The effect of co-administration of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rat liver


BOZCAARMUTLU A., Sapmaz C., BOZDOĞAN Ö., Kukner A., KILINÇ L., KAYA S. T., ...More

DRUG AND CHEMICAL TOXICOLOGY, vol.45, no.3, pp.990-998, 2022 (SCI-Expanded)

  • Publication Type: Article / Article
  • Volume: 45 Issue: 3
  • Publication Date: 2022
  • Doi Number: 10.1080/01480545.2020.1802475
  • Journal Name: DRUG AND CHEMICAL TOXICOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Environment Index, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.990-998
  • Keywords: Cytochrome P450, diabetes, berberine, glibenclamide, resveratrol, xenobiotic metabolizing enzyme, IN-VITRO, OXIDATIVE STRESS, CYTOCHROME-P450 2E1, MAHONIA-AQUIFOLIUM, ANTIOXIDANT, EXPRESSION, CATALASE, EXTRACT, CELLS, BIOTRANSFORMATION
  • Akdeniz University Affiliated: Yes

Abstract

It is possible to use plant-derived antioxidant molecules in the form of dietary supplements. However, dietary supplement-drug interaction pattern has not been well defined for most of these products. The aim of this study was to determine the effects of berberine, resveratrol, and glibenclamide on xenobiotic metabolizing enzyme activities in diabetic rats. Streptozotocin was administered to create experimental diabetes. Resveratrol (5 mg/kg) (R), glibenclamide (5 mg/kg) (G), and berberine (10 mg/kg) (B) were administered individually or in combinations in DMSO by intraperitoneal administration route to the diabetic rats. DMSO was also given to non-diabetic control (C) and diabetic control (D) groups. Livers of rats were taken under anesthesia at the end of the treatment period (12 days). Ethoxyresorufin O-deethylase (EROD), pentoxyresorufin O-depentylase (PROD), aniline 4-hydroxylase (A4H), erythromycin N-demethylase (ERND), glutathione S-transferase (GST), catalase (CAT), and glutathione reductase (GR) activities were measured in microsomes and cytosols. In addition, histomorphological studies were also performed in the liver tissues. EROD activity of D+R was significantly higher than C and D+R+B. PROD activity of D+R was significantly higher than C, D, D+R+G, D+R+B, and D+R+B+ G. PROD activity of D+B was significantly higher than C and D+R+B. ERND activity of D+R was significantly higher than D+R+G and D+R+B. GST activity of D+R was significantly higher than D+R+G. CAT activity of D+B was significantly lower than C. It is clear that co-administration of resveratrol, berberine, and glibenclamide modifies some of the important xenobiotic metabolizing enzyme activities. Resveratrol and berberine have the potential to cause dietary supplement-drug interaction.