Journal of Cancer Research and Experimental Oncology
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Article Number - 9DAF62446732


Vol.6(2), pp. 20-28 , March 2014
DOI: 10.5897/JCREO2013.0105
ISSN: 2141-2243



Full Length Research Paper

Effects of omega-3 fatty acids against Ehrlich carcinoma-induced hepatic dysfunction



Ussama Z. Said
  • Ussama Z. Said
  • National Center for Radiation Research and Technology, Atomic Energy Authority (AEA), Egypt.
  • Google Scholar
Neamat H. Ahmed
  • Neamat H. Ahmed
  • National Center for Radiation Research and Technology, Atomic Energy Authority (AEA), Egypt.
  • Google Scholar
Amina M. Medhat
  • Amina M. Medhat
  • Faculty of Science, Ain Shams University, Cairo, Egypt.
  • Google Scholar
Mustafa M. Mustafa
  • Mustafa M. Mustafa
  • National Center for Radiation Research and Technology, Atomic Energy Authority (AEA), Egypt.
  • Google Scholar







 Accepted: 26 January 2014  Published: 31 March 2014

Copyright © 2014 Author(s) retain the copyright of this article.
This article is published under the terms of the Creative Commons Attribution License 4.0


Omega-3 essential fatty acids (ω-3 FATs); found in the highest concentrations in fish oil, claim a plethora of health benefits. The present study aims to evaluate the biological effects of ω-3 FATs supplementation against Ehrlich carcinoma (EC) induced inflammation, oxidative stress, biochemical and histopathological alterations in the liver tissue of albino mouse. ω-3 FATs were orally administered via gavage to mice for a period of 30 consecutive days at a dose of 300 mg/kg body weight. On the 7th day of ω-3 FATs administration, female mice were subcutaneously injected with 0.2 ml of Ehrlich ascite carcinoma for solid tumor induction. The present study revealed that, subcutaneous injection of Ehrlich solid tumor led to hepatic oxidative stress (as significant increase in lipid peroxidation (thiobarbituric acid reactive species, TBARS), concomitant with a significant decrease in glutathione and antioxidant enzymes), systemic inflammation (significant increases in C-reactive protein, tumor necrosis factor-alpha and leukocyte counts) and biochemical alterations (as increase in liver function enzymes)). While in the tumor tissue, significant increase in tumor TBARS content and non significant changes in glutathione and antioxidant enzymes were observed. Histopathological studies showed that EC cells metastasis caused fatty degeneration, enlargement of liver cells nuclei and presence of necrosis. Pretreatment of animals with ω-3 FATs significantly reduced tumor size and markedly improved most of the biochemical parameters associated with the inoculation of EC. It could be concluded that ω-3 FATs administrated to mice, reduce tumor size, inhibit systemic inflammation, improving liver function profile, modulating lipid peroxidation and augmenting antioxidant defense system in EC bearing mice.

 

Key words: Ehrlich carcinoma (EC), omega-3 fatty acids, liver.

An WS, Kim H J, Cho KH, Vaziri ND (2009). Omega-3 fatty acid supplementation attenuates oxidative stress, inflammation, and tubulointerstitial fibrosis in the remnant kidney. Am. J. Physiol. Renal Physiol. 297(4):F895-903.‏
Crossref
 
Avogadri F, Mittal D, Saccheri F, Sarrafiore M, Ciocca M, Larghi P, Orecchia R, Rescigno M (2008). "Intra-Tumoral Salmonella typhimurium Induces a Systemic Anti-Tumor Immune Response That is Directed by Low-Dose Radiation to Treat Distal Disease." Eur. J. Immunol. 38(7):1937-1947.
Crossref
 

Bansal AK, Bansal M, Soni G, Bhatnagar D (2005). Protective role of Vitamin E pre-treatment on N-nitrosodiethylamine induced oxidative stress in rat liver. Chemico-biol. interact. 156(2-3):101-111.‏

Pubmed

 
Bartsch H, Nair J, Owen RW (1999). Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: emerging evidence for their role as risk modifiers. Carcinogenesis 20(12):2209-2218.
Crossref
 
Bazan NG (2007). Omega-3 fatty acids, pro-inflammatory signaling and neuroprotection. Curr. Opin. Clin. Nutr. Metab. Care. 10(2):136-141.‏
Pubmed
 
