title: Hepatoprotective role of neutrosecR on hepatic damage induced by combination of zidovudine and combined anti-tuberculous agents in rats.
abstract: BACKGROUND
  Advent of the HIV/AIDS pandemic has led to a dramatic increase in the number of TB cases worldwide. Availability of highly active antiretroviral therapy (HAART) has significantly improved the outcome of HIV/AIDS, in terms of prevention of opportunistic infections (OIs) as well as mortality however; liver toxicity is one of the most relevant adverse effects of antiretroviral therapy (ART).
  
  
  OBJECTIVE
  In view of the inevitable use of zidovudine (a common ART) and antituberculous fixed-dose combination therapy (FDCs) in the management of HIV-TB co-infection and the resultant hepatotoxicity, this study was aimed to investigate the hepatoprotective role of neutrosec (a combination of aminoacid and vitamins) on the hepatotoxicity induced by co-administration of zidovudine and combined fixed dose antituberculous agents.
  
  
  METHODS
  Twenty four rats were randomly allotted to four groups, consisting of the control, zidovudine plus fixed dose combined anti TB agents treated group, zidovudine plus fixed dose combined anti TB agents plus neutrosec treated group and neutrosec alone treated group. Therapeutic doses of zidovudine (8.5 mg/kg/day), fixed dose combined anti TB agents (25 mg/kg/day) and neutrosec (0.4 ml/kg/day) were administered to the animals via oral gavage, daily over 60 days. After 60 days, rats were sacrificed for internal macroscopic and histological examination of the liver. The liver enzyme parameters (AST, ALP, Total bilirubin, Total protein, Albumin) were determined using fully automated clinical chemistry analyzer (Hitachi 912, Boehringer Mannheim, Germany). Antioxidant enzymes activity and lipid peroxidation were determined according to standard procedures.
  
  
  RESULTS
  The AST results showed a significant (p ≤ 0.05) decreased in the zidovudine plus anti-TB plus neutrosec treated group (125.50 ± 22.71) compared with zidovudine plus anti-TB treated group (399. 10 ± 0.45). It further showed non-significant decreased (p ≥ 0.05) in the ALP levels between the zidovudine plus anti TB treated group (317.10 ± 73.48) and the zidovudine plus anti TB plus neutrosec treated group (203.20 ± 35.97). There was a non-significant (p ≤ 0.05) decrease in the MDA level of the zidovudine plus anti-TB plus neutrosec treated group compared with the zidovudine plus anti-TB treated group.
  
  
  CONCLUSIONS
  The hepatotoxic effect of zidovudine plus combined anti TB drugs which may be due to free radical generation was modulated by neutrosec.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Lagos, Nigeria. awodeleo@yahoo.com
authors.forename: Olufunsho
authors.initials: O
authors.lastname: Awodele
authors.forename: Esther O
authors.initials: EO
authors.lastname: Agbaje
authors.forename: Enitan A
authors.initials: EA
authors.lastname: Adesina
authors.forename: Alade
authors.initials: A
authors.lastname: Akintonwa
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D019587:Dietary Supplements; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008111:Liver Function Tests; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D014815:Vitamins / Q000008:administration & dosage / Q000627:therapeutic use*; D015215:Zidovudine / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000596:Amino Acids; D019380:Anti-HIV Agents; D000975:Antioxidants; D000995:Antitubercular Agents; D004338:Drug Combinations; D020011:Protective Agents; D014815:Vitamins; D015215:Zidovudine; D002374:Catalase