title: Haematotoxic and reproductive toxicity of fixed dose combined anti-tuberculous agents: protective role of antioxidants in rats.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The study is aimed to determine the reproductive and haematological toxicity of combined antituberculous agents and the modulatory role of antioxidants using animal model.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Vitamins C and E positively modulated the sperm quality and haematological damage produced by the Fixed Dose Combined Anti-Tuberculous agents.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Lagos, Lagos, Nigeria. awodeleo@yahoo.com
authors.forename: O
authors.initials: O
authors.lastname: Awodele
authors.affiliation: Department of Haematology, College of Medicine, University of Lagos, Lagos, Nigeria.
authors.forename: V O
authors.initials: VO
authors.lastname: Osunkalu
authors.affiliation: Department of Pharmacology, College of Medicine, University of Lagos, Lagos, Nigeria.
authors.forename: I A
authors.initials: IA
authors.lastname: Adejumo
authors.affiliation: Department of Pharmacology, College of Medicine, University of Lagos, Lagos, Nigeria.
authors.forename: A A
authors.initials: AA
authors.lastname: Odeyemi
authors.affiliation: Department of Biochemistry, College of Medicine, University of Lagos, Lagos, Nigeria.
authors.forename: O A T
authors.initials: OA
authors.lastname: Ebuehi
authors.affiliation: Department of Pharmacology, College of Medicine, University of Lagos, Lagos, Nigeria.
authors.forename: A
authors.initials: A
authors.lastname: Akintonwa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001835:Body Weight; D004338:Drug Combinations; D004912:Erythrocytes / Q000187:drug effects*; D006403:Hematologic Tests; D006454:Hemoglobins / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D013094:Spermatozoa / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D000995:Antitubercular Agents; D004338:Drug Combinations; D006454:Hemoglobins; D014810:Vitamin E; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D001205:Ascorbic Acid