to water loss,taurine helps in preventing surfactant such as SDS induced dry and scaly skin by stimulating epidermal lipid synthesis (Waldmann-Laue et al, 2003).

Tumor necrosis factor-α (TNF-α), one of important proinflammatory cytokine,its production has been found to be downregulated by taurolidine, a derivative of taurine,In human periph-eral blood mononuclear cells from healthy donors which is stimulated by lipopolysaccharide (LPS) 1& INF-γ when treated with Taurolidine it mostly blocked the production of TNF-α by 50-90% ( Wójcik et al, 2010).                                                                                             

Pharmacokinetics of taurine

In humans, one-fourth of bile acids are conjugated with taurine before being absorbed, whereas by the action of tissue enzymes or by bacterial action, taurine is converted to isethionate which is further converted to CO2, water, ammonia, or urea. On an empty stomach, bioavailability of taurine is improved; within 1-2.5 h there is a vast absorption of taurine in the gastrointestinal tract, whereas within 6-8 h after ingestion, taurine has been shown to return to baseline concentrations. The kidney regulates the concentration of taurine via urine excretion; which ranges from 65 to 250 mg daily (Ghandforoush-Sattari et al., 2010). Different muscle types having different concentrations of taurine 1-3 μmol/g taurine has been detected in glycolytic muscle fibres, whereas 15–20 μmol/g taurine has been found in oxidative muscle fibres(Hansen et al., 2010). For taurine import and export, different transporters and channels exist in muscle membrane (Hansen et al., 2010).

Taurine concentration gradually depleted in subjects with chronic kidney disease. Taking dietary L-glutamine supplementation helps in elevating the level of plasma taurine, in contrast to the absence of CKD. One of the previously published studies by Abbasian et al. (2021) showed in an animal model that in the case of CKD, depletion of taurine continuously occurs but it can be rectified by supplementation of L-glutamine.

Other beneficial role of taurine in various diseases

Taurine treatment has shown promising outcomes in the case of osteoarthritis (OA), a disease characterized by deformity in joints, pain stiffness, and swelling affecting a large population, as OA progressed. Collagen II, mRNA and protein levels fell, while ER stress markers (GRP78, GADD153, and Caspase-12) increased. As ER stress markers (GRP78, GADD153, and Caspase-12) increased, chondrocyte viability and Collagen II production were reduced,  and  apoptosis  was promoted. However, in this case, taurine treatment exhibited Anti OA effect by inhibiting these above phenomena. Neutralization of toxic aldehydes and detoxification of xenobiotics is another important function of taurine (Miyazaki et al., 2014). Osteoarthritis is one of the common diseases worldwide. Bian Y et al. (2018) proved in his study on animal model that after surgery, OA induced rat model became relieved from its symptoms after receiving taurine injection in a dose dependent manner. Histopathological analysis revealed that taurine helps in suppressing degeneration of cartilage, loss of matrix and expression of matrix metalloproteinase-3 (MMP-3) and CHOP. According to different studies performed by authors, peculiar features of stroke and neurodegenerative diseases, including Alzheimer’s, Huntington’s and Parkinson’s diseases  are ER stress, mitochondrial dysfunction, and oxidative stress (Prentice et al., 2015). In case of stroke due to release of the immense amount of neurotransmitter, glutamate which overstimulates postsynaptic neurons leading to a neuroexcitotoxic response, characterized by oxidative stress, calcium overload, ER stress, and in some cases cell death (Prentice et al., 2015).

Taurine treatment in the stroke model has been demonstrated to reduce glutamate-mediated toxicity by lowering oxidative stress and [Ca2+] overload, as well as blocking two of the three UPR pathways, while taurine deficiency has been linked to ER stress (Schaffer et al., 2018). However, in chronic situation like Parkinson's, taurine levels decline (Engelborghs et al., 2004). Taurine is available to protect the CNS during the acute phase of the disease, but if BBB taurine transport fails and taurine cannot cross through the BBB itself, there is a lack of adequate concentration for neuroprotection, and the disease progresses to the chronic stage). In another investigation, taurine (200 mg/kg, i.p. for 7 days) was shown to protect against the increased formation of age-related lipid peroxidation products  (Yildirim et al., 2011). By stimulating insulin receptors, taurine helps in enhancing insulin activity and thus played a major role in maintaining euglycemia. In the case of diabetes mellitus (Honsen et al., 2001; Maturo et al., 1988), lower concentration of plasma and platelets’ taurine has been reported; thus, by taurine supplementation, platelets dysfunction and plasma concentration can be restored (Franconi et al., 1995; DeLuca et al., 2001). This is proved by one of the study on diabetic rat model where taurine supplementation improves glucose and fat metabolism as well as help in suppressing insulin resistance (Nakaya et al., 2000). In diabetic subjects, taurine deficiency can be observed by the lower rate of intestinal absorption of taurine and a higher renal excretion rate (Merheb et al., 2007). Decreased taurine concentration has been seen in the liver of diabetic animals (Nandhini et al., 2005). It is therefore confirmed that in diabetes development, taurine deficiency also plays a major role, and  thus  bioavailability  of  taurine  is lower in diabetic subjects; this evidence can be confirmed by two published reports, one of which is Shi et al. (2003) that explains that in case of high glucose condition, activities of taurine transporters are inhibited, and the other by Hansen (2001) which showed that in response to the accumulation of intracellular sorbitol, depletion of intracellular taurine occurs.

