L-GLUTAMINE SUPPLEMENTATION PROTECTS AGAINST DISRUPTED CARDIAC GLUTATHIONE ANTIOXIDANT DEFENSE AND POOR FETAL OUTCOME FOLLOWING LATE GESTATIONAL TESTOSTERONE EXPOSURE

Abstract

Objective: Gestational testosterone exposure has been linked with low birth weight and the development of cardiometabolic disorders in both the mother as well as offspring. Increase in circulating testosterone has been associated with pregnancy pathologies such as preeclampsia. L-glutamine supplementation in healthy humans has been shown to cause reduction in pro-inflammatory cytokines as well as improve the glutathione antioxidant defenses. However, the effect of L-glutamine on circulating and cardiac inflammation as well as glutathione antioxidant defenses in gestational testosterone-exposed animals is yet to be determined. This study therefore aimed to investigate the effect of L-glutamine supplementation on circulating and cardiac inflammation, oxidative stress, glutathione antioxidant defenses as well as fetal outcome following late gestational testosterone exposure. Design and method: Pregnant Wistar rats were allotted into four groups (n = 6) receiving vehicle (distilled water, p.o and olive oil, s.c), testosterone (0.5 mg/kg body weight s.c), L-glutamine (1 g/kg body weight p.o) or a combination of testosterone and L-glutamine between gestational days 15 and 19. Results: The findings of this study shows that late gestational testosterone exposure led to an increase in circulating and cardiac inflammatory (adenosine deaminase, xanthine oxidase, uric acid) and oxidative stress (lactate dehydrogenase, malondialdehyde) markers as well as a disruption in the circulating and cardiac glutathione antioxidant defenses (glutathione, glutathione peroxidase, glutathione disulfide and glucose-6-phosphate dehydrogenase) and fetal outcome (fetal weight and number of pups). However, supplementation with L-glutamine led to a reduction of the gestational testosterone-induced increase in circulatory and cardiac inflammatory and oxidative stress markers. L-glutamine supplementation also improved the testosterone-induced disrupted circulating and cardiac glutathione antioxidant defenses as well as the fetal outcome. Conclusions: The findings of this study demonstrate that supplementation with L-glutamine prevents disruption of the glutathione antioxidant defenses and poor fetal outcome associated with late gestational testosterone exposure. This was accompanied by an improvement in the inflammatory and oxidative stress profile of these animals.