title: Ameliorative Effects of Kolaviron, a Biflavonoid Fraction from Garcinia Kola Seed, on Hepato-renal Toxicity of Anti-tuberculosis Drugs in Wistar Rats.
abstract: BACKGROUND
  Tuberculosis (TB) is an infectious disease of international health priority. The combination of anti-TB drugs (4-Tabs)- isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (ETB) are effective in the management of the disease, however, their toxic effect is a major concern.
  
  
  OBJECTIVE
  The study was designed to evaluate the toxicity of anti-TB drugs in male Wistar rats and possible ameliorative effects of kolaviron (KV), a biflavonoid from Garcinia kola seeds.
  
  
  METHODS
  Twenty-eight rats were assigned into four groups; Group 1 (Control) received corn oil, Group 2 (4-Tabs) received therapeutic doses of INH (5 mg/kg), RIF (10 mg/kg), PZA (15 mg/kg) and ETB (15 mg/kg) in combination, Group 3 (4-Tabs + KV) received INH, RIF, PZA, ETB and KV (200 mg/kg) and Group 4 (KV) received KV (200 mg/kg) by oral gavage three times per week for 8 consecutive weeks.
  
  
  RESULTS
  Administration of 4-Tabs caused oxidative stress resulting in significant (p = 0.031, 0.027) increase in malondialdehyde levels in the liver and kidney of rats by 101% and 34%, respectively. Also, 4-Tabs caused significant (p = 0.023-0.035) elevation of serum alanine and aspartate aminotransferases by 41% and 48%, creatinine by 252% and total bilirubin by 89%, respectively. In contrast, hepatic and renal antioxidant indices- reduced glutathione, glutathione peroxidase, glutathione-s-transferase and superoxide dismutase were significantly (p = 0.028-0.039) decreased in 4-Tabs-treated rats. Co-administration of KV with 4-Tabs significantly restored the antioxidant parameters and biochemical indices to near normal.
  
  
  CONCLUSIONS
  These findings suggest that anti-TB drugs elicit oxidative damage in liver and kidney of rats while KV protects against the adverse effects via antioxidative mechanism.
authors.affiliation: Department of Biochemistry, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, Oyo, State, Nigeria. aoadaramoye@yahoo.com.
authors.forename: Oluwatosin A
authors.initials: OA
authors.lastname: Adaramoye
authors.forename: Aderemi O
authors.initials: AO
authors.lastname: Kehinde
authors.forename: Adedoyin
authors.initials: A
authors.lastname: Adefisan
authors.forename: Olugbenga
authors.initials: O
authors.lastname: Adeyemi
authors.forename: Idowu
authors.initials: I
authors.lastname: Oyinlola
authors.forename: Olubukola O
authors.initials: OO
authors.lastname: Akanni
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000633:toxicity*; D001219:Aspartate Aminotransferases; D004977:Ethambutol / Q000009:adverse effects / Q000633:toxicity; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D029763:Garcinia kola / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D007538:Isoniazid / Q000009:adverse effects / Q000633:toxicity; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011718:Pyrazinamide / Q000009:adverse effects / Q000633:toxicity; D017208:Rats, Wistar; D012293:Rifampin / Q000009:adverse effects / Q000633:toxicity; D012639:Seeds / Q000737:chemistry
chemical_list: D000975:Antioxidants; D000995:Antitubercular Agents; D005419:Flavonoids; D011718:Pyrazinamide; D008315:Malondialdehyde; D004977:Ethambutol; D005979:Glutathione Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; C045492:kolaviron; D007538:Isoniazid; D012293:Rifampin