Medroxyprogesterone acetate improvement of the hepatic drug-metabolizing enzyme system in rats after chemical liver injury.

Medroxyprogesterone acetate (MPA) has an inducing effect on the hepatic drug-metabolizing enzyme system in the rat. The effect of MPA on the liver metabolism was further evaluated here by investigating the restoration of hepatic function after chemical liver injury in female rats. The hepatic injury was induced by pretreating the animals with CCl4 and dimethylnitrosamine for 4 weeks, after which rats treated with MPA for a week were compared with rats showing spontaneous regeneration upon treatment with the MPA vehicle only. Changes in various parameters of the drug-metabolizing enzyme system were used as indices of hepatic function together with liver protein content. The results showed that MPA therapy increased the cytochrome P-450 content and the activity of NADPH-cytochrome c reductase, the monooxygenase enzymes benzo[a]pyrene hydroxylase and aminopyrine N-demethylase, epoxide hydrolase and glutathione S-transferase. MPA increased the relative values in the rats with liver injury almost equally to, or even more than, that seen in the intact animals in comparison to the corresponding vehicle-treated rats. MPA seemed to enhance protein synthesis during liver regeneration, as indicated by changes in total liver protein and in the gel electrophoresis pattern of the microsomal proteins. The hepatic enzyme induction and enhancement of protein synthesis achieved by MPA after liver injury may be of value in the treatment of liver diseases.