title: Therapeutic effect of liposomal-N-acetylcysteine against acetaminophen-induced hepatotoxicity.
abstract: BACKGROUND
  Acetaminophen (APAP) is an antipyretic analgesic drug that when taken in overdose causes depletion of glutathione (GSH) and hepatotoxicity. N-acetylcysteine (NAC) is the antidote of choice for the treatment of APAP toxicity; however, due to its short-half-life repeated dosing of NAC is required.
  
  
  OBJECTIVE
  To determine whether a NAC-loaded liposomal formulation (Lipo-NAC) is more effective than the conventional NAC in protecting against acute APAP-induced hepatotoxicity.
  
  
  METHODS
  Male Sprague-Dawley rats were challenged with an intragastric dose of APAP (850 mg/kg b.wt.); 4 h later, animals were administered saline, NAC, Lipo-NAC or empty liposomes and sacrificed 24 h post-APAP treatment.
  
  
  RESULTS
  APAP administration resulted in hepatic injury as evidenced by increases in plasma bilirubin, alanine (AST) and aspartate (ALT) aminotransferase levels and tissue levels of lipid peroxidation and myeloperoxidase as well as decreases in hepatic levels of reduced GSH, GSH peroxidase and GSH reductase. Treatment of animals with Lipo-NAC was significantly more effective than free NAC in reducing APAP-induced hepatotoxicity. Histological evaluation showed that APAP caused periacinar hepatocellular apoptosis and/or necrosis of hepatocytes around the terminal hepatic venules which was reduced by NAC treatment, the degree of reduction being greater for Lipo-NAC.
  
  
  CONCLUSIONS
  These data suggest that administration of Lipo-NAC ameliorated the APAP-induced hepatotoxicity.
authors.affiliation: Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University, Thunder Bay, ON P7B 5E1, Canada.
authors.forename: Misagh
authors.initials: M
authors.lastname: Alipour
authors.forename: Caroline
authors.initials: C
authors.lastname: Buonocore
authors.forename: Abdelwahab
authors.initials: A
authors.lastname: Omri
authors.forename: Mary
authors.initials: M
authors.lastname: Szabo
authors.forename: Kresimir
authors.initials: K
authors.lastname: Pucaj
authors.forename: Zacharias E
authors.initials: ZE
authors.lastname: Suntres
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D000111:Acetylcysteine / Q000737:chemistry / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008081:Liposomes; D000082:Acetaminophen; D009195:Peroxidase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D001663:Bilirubin; D000111:Acetylcysteine