Abstract

This work aimed to verify propionic acid toxic effects, and to investigate the possible neuroprotective effects of creatine against it. Propionic acid (PA) toxicity together with the effect of creatine (CR) was studied on neuroblastoma SH-SY5Y brain cells in culture. In the first group, cells were divided and treated with different concentrations of PA, while the second group was pre-treated with creatine to test its neuroprotective effect in PA-intoxicated cells. Comet assay and DNA fragmentation studies were used to examine genotoxicity and apoptosis of cells. The results emphasized the neurotoxicity of propionate to neuroblastoma cell line SH-SY5Y by DNA fragmentation that increased in a dose- and time-dependent manner. More importantly, our data confirms a possible neuroprotective effect of creatine against the neurotoxic effect of propionic acid. The obtained in vitro data supports and explains the in vivo neurotoxic effect of PA and proves its DNA damaging effect which could clarify its role in the etiology of autism, a phenomenon recently raised by many researchers. It also supported the accumulating literature which describes creatine as a potential bioactive agent against neurotoxicity. With sufficient research and clinical trials in future, this could prove to be successful in treatment or management of autism as a neurodevelopmental disorder recently related to PA neurotoxicity.

Key words: Propionic acid, creatine, SH-SY5Y, comet assay, DNA fragmentation assay, apoptosis, neuroprotection.