The first line anti-tuberculosis (anti-TB) drugs; isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and pyrazinamide (PZA) were effective in the treatment of pulmonary tuberculosis. However, the toxicity of these drugs has been of great concern in clinical settings. This study was designed to evaluate the toxic effects of anti-TB drugs on reproductive system in female rats. Thirty-five female Wistar rats were assigned into five groups of seven animals each. The control received normal saline, while others received INH (5 mg/kg), RIF (10 mg/kg), EMB (15 mg/kg) and PZA (15 mg/kg) via gavage thrice in a week for eight consecutive weeks. Results showed that anti-TB drugs significantly (P< 0.05) reduced both uterine and ovarian weights, and relative weight of uterus relative to controls. In addition, anti-TB drugs increased the activities of alanine aminotransferase (ALT) and levels of total bilirubin. Furthermore, treatment with INH, RIF and PZA significantly (P<0.05) reduced the levels of luteinizing hormone, estrogen and prolactin. In contrast, there were no significant differences (P>0.05) in the levels of follicle stimulating hormone and progesterone in rats treated with anti-TB drugs when compared to controls. Moreso, INH, RIF, EMB and PZA caused significant (P<0.05) increase in the uterine malondialdehyde (MDA) levels by 281, 214, 273 and 190%, respectively, while INH and EMB increased the ovarian MDA levels by 111% and 129%, respectively. All the anti-TB drugs significantly (P< 0.05) decreased the activities of ovarian glutathione-S-transferase and uterine glutathione peroxidase, superoxide dismutase and catalase. Histopathological examinations showed severe erosion of uterine mucosa, cellular debris in lumen of uterus and under-developed follicles in ovary of the rats. These results confirmed that the first line anti-TB drugs elicited reproductive toxicity in female rats via mechanism that involved oxidative stress.
20 - 23 May 2017
European Society of Endocrinology