Protection by Osbeckia aspera against carbon tetrachloride-mediated alterations in microsomal drug metabolizing enzyme activity

Previous investigations have confirmed the protective effect of Osbeckia as pera leaf extract on carbon tetrachloride-mediated liver injury in rat mode ls. It is well known that the earliest alterations in liver cell structure and function following carbon tetrachloride poisoning involve the endoplasm ic reticulum and its drug metabolizing enzymes. Therefore, we investigated whether an aqueous leaf extract of O. aspera could offer protection against carbon tetrachloride-induced changes in the microsomal drug metabolizing e nzymes aniline hydroxylase and p-aminopyrine N-demethylase. This enzyme act ivity was compared with phenobarbital-induced righting reflex and lipid per oxidation. Treatment of rats with the aqueous leaf extract of O. aspera (before or aft er the administration of carbon tetrachloride) resulted in a marked decreas e in carbon tetrachloride-mediated alterations in aniline hydroxylase and p -aminopyrine N-demethylase activity, phenobarbital-induced loss of righting reflex and malondialdehyde formation due to lipid peroxidation. The K-m va lue of these enzymes in control and Osbeckia-treated rats were the same. These results show that the plant extract can markedly decrease the carbon tetrachloride-mediated reduction in aniline hydroxylase and p-aminopyrine N -demethylase activity and inhibit peroxidative damage to the cell membrane. Phenobarbital-induced sleeping time in rats and kinetic enzyme studies sug gested that the effects of the plant extract was neither due to an inductio n of the drug-metabolizing enzymes under investigation, nor due to an alter ation in the K-m values of these enzymes.