Awodele O, Momoh A A, Awolola N A, Kale O E, Okunowo W O
Department of Pharmacology, Therapeutics and Toxicology, College of Medicine, PMB 12003, Idi-Araba Campus, University of Lagos, Nigeria.
Department of Anatomic and Molecular Pathology, College of Medicine, Idi-Araba Campus, University of Lagos, Nigeria.
Toxicol Rep. 2016 Jul 19;3:620-627. doi: 10.1016/j.toxrep.2016.06.007. eCollection 2016.
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.
在大鼠中评估了固定剂量一线抗结核联合(CFDAT)方案的生殖毒性。32只体重为168.1±8.0克的Wistar大鼠被分为四组,每组8只。两组雄性和雌性大鼠分别口服蒸馏水(1.6毫升)和含有利福平、异烟肼、吡嗪酰胺和乙胺丁醇的CFDAT药物(RIPE,每体表面积92.5毫克/平方米),持续45天。治疗后的雄性大鼠血清促卵泡激素、黄体生成素和睾酮显著降低(p<0.05)。同样,与对照组相比,精子计数水平下降了27.3%。RIPE提高了治疗后雌性大鼠的血清雌激素(p<0.05)、孕酮(p<0.05)以及催乳素(p>0.05)水平。此外,RIPE降低了雄性动物而非雌性动物的总蛋白水平,并增加了(p<0.05,53%)过氧化氢酶水平。超氧化物歧化酶、谷胱甘肽-S-转移酶、谷胱甘肽过氧化物酶、还原型谷胱甘肽水平以及脂质过氧化在所有大鼠中均未改变。组织病理学研究显示,与对照组相比,睾丸周围血管充血,卵巢无变化。总体而言,我们的结果证明了RIPE在大鼠中的生殖毒性潜力,因此,建议在抗结核化疗期间监测这些生殖参数。