SODIUM ACETATE ATTENUATES MYOCARDIAL TRIGLYCERIDE ACCUMULATION IN COMBINED ORAL CONTRACEPTIVE-TREATED RATS BY SUPPRESSING ADENOSINE DEAMINASE/XANTHINE OXIDASE-DEPENDENT PATHWAY

Abstract

Objective: Myocardial triglyceride accumulation characterizes many cardiovascular disorders. Cardiovascular disorders are the leading cause of mortality and morbidity worldwide. Continuous usage of Combined Oral Contraceptive (COC) has been associated with disrupted lipid metabolism, however, the exact mechanism is not clear. Adenosine Deaminase (ADA) and Xanthine Oxidase (XO) are reportedly involved in cardiometabolic derangement, particularly lipid dysmetabolism. We, therefore hypothesized that increased ADA and XO activities and elevated uric acid level are involved in COC-induced myocardial triglyceride accumulation. This study also aimed at investigating the ameliorative effects of sodium acetate on COC-induced myocardial lipid accumulation in female Wistar rats. Design and method: Female Wistar rats received vehicle per ostium (p.o.) and COC (1.0 microgram of ethinylestradiol plus 5.0 microgram of levonorgestrel; p.o.) with or without sodium acetate (ACE; 200 miligram/kilogram; p.o.) for 8 weeks (n = 6/group). Insulin resistance was estimated by homeostatic model of assessment whereas glucose tolerance was determined by oral glucose tolerance test. Other biochemical variables were evaluated using standard methods. Data were analysed using one-way analysis of variance followed by Bonferroni's post hoc test. Significant differences were accepted at p < 0.05. Results: Treatment with COC led to increased 1-h postload glucose response, plasma insulin, triglyceride-glucose index, insulin resistance and impaired glucose tolerance. COC treatment also resulted in increased plasma and cardiac free fatty acid, triglyceride, triglyceride/high density lipoprotein-cholesterol ratio, malondialdehyde, uric acid, ADA and XO activities. On the other hand, COC led to reduction in nitric oxide level. However, sodium acetate significantly ameliorated the alterations induced by COC treatment, but XO activity remains elevated during COC treatment. Conclusions: Therefore, sodium acetate would impact positively on myocardial lipid accumulation-related cardiovascular disorders, at least in part, by suppression of adenosine deaminase/xanthine oxidase/uric acid-dependent pathway.