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

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.

Decreasing myocardial estrogen receptors and antioxidant activity may be responsible for increasing ischemia- and reperfusion-induced ventricular arrhythmia in older female rats.

AIMS: This study aimed to investigate the relationship between ischemia- and reperfusion-induced arrhythmia and blood serum estrogen levels, myocardial estrogen receptor levels, antioxidant enzyme activities, and the effects of the estrogen receptor blocker, fulvestrant (ICI 182 780). MAIN METHODS: A total of 102 female Sprague-Dawley rats of different ages (2-3, 6-7, 14-15, and 20-21 months) were used in this study. Myocardial ischemia was produced by ligation of the descending branch of the left anterior descending coronary artery, and reperfusion was produced by releasing this artery. An electrocardiogram (ECG) and blood pressure were recorded for 6 min of ischemia and 6 min of reperfusion. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), estrogen receptor α (ERα), and estrogen receptor ß (ERß) in myocardial tissue and 17 beta-estradiol (E2) in blood serum were measured via enzyme-linked immunosorbent assay (ELISA). The results were compared using a Mann-Whitney U test, one-way analysis of variance (ANOVA), and a student's t-test. KEY FINDINGS: It is not the changes in serum estrogen levels but the decreasing myocardial estrogen receptors and antioxidant activities that could be responsible for the occurrence of more severe arrhythmia in response to reperfusion in older female rats. SIGNIFICANCE: The death rate due to a heart attack in younger men is higher than in women. However, it equalizes after the menopausal stage in women. In this study, the reason for the increasing sudden post-menopausal death rate in women was investigated experimentally.

The protection of resveratrol and its combination with glibenclamide, but not berberine on the diabetic hearts against reperfusion-induced arrhythmias: the role of myocardial KATP channel.

CONTEXT: Cardiovascular dysfunctions such as life-threatening arrhythmias are one of the main reasons of mortality and morbidity in diabetic patients Objective: We aimed to investigate the long-term effects of resveratrol, berberine and glibenclamide combinations on the ischemia/reperfusion (I/R) induced arrhythmias in streptozotocin (STZ)-induced diabetic rats and to investigate the role of myocardial KATP channel in the possible anti-arrhythmic actions of the treatments. METHODS: Two days after induction of diabetes, diabetic rats were treated with resveratrol [5 mg/kg, intraperitoneally (i.p.)], berberine (10 mg/kg, i.p) and glibenclamide (5 mg/kg, i.p) for 6 weeks. On the 43th day, experimental animals were subjected to 6-min ischemia and 6-min reperfusion in vivo. RESULTS: The protein expression of Kir6.2 subunits was downregulated in the diabetic hearts. However, all drug treatments restored the protein expression of Kir6.2 subunits. Resveratrol alone and its combination with glibenclamide decreased the arrhythmia score, the arrhythmic period and the incidence of other types of arrhythmias during the reperfusion period. CONCLUSIONS: The combination of resveratrol with glibenclamide may alleviate reperfusion-induced arrhythmias via an underlying mechanism not be only associated with the restoration of the protein expression of Kir6.2 subunits but also associated with the other subunits or ion channels underlying cardiac action potential.