After injury, podocyte cells have the very least capacity to regenerate and proliferate as it is a terminally differentiated cell, and reduction in its number leads to diabetic neuropathy as well as precedes the development of renal dysfunction and albuminuria in diabetic patients and animal models of diabetes mellitus, taurine conjugated ursodeoxycholic acid hampers endoplasmic reticulum stress, and apoptosis that induced advanced glycation end products (AGEs) as it also eradicates the AGES induced expression of glucose-regulated protein 78. TUDCA action can be a new interventional treatment that may prove best in suppressing AGEs-induced apoptosis of mouse podocytes in diabetic nephropathy (Chen et al., 2008). Taurine helps in the prevention of mitochondrial dysfunction, as proved by Chen et al. (2008) using rat retinal ganglion cell line by exposing it to hypoxia for 24 h. Rikimaru et al. (2012) in their study used a culture system of the patient suffering from MELAS-derived pathogenic cells and observed that after treating it with a high concentration of taurine (40 mM for 4-day exposure) was unable to reverse the mitochondrial dysfunction. In their study, they showed that high taurine concentration in a dose-dependent manner (0, 20, and 60 mM) increases oxygen consumption rate, reduced oxidative stress, and increases mitochondrial potential. MELAS patients treated with taurine had a reduction in the spread of the ischemic infarct to other brain regions, according to their research. Taurine's protective actions were seen in these patients as an improvement in stroke-like episodes.

By consuming 30 g of beef, a 70 kg healthy male fulfills the daily need of taurine and carnosine (Wu, 2020). Nutritional supplementation of taurine has an immense role in elevating adiponectin levels as well as in decreasing inflammation markers (high-sensitivity C-reactive protein) and lipid peroxidation (TBARS) in obese women within 8 weeks of its supplementation (Rosa et al., 2014). Oral administration of 2 g taurine/day for 4 weeks resulted in clinically significant reductions in the frequency, duration, and intensity of muscle cramps in case of subjects with chronic liver diseases (Vidot et al., 2018), whereas long-term oral administration of taurine (9 or 12 g day-1) for 52 weeks can reduce the genetic disorders caused by a point mutation in mitochondrial DNA as well as reduce the reappearance of stroke-like episodes in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) (Ohsawa et al., 2019).

Taurine    supplementation     helps      in    suppressing complication due to Hypoglycemic effect like diabetic complications such as diabetic nephropathy, retinopathy, and neuropathy (Imae et al, 2014),Taurine exerts protective effect on kidney by attenuating renal damage & suppressing the level of urea nitrogen (BUN) & creatinine  in the blood (Imae et al, 2014).

Administration of taurine helps in the regression of atherogenesis through a different mechanism. Cholesterol level continuously declines due to the administration of taurine in atherogenic animals as demonstrated by many studies (Pettyet al., 1990; Murakami et al., 2010; Murakami et al., 1996). It was observed that in an animal on taurine treated diet, cholesterol level rapidly declines during the regression period of atherogenesis due to taurine’s ability to increase the activity of the enzyme 7-hydroxylase, and to speed up the decomposition of cholesterol (CYP7A1)  (Murakami et al., 2010; Murakami et al., 1996; Yokogoshi et al., 1999; Lam et al., 2006). By decreasing the activity of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA reductase), taurine helps in inhibiting the hepatic biosynthesis of cholesterol esters and triglycerides (Bellentani et al., 1987).

Study by Miyata et al, 2021 demonstrated that in taurine-mediated cholesterol-lowering effect might bile acid/farnesoid X receptor (FXR) signaling is involved,their study showed that by reducing the ileal FXR signaling due to the alteration of ileal bile acid composition taurine partially plays role in cholesterol lowering.

Taurine can be an important preventive factor in case of coronary heart disease which can be emerge as an important molecule for public health. Analysis from the WHO Cardiovascular Diseases and Alimentary Comparison (Yamori Y et al 2010), a multi-center cross-sectional study,observed an inverse corelation between urinary excretion of taurine and Blood pressure (Wójcik et al, 2010).

Ommati et al. (2019) showed the potential effect of taurine on a mouse model of manganism against Mn neurotoxicity, when manganese-exposed mice were treated with different doses of taurine (50, 100, and 500 mg/kg, i.p) alleviated Mn-induced locomotor deficit. According to Yamori et al. (2009), in a genetic rat model of stroke fed with a fish diet rich in taurine, 90% reduction in stroke incidence was observed. No association between serum taurine levels and stroke risk was observed in 14,274 women who were examined in a prospective-case study based on the New York University women’s health study (Wu et al., 2016). Male infertility due to less sperm motility, depression, and cirrhosis may be prevented by taurine (Birdsall et al., 1998; Lourenço et al., 2002), and acute gastric ulcers as well as damaged colon cells are also healed by it (Wingenfeld et al., 2002; Son et al., 1996). Study by Chen et al, 2004 demonstrated in his study the hypocholesterolemic effect of taurine, they observed that formation of cholesterol gallstones increased  by  71%  to 100% due to taurine deficiency whereas there is  0% reduction by taurine supplementation, in addition taurine also helps in reduction of triglycerides (TG) so from their study it is concluded that taurine supplementation does not up-regulate LDL receptor protein level,and reduction in the cholesterol level in circulation is mainly due to its suppressive effect on TG secretion from the liver. 

