title: Effect of adrenergic blockers, carvedilol, prazosin, metoprolol and combination of prazosin and metoprolol on paracetamol-induced hepatotoxicity in rabbits.
abstract: OBJECTIVE
  To evaluate hepatoprotective potential of carvedilol, prazosin, metoprolol and prazosin plus metoprolol in paracetamol-induced hepatotoxicity.
  
  
  METHODS
  Thirty-six male rabbits were divided into six groups, six in each, group 1 received distilled water, group 2 were treated with paracetamol (1 g/kg/day, orally), group 3, 4,5 and 6 were treated at a dose in (mg/kg/day) of the following: Carvedilol (10 mg), prazosin (0.5 mg), metoprolol (10 mg), and a combination of metoprolol (10 mg) and prazosin (0.5 mg) respectively 1 h before paracetamol treatment. All treatments were given for 9 days; animals were sacrificed at day 10. Liver function tests, malondialdehyde (MDA) and glutathione (GSH) in serum and liver homogenates were estimated. Histopathological examinations of liver were performed.
  
  
  RESULTS
  Histopathological changes of hepatotoxicity were found in all paracetamol-treated rabbits. The histopathological findings of paracetamol toxicity disappeared in five rabbits on prazosin, very mild in one. In carvedilol group paracetamol toxicity completely disappeared in three, while mild in three rabbits. Paracetamol hepatotoxicity was not changed by metoprolol. In metoprolol plus prazosin treated rabbits, moderate histopathological changes were observed. Serum liver function tests and MDA in serum and in liver homogenate were elevated; GSH was depleted after paracetamol treatment and returned back to the control value on prior treatment with prazosin. MDA in serum and liver homogenate, alkaline phosphatase, total bilirubin were significantly decreased after carvedilol and prazosin plus metoprolol treatments.
  
  
  CONCLUSIONS
  Carvedilol and prazosin are hepatoprotective in paracetamol hepatotoxicity, combination of prazosin and metoprolol have moderate, and metoprolol has a little hepatoprotection.
authors.affiliation: College of Pharmacy, Department of Pharmacology and Toxicology, Basrah College of Medicine, Basrah, Iraq.
authors.forename: Maysaa B
authors.initials: MB
authors.lastname: Zubairi
authors.affiliation: Department of Pharmacology, Basrah College of Medicine, Basrah, Iraq.
authors.forename: Jawad H
authors.initials: JH
authors.lastname: Ahmed
authors.affiliation: Department of Pathology and Forensic Medicine, Basrah College of Medicine, Basrah, Iraq.
authors.forename: Sawsan S
authors.initials: SS
authors.lastname: Al-Haroon
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D018674:Adrenergic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002227:Carbazoles / Q000494:pharmacology / Q000627:therapeutic use*; D000077261:Carvedilol; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004359:Drug Therapy, Combination; D005978:Glutathione / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D011224:Prazosin / Q000494:pharmacology / Q000627:therapeutic use*; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits
chemical_list: D018674:Adrenergic Antagonists; D002227:Carbazoles; D011412:Propanolamines; D020011:Protective Agents; D000077261:Carvedilol; D000082:Acetaminophen; D008315:Malondialdehyde; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D005978:Glutathione; D008790:Metoprolol; D001663:Bilirubin; D011224:Prazosin
keywords: Antioxidant; carvedilol; liver toxicity; metoprolol; paracetamol; prazosin