Abstract

This study aimed to compare the neuroprotective potency of carnosine and carnitine supplements against the proinflammatory and prooxidant effects of orally administrated propionic acid and clindamycin induced changes in microflora of hamsters. Nine experimental groups, each consisting of six young male golden Syrian hamsters were investigated: control group (received only phosphate buffered saline), oral buffered PA-treated group (received a neurotoxic dose of 250 mg/kg  PA for three days),  oral clindamycin-treated group (received a single dose of 30 mg clindamycin/kg),  oral carnosine-treated group received a daily  dose of 10 mg/kg/day  for one week, oral carnitine-treated group was given a daily oral dose of 50 mg/kg/day  for one week, and four protected groups received the same doses of carnosine or carnitine for one week followed by PA for 3 days or a single dose of clindamycin. Interferonγ (INF-γ), heat shock protein (HSP70), malondialdehyde (MD), and glutathione peroxidase (GPX) were measured in the cortexes and medullas at the end of the experiment. This study confirmed the pro-inflammatory and pro-oxidant effects of orally administered PA and overgrowth of pathogenic bacteria in hamsters.  While PA induced a significant increase of IFN-γ, HSP70, and MD with a significant decrease of GPX activity in brain cortex and medulla, clindamycin brought a marked increase only in MD and HSP70 with a reduction of GPX activity. Receiver operating characteristics (ROC) analysis showed satisfactory specificity and sensitivity which could help to suggest that the measured parameters could be used as brain injury biomarkers. Although bacterial overgrowth induced by clindamycin was effective in inducing signs of neuronal toxicity in cortex and medulla, its effect were not comparable to those induced by the oral administration of PA. The findings suggest that the overgrowth of specific bacteria does not manifest significant neurologic harms until there is toxic exposure to a dietary metabolite.

Key words: Autism, propionic acid, clindamycin, oxidative stress, pro-inflammation, bacterial overgrowth