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Modulation of xenobiotic metabolism and oxidative stress in chronic streptozotocin-induced diabetic rats fed withMomordica charantia fruit extract

2000; Wiley; Volume: 14; Issue: 3 Linguagem: Inglês

10.1002/(sici)1099-0461(2000)14

1099-0461

Haider Raza, I. Ahmed, Annie John, Ashutosh Sharma,

Drug Transport and Resistance Mechanisms

Journal of Biochemical and Molecular ToxicologyVolume 14, Issue 3 p. 131-139 Modulation of xenobiotic metabolism and oxidative stress in chronic streptozotocin-induced diabetic rats fed with Momordica charantia fruit extract Dr. Haider Raza, Corresponding Author Dr. Haider Raza [email protected] Department of Biochemistry Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates Tel: (9713) 7039 506; Fax: (9713) 672 033Department of Biochemistry Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates Tel: (9713) 7039 506; Fax: (9713) 672 033.Search for more papers by this authorIjaz Ahmed, Ijaz Ahmed Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab EmiratesSearch for more papers by this authorAnnie John, Annie John Department of Biochemistry Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates Tel: (9713) 7039 506; Fax: (9713) 672 033Search for more papers by this authorAshutosh K. Sharma, Ashutosh K. Sharma Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab EmiratesSearch for more papers by this author Dr. Haider Raza, Corresponding Author Dr. Haider Raza [email protected] Department of Biochemistry Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates Tel: (9713) 7039 506; Fax: (9713) 672 033Department of Biochemistry Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates Tel: (9713) 7039 506; Fax: (9713) 672 033.Search for more papers by this authorIjaz Ahmed, Ijaz Ahmed Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab EmiratesSearch for more papers by this authorAnnie John, Annie John Department of Biochemistry Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates Tel: (9713) 7039 506; Fax: (9713) 672 033Search for more papers by this authorAshutosh K. Sharma, Ashutosh K. Sharma Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab EmiratesSearch for more papers by this author First published: 25 February 2000 https://doi.org/10.1002/(SICI)1099-0461(2000)14:3 3.0.CO;2-QCitations: 83AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract We studied the long-term effects of streptozotocin-induced diabetes on tissue-specific cytochrome P450 (CYP) and glutathione-dependent (GSH-dependent) xenobiotic metabolism in rats. In addition, we also studied the effect of antidiabetic Momordica charantia (karela) fruit-extract feeding on the modulation of xenobiotic metabolism and oxidative stress in rats with diabetes. Our results have indicated an increase (35–50%) in CYP4A-dependent lauric acid hydroxylation in liver, kidney, and brain of diabetic rats. About a two-fold increase in CYP2E-dependent hepatic aniline hydroxylation and a 90–100% increase in CYP1A-dependent ethoxycoumarin-O-deethylase activities in kidney and brain were also observed. A significant increase (80%) in aminopyrene N-demethylase activity was observed only in rat kidney, and a decrease was observed in the liver and brain of diabetic rats. A significant increase (77%) in NADPH-dependent lipid peroxidation (LPO) in kidney of diabetic rats was also observed. On the other hand, a decrease in hepatic LPO was seen during chronic diabetes. During diabetes an increased expression of CYP1A1, CYP2E1, and CYP4A1 isoenzymes was also seen by Western blot analysis. Karela-juice feeding modulates the enzyme expression and catalytic activities in a tissue- and isoenzyme-specific manner. A marked decrease (65%) in hepatic GSH content and glutathione S-transferase (GST) activity and an increase (about two-fold) in brain GSH and GST activity was observed in diabetic rats. On the other hand, renal GST was markedly reduced, and GSH content was moderately higher than that of control rats. Western blot analyses using specific antibodies have confirmed the tissue-specific alterations in the expression of GST isoenzymes. Karela-juice feeding, in general, reversed the effect of chronic diabetes on the modulation of both P450-dependent monooxygenase activities and GSH-dependent oxidative stress related LPO and GST activities. 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