Ethambutol-induced ovarian, uterine and placental oxidative stress: Implication for reproductive outcome in female Wistar rats

Abstract

Tuberculosis is a major global challenge, potentially infecting more individuals than other pathogens. Ethambutol, a first line drug used in tuberculosis treatment, lacks adequate research regarding its impact on female reproductive health. This study investigates ethambutol-induced oxidative stress to the ovary, uterus and placenta with implications to reproductive outcome in female Wistar rats. Twenty adult female Wistar rats weighing between 170g-190g were divided into two groups (A and B) of ten rats each. Group A served as control and received only food and water ad libitum. Group B was administered with 15 mg/kg body weight of ethambutol, orally, daily for 28 days. After 28 days, five animals from each group were sacrificed by cervical dislocation and the ovaries and uterus were harvested for oxidative stress analysis. The remaining animals from each group were mated, and ethambutol administration continued until gestational day 19 when they were sacrificed, and the placentae were harvested for oxidative stress analysis. The fetuses were used to study pregnancy outcomes. From the result, ovarian glutathione peroxidase was significantly elevated, uterine superoxide dismutase and catalase levels were significantly decreased while malondialdehyde activity was significantly elevated, placental catalase activity was significantly decreased while glutathione peroxidase and malondialdehyde activities was significantly elevated following ethambutol administration. On pregnancy outcomes, ethambutol significantly decreased crown rump length, litter weight, placental weight and fetal/placental weight ratio. In conclusion, evidence from this study suggests that ethambutol is toxic to the ovary, uterus and placenta via mechanisms that involve oxidative stress resulting in poor pregnancy outcomes.