Role in spinal injury

Almost 90% of all spinal trauma cases in developing countries do not receive any primary medical care or pre-hospital first aid while being transported to a large hospital (Srivastava et al. 2015). In case of the brain, the role of taurine is more or less developed but still, it is a topic of hot debate in case of spinal cord injury and controversies which is a healthy sign for future research. Since many years before a large number of studies demonstrated the action of taurine in the case of the spinal cord that it acts as a neurotransmitter, this interpretation also focuses its possible involvement in the anti-epileptic action on the spinal cord (Kurachi et al., 1985; Kudo et al., 1998). Chen et al., 2020 demonstrated the best therapeutic effect of taurine in combination with ascorbic acid as against SCI-induced rats, combined treatment of both drugs were given to them for 45 consecutive days; it was noticed that there is suppressed level of caspase-3, Bax, pro-NGF, and p53 mRNA expression by more than 30% compared to individual treatments, as well as altered antioxidant markers and induced lipid peroxidant to normal level in SCI-induced rats treated with taurine and ascorbic acid. However, studies are on-going to elucidate the possible role of taurine against SCI as taurine plays a potential role against brain and spinal cord damage caused by trauma. Taurine (2, 5, 15, and 50 mg/kg, IV for 7 days) protected the brain against closed head injury in rats by increasing neurological functioning and decreasing cerebral edoema and BBB permeability. In damaged tissues, taurine treatment boosted SOD activity and glutathione levels while decreasing malondialdehyde and lactic acid levels. Taurine treatment also inhibited cell death in the CA1 and CA3 subfields of the hippocampus (Sun et al., 2015; Dionyssiotis, 2012) where most of the spinal cord injury individuals are malnourished. Daniel et al. (2019) proposed that taurine is one of the most abundant free amino acids in the brain. Through his experiments, he proved that acute taurine treatment promotes axonal regeneration according to SCI in lampreys. This offers a new way to try to promote regeneration of axons after injury to the nervous system in mammalian models. It is still a topic of hot debate whether taurine acts as a neurotransmitter in the case of the spinal cord or not. In general, we can say that to become a neurotransmitter in the case of SCI, taurine should have to be present at  the axon or axon terminal. However, previously recorded data provides evidence of the taurine presence in axons of lamina 1 and 2 and also in the superficial dorsal horn (Lee et al., 1992). However, in the case of SCI as well as in TBI, elevated level of taurine has been seen to indicate its involvement in neuroprotection and regeneration following injury (Magnusson, 1994). Study by Nakajima et al. (2010) showed the beneficial role of taurine treatment at doses of (25, 80, 250, and 800 mg/kg, i.p.) in SCI rat model as changes in motor function disturbances and pathological abnormalities, as well as suppression in the level of IL-6 and myeloperoxidase in a dose-dependent manner, suppression in SCI mediated cyclooxygenase-2 and phosphorylated signal transducer, activation of transcription 3 expression, and reduction in neutrophil accumulation in the sub-arachnoid spaces.

Whereas studies by Chatterji (2017) and Singh et al (2018, 2020) on biofluids serum, urine, and CSF metabolites perturbation through NMR spectroscopy reveals that some metabolites have clear correlation with pattern of recovery in treated ASCI. Through their findings, we can say that may taurine as a metabolite can establish as a potential biomarker of neurological recovery in future.

In one of the recent studies by Vahdat et al. (2021) in the case of 32 TBI subjects who were randomized into two groups, the outcome of their study was that group that received 30 mg/kg/day of taurine, in addition to the Standard Enter a Meal for 14 days have a significant suppressed level of IL-6, one of the important inflammatory markers in TBI subjects as well as enhances the clinical outcome too, in comparison to control group.


 CONCLUSION

In this review, we tried to focus on the taurine origin and its function in different parts of the body and how important this therapeutic molecule is, as it interacts with life processes and evidence for its ability to modify activities in major tissues. Involvement of taurine is due to its unique physiochemical character derived from alpha beta-amino sulphonic acid. In many animals especially in dogs and cats, it is so important that its deficiency causes abnormality. Taurine is considered a therapeutic agent due to exhibiting broad activities, especially for neurological disorders. According to the preceding explanation, its wide inhibitory and regulatory actions demonstrate its therapeutic potential in the treatment of CNS diseases, since from its discovery in 1827 a large number of functions of taurine have been elucidated in experiments focusing on skeletal muscle, cardiovascular system, reproductive and respiratory system. Through multiple processes, including anti-oxidation, energy production, neuromodulation, Ca2+ homeostasis, and osmoregulation,     taurine's         cytoprotective     activity contributes to improvements in human clinical and nutritional health. . Taurine plays a major role against anxiety, depression, neurodegenerative disease like stroke, epilepsy, trauma and chemical-mediated neuronal injuries as well as neurodevelopmental disorders, including Angelman syndrome and Fragile X syndrome. It is worth testing simple, water-soluble, and more lipophilic analogs as a pro-drug of taurine in spinal cord injury (SCI) as they have additional properties than taurine like N-chloro taurine (NCT), an analog of taurine which is more lipophilic than taurine and more effective in scavenging reactive oxygen species (Gupta et al., 2006). We are certain that, with further experimental and clinical trials, these analogues will form a new class of SCI treatments.. A non-randomized controlled trial based on 107 patients with knee OA concluded that in patients with knee OA, vitamin D therapy has a minor but statistically significant therapeutic benefit (Sanghi et al., 2009, 2013), but now many studies are conducted to show taurine effect in case of OA as they get promising result on its supplementation. One of the recent study by Wang et al. (2018) on mouse model has shown that taurine treatment suppressed the OA symptoms and provides protective effect by suppressing MMP-3 and CHOP expression in mouse model, however more human trials on taurine supplementation are still needed in case of OA. One of the cross sectional study by Saraswati et al. (2019) on 56 OA subjects with grade II-IV were recruited in their study in which they demonstrated that taurine supplementation (59.77 mg per day), accelerates SOD dismutase activity. All these findings may open path for future research on taurine in various diseases.