Beutler E, Duron O, Kelly BM (1963). Improved method for the determination of blood glutathione. J. Lab. Clin. Med. 61:882-888.‏
Pubmed
 
Bhattacharya S, Haldar P (2011). Trichosanthes dioica root extract induces tumor proliferation and attenuation of antioxidant system in albino mice bearing Ehrlich ascites carcinoma. Interdiscip. Toxicol. 4(4):184-190.
Crossref
 
Browning LM (2003). n-3 polyunsaturated fatty acids, inflammation, and obesity-related disease. Proc. Nutr. Soc. 62(2):447-453.
Crossref
 
Deepa PR, Varalakshmi P (2003). Protective effect of low molecular weight heparin on oxidative injury and cellular abnormalities in adriamycin-induced cardiac and hepatic toxicity. Chem. Biol. Interact. 146(2):201-210.
Crossref
 
Duvnjak M, Lerotić I, Baršić N, Tomašić V, Virović Jukić L, Velagić V (2007). Pathogenesis and management issues for non-alcoholic fatty liver disease. World J. Gastroenterol. 13(34):4539-4550.‏
Pubmed
 
Dwivedi S, Sharma A, Patrick B, Sharma R, Awasthi YC (2007). Role of 4-hydroxynonenal and its metabolites in signaling. Redox Rep. 12(1-2):4-10.
Crossref
 
Dyall SC, Michael GJ, Michael‐Titus AT (2010). Omega‐3 fatty acids reverse age‐related decreases in nuclear receptors and increase neurogenesis in old rats. J. Neurosci. Res. 88(10):2091-2102.‏
Crossref
 
El-Gawish M (2003). Antitumor activity of inositol hexaphosphate (Phytic acid) in mice loaded with solid tumor. Egypt. J. Biomed. Sci. 11:106-121.
 
Espada CE, Berra MA, Martinez MJ, Eynard AR, Pasqualini ME (2007). Effect of Chia oil (Salvia hispanica) rich in ω-3 fatty acids on the eicosanoid release, apoptosis and T-lymphocyte tumor infiltration in a marine mammary gland adenocarcinoma. Prostaglandins Leukot. Essent. Fatty Acids 77(1):21-28.
Crossref
 
Fahim FA, Esmat AY, Mady EA, Amin MA (1997). Serum LDH and ALP isozyme activities in mice bearing solid Ehrlich carcinoma and/or treated with maximum tolerated dose (MTD) of aloin. Dis. Markers 13:183-193.
Pubmed
 
Farooqui AA, Horrocks LA, Farooqui T (2007). Modulation of inflammation in brain: a matter of fat. J. Neurochem. 101(3):577-599.‏
Crossref
 
Gross RT, Bracci R, Rudolph N, Schroeder E, Kochen JA (1967). Hydrogen peroxide toxicity and detoxification in the erythrocytes of newborn infants. Blood 29(4):481-493.‏
Pubmed
 
Gupta A, Rosenberger SF, Bowden GT (1999). Increased ROS levels contribute to elevated transcription factor and MAP kinase activities in malignantly progressed mouse keratinocyte cell lines. Carcinogen 20(11):2063-2073.‏
Crossref
 
Gupta M, Mazumder UK, Kumar RS, Sivakumar T, Vamsi MLM (2004). Antitumor activity and antioxidant status of Caesalpinia bonducella against Ehrlich ascites carcinoma in Swiss albino mice. J. Pharmacol. Sci. 94(2):177-184.
Crossref
 

‏Hayashi I, Ohotsuki M, Suzuki I, Watanabe T (2001). Effects of oral administration of Echinacea purpurea (American herb) on incidence of spontaneous leukemia caused by recombinant leukemia viruses in AKR/J mice. Nihon Rinsho Meneki Gakkai Kaishi 24(1):10-20.

