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.
Highlights
Propionic acid (PA) is a short chain fatty acid that is dietary obtained (Zarate et al, 2004), or naturally produced in cellular metabolism (Thompson et al, 1990)
Our results show increased DNA fragmentation in the PA-treated cells compared to control, which was clearly evident in the comet assay data and was supported by the DNA fragmentation ladder results
After 48 h (Figure 2), the tail length for cells treated with 5mM PA increased more (3.525 μm), compared to the 24 h results (2.442 μm) and control (0.781 μm), with the same observation in those treated with the higher PA dose
Summary
Propionic acid (PA) is a short chain fatty acid that is dietary obtained (Zarate et al, 2004), or naturally produced in cellular metabolism (Thompson et al, 1990). PA is thought to be involved in behavioral and neuropathological abnormalities reported in some neurological conditions (Wajner et al, 2004). The chemical properties of this weak acid facilitate its easy access to the brain; where it can accumulate, leading to intracellular acidification (Bonnet et al, 2000). These facts sugges that central nervous system (CNS) is sensitive to high PA levels (Brusque et al, 1999). Rodevelopmental metabolic disorder, characterized by elevated PA accompanied by developmental delay and various neurological and behavioral manifestations (Feliz et al, 2003). PA neurotoxicity develops from consequent alterations at many levels, like metabolism (Brass and Beyerinck 1988), inflammatory response (Cavaglieri et al, 2003), and neurotransmission (Cannizzaro et al, 2003)
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