MATERNAL ESTROGEN-PROGESTIN IMPROVES CARDIAC GLUCOSE-6-PHOSPHATE DEHYDROGENASE ACTIVITY BUT AGGRAVATES TRIGLYCERIDE IN GESTATIONAL GLUCOCORTICOID-EXPOSED RATS

Abstract

Objective: Glucocorticoids (GCs) are used in pregnant women to treat numerous medical disorders. Oral estrogen-progestin, a means of contraception that has been associated with cardiometabolic disturbances is widely used as a method of maternal contraception. We therefore sought to investigate the effects of maternal COC on dams that were exposed to late gestational GC. Design and method: Twenty-four female rats were mated to achieve timed pregnancy and delivery. They were randomly allotted into 4 groups of 6 rats each. Dams received COC (combination of 1.0 microgram ethinylestradiol and 5.0 microgram levonorgestrel) between 3rd and 11th week maternal with or without prior exposure to GC (dexamethasone; 0.2 mg/kg) between gestational days 14–19. Plasma corticosterone and insulin were determined by using ELISA. Triglyceride (TG), was measured by standardized enzymatic colorimetric method. Plasma and cardiac levels of glucose-6-phosphate dehydrogenase (G6PD), nicotinamide adenine dinucleotide phosphate (NADPH), oxidized glutathione (GSSG), reduced glutathione (GSH), glutathione peroxidase (GPx), xanthine oxidase (XO), adenosine deaminase (ADA), uric acid, FFA, lactate, lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were measured by spectrophotometric method using assay kit Results: Data showed that late-gestational GC exposure led to insulin resistance (IR), increased cardiac ADA, XO, lactate, LDH, and disrupted cardiac G6PD-dependent antioxidant defenses. On the other hand, maternal COC treatment in dams not exposed to gestational GC led to IR, increased cardiac XO, LDH and defective cardiac G6PD-dependent antioxidant defenses. However, maternal COC with prior gestational GC exposure led to attenuated IR, cardiac ADA, UA, LDH, and improved cardiac G6PD-dependent antioxidant defenses but worsened cardiac TG accumulation when compared with dam with gestational GC exposure without maternal COC. Circulating corticosterone was comparatively elevated in the three experimental groups compared to dam without prior GC exposure and maternal COC treatment. Conclusions: The result provides evidence that late gestational GC exposure programs IR that is accompanied with increased ADA, lactate production and defective cardiac G6PD-dependent antioxidant defense, whereas maternal COC use resulted in IR and defective cardiac G6PD-dependent antioxidant defense. The study further suggests that maternal COC improves GC-programmed cardiovascular risk factors with enhanced cardiac TG accumulation.