Raza H, Ahmed I, Lakhani M S, Sharma A K, Pallot D, Montague W
Department of Biochemistry, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates.
Biochem Pharmacol. 1996 Nov 22;52(10):1639-42. doi: 10.1016/s0006-2952(96)00526-6.
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 (CYP) and glutathione S-transferase (GST) drug-metabolizing enzymes in the streptozotocin (STZ)-induced diabetic rat. Hepatic CYP contents, ethoxycoumarin-O-deethylase (ECOD), ethoxyresorufin-O-deethylase (EROD), aniline hydroxylase (AH), and aminopyrene N-demethylase (APD) activities were measured in control, diabetic, and karela juice fed animals. Diabetic rats exhibited a 50-100% increase in AH and EROD activities that was reversed by karela juice feeding. In addition, a decrease (17-20%) in the activities of APD and ECOD was observed in diabetic rat liver. Feeding of karela juice to the diabetic animals brought the level of APD close to that of control animals, while ECOD was further reduced to 60% of the control value. The cytosolic glutathione concentration was decreased in diabetic rats, and karela juice feeding normalized the effect. However, an increase (of 20-30%) in the GST activity was observed in both diabetic and karela juice fed rats. Western immunoblot analysis of CYP and GST isozymes exhibited a differential response during diabetes. The expression of CYP1A1, 2B1, 2E1, 3A4, and 4A2 in diabetes, while a decrease in GST mu was observed. Our results suggest that the changes in hepatic phase I and phase II drug-metabolizing enzyme activities in the STZ-induced diabetic animals may be associated with the altered expression of different CYP and GST isozymes. In addition, we have also observed that karela does not always reverse the effects on drug-metabolizing enzymes in STZ-induced diabetes.
苦瓜（Momordica charantia），俗称卡瑞拉，据报道具有降血糖、抗病毒、抗糖尿病和抗肿瘤活性。在本研究中，我们研究了给链脲佐菌素（STZ）诱导的糖尿病大鼠口服卡瑞拉果汁对肝脏细胞色素P450（CYP）和谷胱甘肽S-转移酶（GST）药物代谢酶的影响。在对照、糖尿病和饮用卡瑞拉果汁的动物中测量了肝脏CYP含量、乙氧基香豆素-O-脱乙基酶（ECOD）、乙氧基试卤灵-O-脱乙基酶（EROD）、苯胺羟化酶（AH）和氨基芘N-脱甲基酶（APD）活性。糖尿病大鼠的AH和EROD活性增加了50-100%，饮用卡瑞拉果汁后这种增加得到逆转。此外，在糖尿病大鼠肝脏中观察到APD和ECOD活性降低（17-20%）。给糖尿病动物喂食卡瑞拉果汁使APD水平接近对照动物，而ECOD进一步降至对照值的60%。糖尿病大鼠的胞质谷胱甘肽浓度降低，喂食卡瑞拉果汁使这种影响恢复正常。然而，在糖尿病大鼠和饮用卡瑞拉果汁的大鼠中均观察到GST活性增加（20-30%）。对CYP和GST同工酶的Western免疫印迹分析显示糖尿病期间有不同的反应。糖尿病时CYP1A1、2B1、2E1、3A4和4A2表达增加，而GSTμ减少。我们的结果表明，STZ诱导的糖尿病动物肝脏I相和II相药物代谢酶活性的变化可能与不同CYP和GST同工酶表达的改变有关。此外，我们还观察到卡瑞拉并不总是能逆转STZ诱导的糖尿病对药物代谢酶的影响。