 CONFLICT OF INTERESTS

The authors have not declared any conflict of interests.


 ACKNOWLEDGMENTS

The authors are thankful to The Indian Council of Medical Research (ICMR), New Delhi, (F.N.5/9/1311/2020-Nut) for the financial assistance.



 REFERENCES

Abbasian N, Ghaderi-Najafabadi M, Watson E, Brown J, Bursnall D, Pawluczyk I, Seymour AM, Bevington A (2021). Hepatic cysteine sulphinic acid decarboxylase depletion and defective taurine metabolism in a rat partial nephrectomy model of chronic kidney disease. BMC Nephrology 22(1):1-2.
Crossref

 

Arrieta F, Balsa JA, de la Puerta C, Botella JI, Zamarrón I, Elías E, Del Río JI, Alonso P, Candela Á, Blanco?Colio LM, Egido J(2014). Phase IV prospective clinical study to evaluate the effect of taurine on liver function in postsurgical adult patients requiring parenteral nutrition. Nutrition in Clinical Practice 29(5):672-680.
Crossref

 
 

Baliou S, Adamaki M, Ioannou P, Pappa A, Panayiotidis MI, Spandidos DA, Christodoulou I, Kyriakopoulos AM, Zoumpourlis V (2021). Protective role of taurine against oxidative stress. Molecular Medicine Reports 24(2):1-9.
Crossref

 
 

Bellentani S, Pecorari M, Cordoma P, Marchegiano P, Manenti F, Bosisio E, De Fabiani E, Galli G (1987). Taurine increases bile acid pool size and reduces bile saturation index in the hamster. Journal of Lipid Research 28(9):1021-1027.
Crossref

 
 

Bhat MY, Singh LR, Dar TA (2020). Taurine induces an ordered but functionally inactive conformation in intrinsically Disordered casein proteins. Scientific Reports 10(1):1-1.
Crossref

 
 

Bian Y, Zhang M, Wang K (2018). Taurine protects against knee osteoarthritis development in experimental rat models. The Knee 25(3):374-380.
Crossref

 
 

Birdsall TC (1998). Therapeutic applications of taurine. Alternative medicine review: a journal of clinical therapeutic 3(2):128-136.

 
 

Bkaily G, Jazzar A, Normand A, Simon Y, Al-Khoury J, Jacques D (2020). Taurine and cardiac disease: state of the art and perspectives. Canadian Journal of Physiology and Pharmacology 98(2):67-73.
Crossref

 
 

Bouckenooghe T, Remacle C, Reusens B (2006). Is taurine a functional nutrient? Current Opinion in Clinical Nutrition and Metabolic Care 9(6):728-33.
Crossref

 
 

Chatterji T, Singh S, Sen M, Singh AK, Agarwal GR, Singh DK, Srivastava JK, Singh A, Srivastava RN, Roy R (2017). Proton NMR metabolic profiling of CSF reveals distinct differentiation of meningitis from negative controls. Clinica Chimica Acta 469:42-52.
Crossref

 
 

Chen C, Yang Q, Ma X (2020). Synergistic effect of ascorbic acid and taurine in the treatment of a spinal cord injury-induced model in rats. 3 Biotech 10(2):1-8.
Crossref

 
 

Chen W, Matuda K, Nishimura N, Yokogoshi H (2004). The effect of taurine on cholesterol degradation in mice fed a high-cholesterol diet. Life Sciences 74(15):1889-1898.
Crossref

 
 

Chen Y, Liu CP, Xu KF, Mao XD, Lu YB, Fang L, Yang JW, Liu C (2008). Effect of tau-rine-conjugated ursodeoxycholic acid on endoplasmic reticulum stress and apoptosis induced by advanced glycation end products in cultured mouse podocytes. American Journal of Nephrology 28(6):1014-1022.
Crossref

 
 

Chesney RW, Gusowski N, Dabbagh S (1985). Renal cortex taurine content regulates renal adaptive response to altered dietary intake of sulfur amino acids. The Journal of Clinical Investigation 76(6):2213-2221.
Crossref

 
 

Chesney RW, Han X, Patters AB (2010). Taurine and the renal system. Journal of Biomedical Science 17(1):1-0.
Crossref

 
 

Chung MC, Malatesta P, Bosquesi PL, Yamasaki PR, Santos JL, Vizioli EO (2012). Advances in drug design based on the amino acid approach: Taurine analogues for the treatment of CNS diseases. Pharmaceuticals 5(10):1128-1146.
Crossref

 
 

Chupel MU, Minuzzi LG, Furtado GE, Santos ML, Ferreira JP, Filaire E, Teixeira AM (2021). Taurine supplementation reduces myeloperoxidase and matrix-metalloproteinase-9 levels and improves the effects of exercise in cognition and physical fitness in older women. Amino Acids 53(3):333-345.
Crossref

 
 

De Luca A, Pierno S, Camerino DC (2015). Taurine: the appeal of a safe amino acid for skeletal muscle disorders. Journal of translational medicine 13(1):1-8.
Crossref

 
 

