On the protective effect of omega-3 against propionic acid-induced neurotoxicity in rat pups.

BACKGROUNDS: The investigation of the environmental contribution for developmental neurotoxicity is very important. Many environmental chemical exposures are now thought to contribute to the development of neurological disorders, especially in children. Results from animal studies may guide investigations of human populations toward identifying environmental contaminants and drugs that produce or protect from neurotoxicity and may help in the treatment of neurodevelopmental disorders. OBJECTIVE: To study the protective effects of omega-3 polyunsaturated fatty acid on brain intoxication induced by propionic acid (PPA) in rats. METHODS: 24 young male Western Albino rats were enrolled in the present study. They were grouped into three equal groups; oral buffered PPA-treated group given a nuerotoxic dose of 250 mg/Kg body weight/day for 3 days; omega-3 - protected group given a dose of 100 mg/kg body weight/day omega-3 orally daily for 5 days followed by PPA for 3 days, and a third group as control given only phosphate buffered saline. Tumor necrosis factor-α, caspase-3, interlukin-6, gamma amino-buteric acid (GABA), serotonin, dopamine and phospholipids were then assayed in the rats brain's tissue of different groups. RESULTS: The obtained data showed that PPA caused multiple signs of brain toxicity as measured by depletion of gamaaminobyteric acid (GABA), serotonin (5HT) and dopamine (DA) as three important neurotransmitters that reflect brain function. A high significant increase of interlukin-6 (Il-6), tumor necrosis factor-α (TNF-α) as excellent markers of proinflammation and caspase-3 as a proapotic marker were remarkably elevated in the intoxicated group of rats. Moreover, brain phospholipid profile was impaired in PPA-treated young rats recording lower levels of phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylcholine (PC). CONCLUSIONS: Omega-3 fatty acids showed a protective effects on PPA - induced changes in rats as there was a remarkable amelioration of most of the measured parameters (i.e. higher GABA, 5HT, DA, PE, PS and PC) and lower Il-6, TNF-α and caspase-3.

The neurotoxic effect of clindamycin - induced gut bacterial imbalance and orally administered propionic acid on DNA damage assessed by the comet assay: protective potency of carnosine and carnitine.

BACKGROUND: Comet assay is a quick method for assessing DNA damage in individual cells. It allows the detection of single and double DNA strand breaks, which represent the direct effect of some damaging agents. This study uses standard comet quantification models to compare the neurotoxic effect of orally administered propionic acid (PA) to that produced as a metabolite of bacterial overgrowth induced by clindamycin. Additionally, the protective effect of carnosine and carnitine as natural dietary supplements is assessed. METHODS: Single cell gel electrophoresis (comet assays) were performed on brain cortex and medulla samples after removal from nine groups of hamsters including: a control (untreated) group; PA-intoxicated group; clindamycin treated group; clindamycin-carnosine group and; clindamycin-carnitine group. RESULTS: There were significant double strand breaks recorded as tail length, tail moment and % DNA damage in PA and clindamycin-treated groups for the cortex and medulla compared to the control group. Neuroprotective effects of carnosine and carnitine were observed. Receiver Operating Characteristics curve (ROC) analysis showed satisfactory values of sensitivity and specificity of the comet assay parameters. CONCLUSION: Percentage DNA damage, tail length, and tail moment are adequate biomarkers of PA neurotoxicity due to oral administration or as a metabolite of induced enteric bacterial overgrowth. Establishing biomarkers of these two exposures is important for protecting children's health by documenting the role of the imbalance in gut microbiota in the etiology of autism through the gut-brain axis. These outcomes will help efforts directed at controlling the prevalence of autism, a disorder recently related to PA neurotoxicity.