Pubmed

 
Kerner A, Avizohar O, Sella R, Bartha P, Zinder O, Markiewicz W, Levy Y, Brook GJ, Aronson D (2005). Association between elevated liver enzymes and C-reactive protein: possible hepatic contribution to systemic inflammation in the metabolic syndrome. Arterioscler. Thromb. Vasc. Biol. 25(1):193-197.
Pubmed
 
Hanson LO (1997). Estimation of C-reactive proteins. Curr. Opin. Infect. Dis. 10:196-201.‏
 
Hu FB (2001). The balance between ω-6 and ω-3 fatty acids and the risk of coronary heart disease. Nutrition 17(9):741-742.‏
Crossref
 
Jia LJ, Xu HM, Ma DY, Hu QG, Huang XF, Jiang WH, Li SF, Jia KZ, Huang QL, Hua ZC (2005). Enhanced therapeutic effect by combination of tumor-targeting Salmonella and endostatin in murine melanoma model. Cancer Biol. Ther. 4(8):840-845.‏
Crossref
 
Judé S, Roger S, Martel E, Besson P, Richard S, Bougnoux P, Le Guennec JY (2006). Dietary long-chain omega-3 fatty acids of marine origin: a comparison of their protective effects on coronary heart disease and breast cancers. Progress Biophys. Mol. Biol. 90(1-3):299-325.‏
Crossref
 
Kalapos MP, Littauer A, qde Groot H (1993). Has reactive oxygen a role in methylglyoxal toxicity? A study on cultured rat hepatocytes. Arch. Toxicol. 67(5):369-372.‏
Crossref
 
Lim K, Han C, Dai Y, Shen M, Wu T (2009). Omega-3 polyunsaturated fatty acids inhibit hepatocellular carcinoma cell growth through blocking β-catenin and cyclooxygenase-2. Mol. Cancer Ther. 8(11):3046-3055.‏
Crossref
 
Manju V, Kalaivani SJ, Nalini N (2002). Circulating lipid peroxidation and antioxidant status in cervical cancer patients: a case-control study. Clin. Biochem. 35(8):621-625.‏
Crossref
 

Maeda H, Akaike T (1998). "Nitric Oxide and Oxygen Radicals in Infection, Inflammation, and Cancer." Biochememistry (Mosc) 63(7):854-865.

Pubmed

 
Majumder S, Dutta P, Mookerjee A, Choudhuri SK (2006). The role of a novel copper complex in overcoming doxorubicin resistance in Ehrlich ascites carcinoma cells in vivo. Chemico-Biol. Interact. 159(2):90-103.
Crossref
 
Mantovani A (2005). Cancer: inflammation by remote control. Nature 435(7043):752-753.
Crossref
 
Marnett LJ (2000). Oxyradicals and DNA damage. Carcinogenesis 21(3):361-370.
Crossref
 
Masayasu M, Hiroshi Y (1979). A simplified assay method of superoxide dismutase activity for clinical use. Clin. Chim. Acta 92(3):337-342.‏
Crossref
 
Oberley TD (2002). Oxidative damage and cancer. Am. J. Pathol. 160(2):403-408.
Crossref
 
O'Byrne KJ, Dalgleish AG (2001). Chronic immune activation and inflammation as the cause of malignancy. Br. J. Cancer. 85:473-483.
Crossref
 
Patyar S, Joshi R, Byrav DSP, Prakash A, Medhi B, Das BK (2010). Review Bacteria in cancer therapy: a novel experimental strategy. J. Biomed. Sci. 17(1):21.
Crossref
 
Philip M, Rowley DA, Schreiber H (2004). Inflammation as a tumor promoter in cancer induction. Semin. Cancer Biol. 14(6):433-439.
Crossref
 
Anand P, Kunnumakkara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB (2008). Cancer is a Preventable Disease that Requires Major Lifestyle Changes. Pharm. Res. 25(9):2097-2116.
Crossref
 
Raso GM, Pacilio M, di Carlo G, Esposito E, Pinto L, Meli R (2002). In- vivo and in‐vitro anti‐inflammatory effect of Echinacea purpurea and Hypericum perforatum. J. Pharm. Pharmacol. 54(10):1379-1383.‏
Crossref
 
Roy AV (1970). Rapid method for determining alkaline phosphatase activity in serum with thymolphthalein monophosphate. Clin. Chem. 16(5):431-436.‏
Pubmed
 
Ruka W, Rutkowski P, Kaminska J, Rysinska A, Steffen J (2001). Alterations of routine blood tests in adult patients with soft tissue sarcomas: Relationships to cytokine serum levels and prognostic significance. Ann. Oncol. 12(10):1423-1432.
Crossref
 

Sakr SA, Mahran HA, Lamfon HA (2011). "Protective Effect of Ginger (Zingiber officinale) on Adriamycin-Induced Hepatotoxicity in Albino Rats." J. Med. Plant Res. 5(1):133-140.

