Awodele O, Osunkalu V O, Adejumo I A, Odeyemi A A, Ebuehi O A T, Akintonwa A
Department of Pharmacology, College of Medicine, University of Lagos, Lagos, Nigeria.
Department of Haematology, College of Medicine, University of Lagos, Lagos, Nigeria.
Nig Q J Hosp Med. 2013 Jan-Mar;23(1):17-21.
Tuberculosis (TB) is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV/AIDS. The major problem militating against the management of tuberculosis is the lack of compliance to medication by the infected patients as a result of multidrug needed to be taking daily leading to resistance. Occurrences of hepatic toxicity, teratogenicity, sperm quality damage, haematotoxicity and meningeal congestion of individual anti-tuberculous agents have been reported.
The study is aimed to determine the reproductive and haematological toxicity of combined antituberculous agents and the modulatory role of antioxidants using animal model.
Fifty rats (10 per group) were randomly allotted to five groups, consisting of the control, the fixed dose combined anti TB agents treated group, the fixed dose combined anti TB agents plus vitamin C treated group, the fixed dose combined anti TB agents plus vitamin E treated group and the fixed dose combined anti TB agents plus vitamin C plus vitamin E treated group. Therapeutic doses of the fixed dose combined anti TB agents (25 mg/kg/day), vitamin E (5 mg/kg) and vitamin C (8 mg/kg) were administered to the animals via oral gavage, daily over 28 days. After 28days, rats were sacrificed for internal macroscopic and histological examination of the organs, sperm analysis and haematological investigations were carried out.
The results showed a significant increase (p < or = 0.05) in the levels of white blood cells (WBC), red blood cell (RBC) and haemoglobin (HB) of the combined anti-TB plus vitamins C or E treated groups compared with combined anti-TB treated group alone (56.34 +/- 0.11) that decreased the haematological parameters. A significant decrease (p < or = 0.05) in the sperm counts (22.26 +/- 0.02; 35.40 +/- 0.02) and motility (77.03 +/- 0.02; 94.50 +/- 0.01) of the combined anti-TB treated rats as compared with the control group were observed. The combined anti-TB plus vitamin C treated rats demonstrated a significant increase (p < or = 0.05) in the sperm motility (90.23 +/- 0.01) as compared with the control group. There was also a remarkable decrease in the abnormal morphology of the sperm in the combined anti-TB plus vitamins E and C treated rats (0.05 +/- 0.02) as compared with the combined anti-TB group alone (1.10 +/- 0.02).
Vitamins C and E positively modulated the sperm quality and haematological damage produced by the Fixed Dose Combined Anti-Tuberculous agents.
结核病是全球育龄女性最大的传染性杀手，也是艾滋病毒/艾滋病患者的主要死因。影响结核病治疗的主要问题是，由于需要每日服用多种药物，受感染患者对药物治疗的依从性差，从而导致耐药性。已有报告指出，个别抗结核药物会出现肝毒性、致畸性、精子质量损害、血液毒性和脑膜充血等情况。
本研究旨在使用动物模型确定联合抗结核药物的生殖和血液毒性以及抗氧化剂的调节作用。
将50只大鼠（每组10只）随机分为五组，包括对照组、固定剂量联合抗结核药物治疗组、固定剂量联合抗结核药物加维生素C治疗组、固定剂量联合抗结核药物加维生素E治疗组以及固定剂量联合抗结核药物加维生素C加维生素E治疗组。通过口服灌胃法，每日给动物施用固定剂量联合抗结核药物（25毫克/千克/天）、维生素E（5毫克/千克）和维生素C（8毫克/千克）的治疗剂量，持续28天。28天后，处死大鼠，对器官进行内部宏观和组织学检查，并进行精子分析和血液学研究。
结果显示，与单独使用联合抗结核药物治疗组（56.34±0.11）相比，联合抗结核药物加维生素C或E治疗组的白细胞（WBC）、红细胞（RBC）和血红蛋白（HB）水平显著升高（p≤0.05），而单独使用联合抗结核药物治疗组的血液学参数有所下降。与对照组相比，可以观察到联合抗结核药物治疗的大鼠精子数量（22.26±0.02；35.40±0.02）和活力（77.03±0.02；94.50±0.01）显著下降。与对照组相比，联合抗结核药物加维生素C治疗的大鼠精子活力显著提高（p≤0.05）（90.23±0.01）。与单独使用联合抗结核药物组（1.10±0.02）相比，联合抗结核药物加维生素E和C治疗的大鼠精子异常形态也显著减少（0.05±0.02）。
维生素C和E对固定剂量联合抗结核药物所产生的精子质量和血液损害具有积极的调节作用。
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