The combined fixed-dose antituberculous drugs alter some reproductive functions with oxidative stress involvement in wistar rats

Abstract

The reproductive toxicity of combined fixed-dose first-line antituberculosis (CFDAT) regimen was assessed in rats. Thirty-two (32) Wistar rats weighing 168.1 ± 8.0 g were divided into four groups of eight rats per group. Two groups of male and female rats were administered oral distilled water (1.6 ml) and CFDAT drugs containing rifampicin, isoniazid, pyrazinamide and ethambutol (RIPE, 92.5 mg/m2 per body surface area) respectively for forty-five days. Serum follicle stimulating hormone, luteinizing and testosterone were reduced significantly (p < 0.05) in the treated male rats. Similarly, sperm count levels were decreased by 27.3% when compared with control. RIPE elevated serum oestrogen (p < 0.05), progesterone (p < 0.05) as well as prolactin (p > 0.05) levels in the treated females. In addition, RIPE reduced (p < 0.05) total proteins levels and increased (p < 0.05, 53%) catalase levels in male but not female animals. Superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, reduced glutathione levels as well as lipid peroxidation were unaltered in all rats respectively. Histopathological studies revealed congested peritesticular vessels and no changes in the ovary when compared with control. Overall, our results demonstrate reproductive toxicity potentials of RIPE in the rat, thus, suggesting that these reproductive parameters be monitored during antituberculous chemotherapy.

The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice

“…The observation of the effect of the FDC is similar to those of Awodele et al (2016) wherein they observed alteration of reproductive hormones in male and female rats when compared to the NC groups. Rifampicin is associated with hepatotoxicity mediated by oxidative damage ( Shanker et al, 2005 ; Chowdhury et al, 2006 ).…”

“…Congestion of blood vessels suggests that the anti-TB drugs may have impaired venous outflow in the mice testes and thus, resulted in congestion. Awodele et al (2016) attributed decreased sperm counts and motility to choked vessels in the peri-testicular and Leydig cells of the stroma in the testes of rats exposed to the FDC and was linked to a reduction in male fertility. Testicular degeneration involves a retrogressive change in the germinal epithelium of the seminiferous tubules ( Macfarlane et al, 2001 ).…”

“…The histological and genotoxic changes in the testicular cells of the treated mice could have been due to the ability of metabolites of the anti-TB medications to cross the blood testes barrier ( Shayakhmetova et al, 2012 ; Awodele et al, 2016 ). Apart from the possible action of each of the individual drugs, and their metabolites, it may be assumed that oxidative stress is part of the causative mechanisms ( Shayakhmetova et al, 2012 ; Shayakhmetova et al, 2016 ).…”

Safety evaluation of Bon-santé cleanser ® polyherbal in male Wistar rats: Further investigations on androgenic and toxicological profile

“… 54 , 55 Also, studies of positive stimulation by FSH and LH, which agreed with local paracrine signalling, have been reported. 54 , 56 This may, in part help maintains oestrogen secretion by the dominant follicle and thus, may provide such suitability for BSC to also be investigated in female species.…”

Impact of the Anti-Tuberculosis Drug Rifampicin on the Feeding, Growth and Embryonic Developmental Profile of the Mosquitofish <i>Gambusia affinis</i>

“…Our knowledge of the effect of RIF on reproduction and embryonic development is confined to only mammals, and these effects are equivocal in both male and female rats. The combined treatment of RIF with other anti-TB drugs such as ethambutol, isoniazid, and pyrazinamide in male rats causes an increase in oxidative damage with consequent suppression of the fertility index and lowers serum levels of Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), and testosterone associated with lower sperm counts 18,19 . Similarly, RIF treatment reduces the quality of sperm chromatin structure and motility 20 , but increases testosterone levels in male rats by stimulating the production of 17-hydroxylase in the testes 21 .…”