EFFECT OF BITTER-MELON (MOMORDICA-CHARANTIA) FRUIT JUICE ON THE HEPATIC CYTOCHROME P450-DEPENDENT MONOOXYGENASES AND GLUTATHIONE S-TRANSFERASES IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

Bitter melon (Momordica charantia), commonly known as karela, has been reported to have hypoglycemic, antiviral, antidiabetic, and antitumor activities; In the present study, we have investigated the effects of oral feeding of karela fruit juice on the hepatic cytochrome P450 (CY P) and glutathione S-transferase (GST) drug-metabolizing enzymes in th e streptozotocin (STZ)-induced diabetic rat. Hepatic CYP contents, eth oxycoumarin-O-deethylase (ECOD), ethoxyresorufin-O-deethylase (EROD), aniline hydroxylase (AH), and aminopyrene N-demethylase (APD) activiti es were measured in control, diabetic, and karela juice fed animals. D iabetic rats exhibited a 50-100% increase in AH and EROD activities th at was reversed by karela juice feeding. In addition, a decrease (17-2 0%) in the activities of APD and ECOD was observed in diabetic rat liv er. Feeding of karela juice to the diabetic animals brought the level of APD close to that of control animals, while ECOD was further reduce d to 60% of the control value. The cytosolic glutathione concentration was decreased in diabetic rats, and karela juice feeding normalized t he effect. However, an increase (of 20-30%) in the GST activity was ob served in both diabetic and karela juice fed rats. Western immunoblot analysis of CYP and GST isozymes exhibited a differential response dur ing diabetes. The expression of CYP1Al, 2B1, 2E1, 3A4, and 4A2 was app arently increased in the diabetic rat liver. The expression of GST alp ha and pi appeared to be increased in diabetes, while a decrease in GS T mu was observed. Our results suggest that the changes in hepatic pha se I and phase II drug-metabolizing enzyme activities in the STZ-induc ed diabetic animals may be associated with the altered expression of d ifferent CYP and GST isozymes. In addition, we have also observed that karela does not always reverse the effects on drug-metabolizing enzym es in STZ-induced diabetes. Copyright (C) 1996 Elsevier Science Inc.