Open AccessInfluence of Timing of Administration of Liposome‐encapsulated Superoxide Dismutase on Its Prevention of Acetaminophen‐induced Liver Cell Necrosis in Rats
Author(s) -
Nakae Dai,
Yoshiji Hitoshi,
Yamamoto Kazuhiko,
Maruyama Hiroshi,
Kinugasa Tetsuo,
Takashima Yoshinori,
Denda Ayumi,
Konishi Yoichi
Publication year - 1990
Publication title -
acta patholigica japonica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
ISSN - 0001-6632
DOI - 10.1111/j.1440-1827.1990.tb01601.x
Subject(s) - acetaminophen , oxidative stress , pharmacology , superoxide dismutase , necrosis , toxicity , in vivo , liver injury , chemistry , medicine , toxin , biochemistry , biology , microbiology and biotechnology
The possible participation of acute oxidative stress in the in vlvo mechanism by which acetaminophen (APAP) induces hepatocellular injury was examined. Male Sprague‐Daw‐ley 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 aminotrans‐ferases 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.