PROTECTIVE EFFECT OF PHYLLANTHUS-FRATERNUS AGAINST THIOACETAMIDE-INDUCED MITOCHONDRIAL DYSFUNCTION

The effect of administration of thioacetamide on rat liver mitochondri al functions and the protective effect of an aqueous extract of Phylla nthus fraternus against thioacetamide-induced damage were studied. Whe n rats were treated with thioacetamide, the rate of mitochondrial resp iration was decreased significantly with both NAD(+) linked and FAD li nked substrates, and the respiratory control ratio, an index of membra ne integrity and the P/O ratio, a measure of phosphorylation efficienc y, decreased significantly. Also, there was a significant decrease in the activities of NADH dehydrogenase, succinate cytochrome c reductase , and cytochrome oxidase; whereas succinate dehydrogenase was not affe cted. A significant decrease was seen in membrane potential and in the lever of mitochondrial ATP. There was a significant decrease in the l evels of phosphatidylcholine, phosphatidylethanolamine, and cardiolipi n by thioacetamide treatment. The lipid peroxide level increased signi ficantly in thioacetamide-treated rats. Administration of P. fraternus prior to thioacetamide treatment relieved the inhibition of all the p arameters studied, and brought down the lipid peroxide levels signific antly in liver homogenates and mitochondria. This study shows that P. fraternus protects against thioacetamide-induced toxicity by its abili ty to suppress the elevated lipid peroxide levels in the mitochondrial membrane.