View

 

Sawyer MB, Field CJ (2010). Possible mechanisms of ω-3 PUFA anti-tumor action. In: Calviello G, Serini S (eds.) Dietary omega-3 polyunsaturated fatty acids and cancer. Diet Cancer 1:3-38.

View

 
Schottenfeld D, Beebe-Dimmer J (2006). Chronic Inflammation: A Common and Important Factor in the Pathogenesis of Neoplasia. CA Cancer J. Clin. 56(2):69-83.
Crossref
 
Sinha AK (1972). Colorimetric assay of catalase. Analyt. Biochem. 47(2):389-394.‏
Crossref
 
Sun SY, Li W, Yue P, Lippman SM, Hong WK, Lotan R (1999). Mediation of N-(4-hydoxyphenyl) retinamide-induced apoptosis in human cancer cells by different mechanisms. Cancer Res. 59(10):2493-2498.‏
Pubmed
 
Szymczak M, Murray M, Petrovic N (2008). "Modulation of angiogenesis by ω-3 polyunsaturated fatty acids is mediated by cyclooxygenases". Blood 111(7):3514-3521.‏
Crossref
 
Takada Y, Ichikawa H, Badmaev V, Aggarwal BB (2006). Acetyl-11-keto-β-boswellic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing NF-κB and NF-κB-regulated gene expression. J. Immunol. 176(5):3127-3140.‏
Pubmed
 
Tibaldi C, Vasile E, Bernardini I, Orlandini C, Andreuccetti M, Falcone A (2008). Baseline elevated leukocyte count in peripheral blood is associated with poor survival in patients with advanced non-small cell lung cancer: a prognostic model. J. Cancer Res. Clin. Oncol. 134(10):1143-1149.
Crossref
 
Vincent PC, Nicholls A (1967). Comparison of the growth of the Ehrlich ascites tumor in male and female mice. Cancer Res. 27(6 Part 1):1058-1065.‏
Pubmed
 
Wang M, Liu YE, Ni J, Aygun B, Goldberg ID, Shi YE (2000). Induction of mammary differentiation by mammary-derived growth inhibitorrelated gene that interacts with an omega-3 fatty acid on growth inhibition of breast cancer cells. Cancer Res. 60(22):6482-6487.
Pubmed
 
Yamamoto T, Hsu S, Lewis J, Wataha J, Dickinson D, Singh B, Bollag WB, Lockwood P, Ueta E, Osaki T, Schuster G (2003). Green tea polyphenol causes differential oxidative environments in tumor versus normal epithelial cells. J. Pharmacol. Exp. Ther. 307(1):230-236.‏
Crossref
 
Yoshioka T, Kawada K, Shimada T, Mori M (1979). Lipid peroxidation in maternal and cord blood and protective mechanism against activated-oxygen toxicity in the blood. Am. J. Obstet. Gynecol. 135(3):372-376.‏
Pubmed
 
Young DS, Friedman RB (2001). Effects of Disease on Clinical Laboratory Tests, 4th edition. American Association for Clinical Chemists‏ Press, Washington DC.

 


APA Said, U.Z., Ahmed, N.A., Medhat, A.M., & Mustafa, M.M. (2014). Effects of omega-3 fatty acids against Ehrlich carcinoma-induced hepatic dysfunction. Journal of Cancer Research and Experimental Oncology, 6(2), 20-28.
Chicago Ussama Z. Said, Neamat H. Ahmed, Amina M. Medhat and Mustafa M. Mustafa. "Effects of omega-3 fatty acids against Ehrlich carcinoma-induced hepatic dysfunction." Journal of Cancer Research and Experimental Oncology 6, no. 2 (2014): 20-28.
MLA Ussama Z. Said, et al. "Effects of omega-3 fatty acids against Ehrlich carcinoma-induced hepatic dysfunction." Journal of Cancer Research and Experimental Oncology 6.2 (2014): 20-28.
   
DOI 10.5897/JCREO2013.0105
URL http://academicjournals.org/journal/JCREO/article-abstract/9DAF62446732

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