肠道菌群紊乱和闭症4.docVIP

肠道菌群紊乱和自闭症4 Gut?Pathog.?2013 Apr 12;5(1):9. doi: 10.1186/1757-4749-5-9. 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. El-Ansary A1,?Shaker GH,?El-Gezeery AR,?Al-Ayadhi L. Author information 1Department of Biochemistry, College of Science, King Saud University, P,O Box 22452, Riyadh 11495, Saudi Arabia. elansary@ksu.edu.sa. Abstract 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