Neuroprotective effect of creatine against propionic acid toxicity in neuroblastoma SH-SY5Y cells in culture

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.Keywords: Propionic acid, creatine, SH-SY5Y, comet assay, DNA fragmentation assay, apoptosis, neuroprotection.African Journal of Biotechnology Vol. 12(31), pp. 4925-493

Mechanism of nitrogen metabolism-related parameters and enzyme activities in the pathophysiology of autism

<p>Abstract</p> <p>Background</p> <p>There is evidence that impaired metabolism play an important role in the etiology of many neuropsychiatric disorders. Although this has not been investigated to date, several recent studies proposed that nitrogen metabolism-related parameters may have a pathophysiological role in autism.</p> <p>Methods</p> <p>The study enrolled 20 Saudi boys with autism aged 4 to 12 years and 20 healthy controls matched for age and gender. Levels of creatine, urea, ammonia, gamma-aminobutyric acid (GABA), glutamate:glutamine (Glu:Gln) ratio, and enzymatic activities of glutamate dehydrogenase, 5'-nucleotidase, and adenosine deaminase (ADA) were determined in plasma samples from both groups.</p> <p>Results</p> <p>We found a significant elevation of creatine, 5'-nucleotidase, GABA, and glutamic acid and a significant decrease in the enzymatic activity of ADA and glutamine level in patients with autism compared with healthy controls. The most significant variation between the two groups was found in the Glu:Gln ratio.</p> <p>Conclusion</p> <p>A raised Glu:Gln ratio together with positive correlations in creatine, GABA, and 5'-nucleotidase levels could contribute to the pathophysiology of autism, and might be useful diagnostic markers. The mechanism through which these parameters might be related to autism is discussed in detail.</p