Abstract
Summary The direct effects by in vivo administered DPPD on hepatic microsomal enzyme activities have been investigated with the aim to elucidate the mechanism of protection by this compound against toxic liver injuries. The efficiency of hepatic drug metabolizing system has been evaluated both in vitro and in vivo . Furthermore, liver necrosis (serum GPT activity) was estimated in rats poisoned with carbon tetrachloride after DPPD treatment. The administration of DPPD lowers down the activity of liver aminopyrine demethylase and enlarges the hexobarbital sleeping time. CCl 4 alone inhibits the microsomal enzymes, while a preliminary treatment with DPPD fails in preventing but renders more remarkable the block induced by the halogenoalkane. However, the antioxidant completely protects against liver necrosis in CCl 4 -poisoned rats. These findings support the hypothesis that the biological activities of DPPD can be mediated also by inhibition of drug metabolizing enzymes bound to the endoplasmic reticulum.
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