ORAL ETHINYLESTRADIOL-LEVONORGESTREL COUNTERACTS FRUCTOSE IMPACTS ON RENAL METABOLIC FUNCTION IN FEMALE WISTAR RATS

Abstract

Objective: Renal function is critical in the regulation of cardiovascular parameters such as blood pressure and endothelial factors. However, evidence suggests that the excessive intake of fructose (FRU) induces insulin resistance (IR)-associated renal impairment, which perhaps contribute to global increase in cardiovascular disease (CVD). Similarly, the use of estrogen-progestin formulation of oral contraceptive (EEL) has been associated with metabolic disruption with consequent attendant CVD risk factors, and its non-contraceptive benefits especially in metabolic pathologies remain inconclusive. Therefore, the present study was designed to investigate the effects of EEL on renal metabolic function in female rats exposed to high fructose drink. Design and method: Female Wistar rats weighing 140–170 g were randomly allotted into control, EEL, FRU and EEL+FRU groups (6 rats per group). The groups received vehicle (p.o.), EEL containing 1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel (p.o.), fructose (10%; w/v) and EEL plus FRU respectively, daily for 8 weeks. Insulin resistance, pancreatic beta-cell function and insulin sensitivity were estimated by homeostatic model of assessment (HOMA-IR), HOMA-beta and quantitative insulin sensitivity check index (QUICKI) respectively. Plasma and tissue biochemical parameters were determined using enzyme-linked immunosorbent assay kits or fluorescence assay as appropriate. Results: Data revealed that FRU or EEL caused IR, impaired glucose tolerance and hyperinsulinemia with corresponding increase in plasma or renal triglyceride, total cholesterol, atherogenic lipid, xanthine oxidase, uric acid, lactate synthesis, renal glycogen synthesis, decreased plasma or renal adenosine, glucose-6-dehydrogenase (G6PD) and glutathione (GSH). High fructose but not EEL increased plasma glucose, urea and creatinine, plasma or renal gamma-glutamyl transferase, malondialdehyde and decreased plasma or renal NO and pancreatic beta-cell function. Interestingly, these alterations were attenuated when EEL was concomitantly administered with FRU exposure. Conclusions: The results of the study demonstrate that high fructose intake causes renal impairment, attributable to lipid and glycogen deposition, and collectively accompanied by excessive lipid peroxidation, impaired NO/adenosine-dependent endothelial function and defective G6PD/GSH-dependent antioxidant defense. The findings also suggest that EEL blots the renal effects of high fructose by possibly improving insulin sensitivity, endothelial function and antioxidant defense.