De Luca G, Calpona PR, Caponetti A, Romano G, Di Benedetto A, Cucinotta D, Di Giorgio RM (2001). Taurine and osmoregulation: platelet taurine content, uptake, and release in type 2 diabetic patients. Metabolism-Clinical and Experimental 50(1):60-64.
Crossref

 
 

Engelborghs, S., Marescau, B., and De Deyn, P. P. (2003). Amino acids and biogenic amines in cerebrospinal fluid of patients with Parkinson's disease. Neurochemical Research. 28(8):1145-1150. 
Crossref

 
 

Franconi F, Bennardini F, Mattana A, Miceli M, Ciuti M, Mian M, Gironi A, Anichini R, Seghieri G (1995). Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation. The American Journal of Clinical Nutrition 61(5):1115-1119.
Crossref

 
 

Franscescon F, Müller TE, Bertoncello KT, Rosemberg DB (2020). Neuroprotective role of taurine on MK-801-induced memory impairment and hyperlocomotion in zebrafish. Neurochemistry international 135:104710.
Crossref

 
 

Gaull GE (1986). Taurine as a conditionally essential nutrient in man. Journal of the American College of Nutrition 5(2):121-125.
Crossref

 
 

Gaull GE (1989). Taurine in pediatric nutrition: review and update. Pediatrics 83(3):433-442.
Crossref

 
 

Geggel HS, Ament ME, Heckenlively JR, Martin DA, Kopple JD (1985). Nutritional requirement for taurine in patients receiving long-term parenteral nutrition. New England Journal of Medicine 312(3):142-146.
Crossref

 
 

Ghandforoush-Sattari M, Mashayekhi S, Krishna CV, Thompson JP, Routledge PA (2010). Pharmacokinetics of oral taurine in healthy volunteers. Journal of Amino Acids 2010.
Crossref

 
 

Ginguay A, De Bandt JP, Cynober L (2016). Indications and contraindications for infusing specific amino acids (leucine, glutamine, arginine, citrulline, and taurine) in critical illness. Current Opinion in Clinical Nutrition and Metabolic Care 19(2):161-169.
Crossref

 
 

Gupta RC, Seki Y, Yosida J (2006). Role of taurine in spinal cord injury. Current neurovascular research 3(3):225-235.
Crossref

 
 

Gupta, RC, Kim SJ (2003). Role of taurine in organ's dysfunction and in their alleviation. Critical Care and Shock 6:191-197.

 
 

Gupta, RC, Win, T, Bittner S (2005). Taurine analogs a new class of therapeutic Ret-rospect and prospect. Current medicinal chemistry 12(17):2021-2039.
Crossref

 
 

Hansen SH (2001). The role of taurine in diabetes and the development of diabetic complications. Diabetes/Metabolism Research and Reviews 17(5):330-346.
Crossref

 
 

Hernández-Benítez R, Ramos-Mandujano G, Pasantes-Morales H (2012). Taurine stimulates proliferation and promotes neurogenesis of mouse adult cultured neural stem/progenitor cells. Stem Cell Research 9(1):24-34.
Crossref

 
 

Hou X, Wang Z, Ding F, He Y, Wang P, Liu X, Xu F, Wang J, Yang Y (2019). Taurine transporter regulates adipogenic differentiation of human adipose-derived stem cells through affecting Wnt/β-catenin signaling pathway. International Journal of Biological Sciences 15(5):1104.
Crossref

 
 

Huxtable RJ (1992). Physiological actions of taurine. Physiological reviews 72(1):101-163.
Crossref

 
 

Imae M, Asano T, Murakami S (2014). Potential role of taurine in the prevention of diabetes and metabolic syndrome. Amino Acids 46(1):81-88.
Crossref

 
 

Ito T, Kimura Y, Uozumi Y, Takai M, Muraoka S, Matsuda T, Ueki K, Yoshiyama M, Ikawa M, Okabe M, Schaffer SW (2008). Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy. Journal of Molecular and Cellular Cardiology 44(5):927-937.
Crossref

 
 

Ito T, Yoshikawa N, Inui T, Miyazaki N, Schaffer SW, Azuma J (2014). Tissue depletion of taurine accelerates skeletal muscle senescence and leads to early death in mice. PloS One 9(9):e107409.
Crossref

 
 

Ito T, Yoshikawa N, Ito H, Schaffer SW (2015). Impact of taurine depletion on glucose control and insulin secretion in mice. Journal of Pharmacological Sciences 129(1):59-64.
Crossref

 
 

Jacobsen JG, Smith LH (1968). Biochemistry and physiology of taurine and taurine derivatives. Physiological Reviews 48(2):424-511.
Crossref

 
 

Jangra A, Rajput P, Dwivedi DK, Lahkar M (2020). Amelioration of repeated restraint stress-induced behavioral deficits and hippocampal anomalies with taurine treatment in mice. Neurochemical Research 45(4):731-740.
Crossref

 
 

Kawasaki A, Ono A, Mizuta S, Kamiya M, Takenaga T, Murakami S (2017). The taurine content of Japanese seaweed. In Taurine 10 (pp. 1105-1112). Springer, Dordrecht.
Crossref

 
 

Kurtz JA, VanDusseldorp TA, Doyle JA, Otis JS (2021). Taurine in sports and exercise. Journal of the International Society of Sports Nutrition 18(1):1-20.
Crossref

 
 

La Bella V, Piccoli F (2000). Differential effect of β-N-oxalylamino-l-alanine, the Lathyrus sativus neurotoxin, and (±)-α-amino-3-hydroxy-5-methylisoxazole-4-propionate on the excitatory amino acid and taurine levels in the brain of freely moving rats. Neurochemistry international 36(6):523-530.
Crossref

