title: Influence of timing of administration of liposome-encapsulated superoxide dismutase on its prevention of acetaminophen-induced liver cell necrosis in rats.
abstract: The possible participation of acute oxidative stress in the in vivo mechanism by which acetaminophen (APAP) induces hepatocellular injury was examined. Male Sprague-Dawley rats were administered 3-methylcholanthrene, fasted for 18 h, then given APAP and sacrificed after a further 6 h of fasting. Extensive centrilobular liver cell necrosis along with markedly elevated serum activity of aminotransferases was observed. Liposome-encapsulated human recombinant Cu-Zn superoxide dismutase (LSOD) administered 1 or 0.5 h prior to APAP or simultaneously with the toxin completely prevented APAP-induced hepatocellular injury. In contrast, LSOD administered 5 or 2.5 h before or 1, 2.5 or 5 h after the toxin treatment did not prevent APAP toxicity. Incomplete protection against APAP-induced injury was obtained when LSOD was administered 0.5 h after the toxin. These results support the proposal of an oxidative mechanism for APAP hepatotoxicity.
authors.affiliation: Department of Oncological Pathology, Nara Medical University, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Nakae
authors.forename: H
authors.initials: H
authors.lastname: Yoshiji
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Maruyama
authors.forename: T
authors.initials: T
authors.lastname: Kinugasa
authors.forename: Y
authors.initials: Y
authors.lastname: Takashima
authors.forename: A
authors.initials: A
authors.lastname: Denda
authors.forename: Y
authors.initials: Y
authors.lastname: Konishi
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000818:Animals; D004337:Drug Carriers; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009336:Necrosis / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000008:administration & dosage*; D013997:Time Factors; D000637:Transaminases / Q000097:blood
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D000082:Acetaminophen; D013482:Superoxide Dismutase; D000637:Transaminases