 
 

Lam NV, Chen W, Suruga K, Nishimura N, Goda T, Yokogoshi H (2006). Enhancing effect of taurine on CYP7A1 mRNA expression in Hep G2 cells. Amino Acids 30(1):43-48.
Crossref

 
 

Liu J, Liu L, Chen H (2011). Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction. Neuroscience 181:265-270.
Crossref

 
 

Lobo MV, Alonso FJ, Latorre A, del Río RM (2001). Taurine levels and localisation in the stratified squamous epithelia. Histochemistry and Cell Biology 115(4):341-347.
Crossref

 
 

Maturo J, Kulakowski EC (1988). Taurine binding to the purified insulin receptor. Biochemical Pharmacology 37(19):3755-3760.
Crossref

 
 

McCarty MF (2017). Supplementation with phycocyanobilin, citrulline, taurine, and Supranutritional doses of folic acid and Biotin-Potential for preventing or slowing the progression of diabetic complications. InHealthcare 5(1):15. Multidisciplinary Digital Publishing Institute.
Crossref

 
 

Menzie J, Prentice H, Wu JY (2013). Neuroprotective mechanisms of taurine against ischemic stroke. Brain Sciences 3(2):877-907.
Crossref

 
 

Merheb M, Daher RT, Nasrallah M, Sabra R, Ziyadeh FN, Barada K (2007). Taurine intestinal absorption and renal excretion test in diabetic patients: a pilot study. Diabetes Care 30(10):2652-2654.
Crossref

 
 

Miyata M, Matsushita K, Shindo R, Shimokawa Y, Sugiura Y, Yamashita M (2020). Selenoneine ameliorates hepatocellular injury and hepatic steatosis in a mouse model of NAFLD. Nutrients 12(6):1898.
Crossref

 
 

Miyata M, Tanaka T, Takahashi K, Funaki A, Sugiura Y (2021). Cholesterol-lowering effects of taurine through the reduction of ileal FXR signaling due to the alteration of ileal bile acid composition. Amino Acids 53(10):1523-1532.
Crossref

 
 

Murakami S, Sakurai T, Tomoike H, Sakono M, Nasu T, Fukuda N (2010). Prevention of hypercholesterolemia and atherosclerosis in the hyperlipidemia-and atherosclerosis-prone Japanese (LAP) quail by taurine supplementation. Amino Acids 38(1):271-278.
Crossref

 
 

Murakami S, Yamagishi I, Asami Y, Ohta Y, Toda Y, Nara Y, Yamori Y (1996). Hypolipidemic effect of taurine in stroke-prone spontaneously hypertensive rats. Pharmacology 52(5):303-313.
Crossref

 
 

Miyazaki T, Matsuzaki Y (2014). Taurine and liver diseases: a focus on the heterogeneous protective properties of taurine. Amino acids 46(1):101-110.
Crossref

 
 

Nakajima Y, Osuka K, Seki Y, Gupta RC, Hara M, Takayasu M, Wakabayashi T (2010). Taurine reduces inflammatory responses after spinal cord injury. Journal of neurotrauma 27(2):403-410.
Crossref

 
 

Niu X, Zheng S, Liu H, Li S (2018). Protective effects of taurine against inflammation, apoptosis, and oxidative stress in brain injury. Molecular Medicine Reports 18(5):4516-4522.
Crossref

 
 

Ohsawa Y, Hagiwara H, Nishimatsu SI, Hirakawa A, Kamimura N, Ohtsubo H, Fukai Y, Murakami T, Koga Y, Goto YI, Ohta S (2019). Taurine supplementation for prevention of stroke-like episodes in MELAS: a multicentre, open-label, 52-week phase III trial. Journal of Neurology, Neurosurgery and Psychiatry 90(5):529-536.
Crossref

 
 

Ommati MM, Heidari R, Ghanbarinejad V, Abdoli N, Niknahad H (2019). Taurine treatment provides neuroprotection in a mouse model of manganism. Biological trace element research 190(2):384-395.
Crossref

 
 

Page LK, Jeffries O, Waldron M (2019). Acute taurine supplementation enhances thermoregulation and endurance cycling performance in the heat. European Journal of Sport Science 19(8):1101-1109.
Crossref

 
 

Park E, Park SY, Dobkin C, Schuller-Levis G (2014). Development of a novel cysteine sulfinic acid decarboxylase knockout mouse: dietary taurine reduces neonatal mortality. Journal of Amino Acids 12 p.
Crossref

 
 

Pasantes-Morales H (2017). Taurine homeostasis and volume control. Glial Amino Acid Transporters pp. 33-53.
Crossref

 
 

Petty MA, Kintz J, DiFrancesco GF (1990). The effects of taurine on atherosclerosis development in cholesterol-fed rabbits. European Journal of Pharmacology 180(1):119-127.
Crossref

 
 

Prentice H, Modi JP, Wu JY (2015). Mechanisms of neuronal protection against excitotoxicity, endoplasmic reticulum stress, and mitochondrial dysfunction in stroke and neurodegenerative diseases. Oxidative Medicine and Cellular Longevity.
Crossref

 
 

Redmond HP, Stapleton PP, Neary P, Bouchier-Hayes D (1998). Immunonutrition: the role of taurine. Nutrition 14(7-8):599-604.
Crossref

 
 

Rikimaru M, Ohsawa Y, Wolf AM, Nishimaki K, Ichimiya H, Kamimura N, Nishi-matsu SI, Ohta S, Sunada Y (2012). Taurine ameliorates impaired the mitochondrial function and prevents stroke-like episodes in patients with MELAS. Internal Medicine 51(24):3351-3367.
Crossref

 
 

Ripps H, Shen W (2012). taurine: a "very essential" amino acid. Molecular Vision 18:2673.

 
 

Rockel N, Esser C, Grether-Beck S, Warskulat U, Flögel U, Schwarz A, Schwarz T, Yarosh D, Häussinger D, Krutmann J (2007). The osmolyte taurine protects against ultraviolet B radiation-induced immunosuppression. The Journal of Immunology 179(6):3604-3612.
Crossref

 
 

Rosa FT, Freitas EC, Deminice R, Jordao AA, Marchini JS (2014). Oxidative stress and inflammation in obesity after taurine supplementation: a double-blind, placebo-controlled study. European Journal of Nutrition 53(3):823-830.
Crossref

 
 

Sagara M, Murakami S, Mizushima S, Liu L, Mori M, Ikeda K, Nara Y, Yamori Y (2015). Taurine in 24-h urine samples is inversely related to cardiovascular risks of middle aged subjects in 50 populations of the world. In Taurine 9: 623-636. Springer, Cham.
Crossref

 
 

Sanghi D, Avasthi S, Srivastava RN, Singh A (2009). "Nutritional Factors and Osteoarthritis- A Review Article". Internet Journal of Medical Update 4(1).
Crossref

 
 

Sanghi D, Mishra A, Sharma AC, Singh A, Natu SM, Agarwal S, Srivastava RN (2013). Does vitamin D improve osteoarthritis of the knee: a randomized controlled pilot trial. Clinical Orthopaedics and Related Research® 471(11):3556-62.
Crossref

 
 

Schaffer S, Kim HW (2018). Effects and mechanisms of taurine as a therapeutic agent. Biomolecules and Therapeutics 26(3):225.
Crossref

 
 

Sergeeva OA, Fleischer W, Chepkova AN, Warskulat U, Häussinger D, Siebler M, Haas HL (2007). GABAA?receptor modification in taurine transporter knockout mice causes striatal disinhibition. The Journal of Physiology 585(2):539-48.
Crossref

 
 

Shao A, Hathcock JN (2008). Risk assessment for the amino acids taurine, L-glutamine and L-arginine. Regulatory Toxicology and Pharmacology 50(3):376-99.
Crossref

 
 

Shivaraj MC, Marcy G, Low G, Ryu JR, Zhao X, Rosales FJ, Goh EL (2012). Taurine induces proliferation of neural stem cells and synapse development in the developing mouse brain.
Crossref

 
 

Siefken W, Carstensen S, Springmann G, Wittern KP, Wenck H, Stäb F, Sauermann G, Schreiner V, Doering T, Janeke G, Bleck O (2003). Role of taurine accumulation in keratinocyte hydration. Journal of investigative dermatology 121(2):354-361.
Crossref

 
 

Singh A, Srivastava RN, Agrahari A, Singh S, Raj S, Chatterji T, Mahdi AA, Garg RK, Roy R (2018). Proton NMR based serum metabolic profile correlates with the neurological recovery in treated acute spinal cord injury (ASCI) subjects: A pilot study. Clinica Chimica Acta 480:150-160.
Crossref

 
 

Singh A, Srivastava RN, Chatterji T, Singh S, Raj L, Mahdi AA, Garg RK, Roy R (2020). 1H NMR urine metabolomics is an effective prognostic indicator in acute spinal cord injury (ASCI): A prospective case-control study. Journal of Metabolomics and Systems Biology 4(1):1-21.

 
 

Sobrido-Cameán D, Fernández-López B, Pereiro N, Lafuente A, Rodicio MC, Barreiro-Iglesias A (2020). Taurine promotes axonal regeneration after a complete spinal cord injury in lampreys. Journal of neurotrauma 37(6):899-903.
Crossref

 
 

Son M, Kim HK, Kim WB, Yang J, Kim BK (1996). Protective effect of taurine on indomethacin-induced gastric mucosal injury. Advances in Experimental Medicine and Biology 403:147-155.
Crossref

 
 

Son M, Kim HK, Kim WB, Yang J, Kim BK (1996). Protective effect of taurine on indomethacin-induced gastric mucosal injury. Archives of Pharmacal Research 19(2):85-90.
Crossref

 
 

Srivastava RN, Singh A, Garg RK, Agarwal A, Raj S (2015). Epidemiology of traumatic spinal cord injury: A SAARC perspective. International Journal of Biochemistry and Molecular Biology 3:9-22.

 
 

Stapleton PP, Mahon TM, Nowlan P, Bloomfield FJ (1994). Effects of in-vivo administration of taurine and HEPES on the inflammatory response in rats. Journal of pharmacy and pharmacology 46(9):745-50.
Crossref

 
 

Sturman JA, Hayes KC (1980). The biology of taurine in nutrition and development. InAdvances in nutritional research (pp. 231-299). Springer, Boston, MA.
Crossref

 
 

Su Y, Fan W, Ma Z, Wen X, Wang W, Wu Q, Huang H (2014). Taurine improves functional and histological outcomes and reduces inflammation in traumatic brain injury. Neuroscience 266:56-65.
Crossref

 
 

Sun Q, Hu H, Wang W, Jin H, Feng G, Jia N (2014). Taurine attenuates amyloid β 1-42-induced mitochondrial dysfunction by activating of SIRT1 in SK-N-SH cells. Biochemical and Biophysical Research Communications 447(3):485-9.
Crossref

 
 

Sun M, Zhao Y, Gu Y, Zhang Y (2015). Protective effects of taurine against closed head in-jury in rats. Journal of Neurotrauma. 32(1):66-74.
Crossref

 
 

Vahdat M, Hosseini SA, Soltani F, Cheraghian B, Namjoonia M (2021). The effects of Taurine supplementation on inflammatory markers and clinical outcomes in patients with traumatic brain injury: a double-blind randomized controlled trial. Nutrition Journal 20(1):1-9.
Crossref

 
 

Vidot H, Cvejic E, Carey S, Strasser SI, McCaughan GW, Allman?Farinelli M, Shackel NA (2018). Randomised clinical trial: oral taurine supplementation versus placebo reduces muscle cramps in patients with chronic liver disease. Alimentary pharmacology & therapeutics 48(7):704-12.
Crossref

 
 

Waldmann-Laue MA, Forster TH (2006). Taurine improves epidermal barrier properties stressed by surfactantsA role for osmolytes in barrier homeostasis. Journal of Cosmetic Science 57:1-0.

 
 

Waldron M, Patterson SD, Tallent J, Jeffries O (2018). The effects of oral taurine on resting blood pressure in humans: a meta-analysis. Current Hypertension Reports 20(9):1-8.
Crossref

 
 

Wang Q, Fan W, Cai Y, Wu Q, Mo L, Huang Z, Huang H (2016). Protective effects of taurine in traumatic brain injury via mitochondria and cerebral blood flow. Amino Acids 48(9):2169-2177.
Crossref

 
 

Warskulat U, Borsch E, Reinehr R, Heller?Stilb B, Mönnighoff I, Buchczyk D, Donner M, Flögel U, Kappert G, Soboll S, Beer S (2006). Chronic liver disease is triggered by taurine transporter knockout in the mouse. The FASEB Journal 20(3):574-576.
Crossref

 
 

Lotocki G, de Rivero Vaccari JP, Perez ER, Sanchez-Molano J, Furones-Alonso O, Bramlett HM, Dietrich WD (2009). Alterations in blood-brain barrier permeability to large and small molecules and leukocyte accumulation after traumatic brain injury: effects of post-traumatic hypothermia. Journal of Neurotrauma 26(7):1123-1134.
Crossref

 
 

Wójcik OP, Koenig KL, Zeleniuch-Jacquotte A, Costa M, Chen Y (2010). The potential protective effects of taurine on coronary heart disease. Atherosclerosis 208(1):19-25.
Crossref

 
 

Wright CE, Tallan HH, Lin YY, Gaull GE (1986). Taurine: biological update. Annual Review of Biochemistry 55(1):427-453.
Crossref

 
 

Wu G (2020). Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health. Amino Acids 52(3):329-60.
Crossref

 
 

Wu GF, Ren S, Tang RY, Xu C, Zhou JQ, Lin SM, Feng Y, Yang QH, Hu JM, Yang JC (2017). Antidepressant effect of taurine in chronic unpredictable mild stress-induced de-pressive rats. Scientific reports 7(1):1-4.
Crossref

 
 

Xu YJ, Arneja AS, Tappia PS, Dhalla NS (2008). The potential health benefits of taurine in cardiovascular disease. Experimental and Clinical Cardiology 13(2):57.

 
 

Yamori Y, Taguchi T, Mori H, Mori M (2010). Low cardiovascular risks in the middle aged males and females excreting greater 24-hour urinary taurine and magnesium in 41 WHO-CARDIAC study populations in the world. Journal of Biomedical Science 17(1):1-5.
Crossref

 
 

Yokogoshi H, Mochizuki H, Nanami K, Hida Y, Miyachi F, Oda H (1999). Dietary taurine enhances cholesterol degradation and reduces serum and liver cholesterol concentrations in rats fed a high-cholesterol diet. The Journal of Nutrition 129(9):1705-1712.
Crossref

 
 

Yoshimura T, Inokuchi Y, Mutou C, Sakurai T, Nagahama T, Murakami S (2021). Age-related decline in the taurine content of the skin in rodents. Amino Acids 53(3):429-434.
Crossref

 
 

Zeng DS, Gao ZH, Huang XL, Zhao JH, Huang GQ, Duo L (2012). Effect of taurine on lipid metabolism of broilers. Journal of Applied Animal Research 40(2):86-89.
Crossref

 
 

Zhang L, Wang Y, Sohail T, Kang Y, Niu H, Sun X, Ji D, Li Y (2021). Effects of Taurine on Sperm Quality during Room Temperature Storage in Hu Sheep. Animals 11(9):2725.
Crossref

 
 

Zhang M, Shi X, Luo M, Lan Q, Ullah H, Zhang C, Li S, Chen X, Wang Y, Piao F (2021). Taurine ameliorates axonal damage in sciatic nerve of diabetic rats and high glucose exposed DRG neuron by PI3K/Akt/mTOR-dependent pathway. Amino Acids 53(3):395-406.
Crossref

 
 

Zhao H, Qu J, Li Q, Cui M, Wang J, Zhang K, Liu X, Feng H, Chen Y (2018). Taurine supplementation reduces neuroinflammation and protects against white matter injury after intracerebral hemorrhage in rats. Amino Acids 50(3):439-51.
Crossref

 

 

 




          */?>