Reoxygenation injury in rat hepatocytes: mediation by O2/H2O2 liberated by sources other than xanthine oxidase.
The mechanism of reoxygenation injury was studied in primary cultures of isolated hepatocytes from rat liver. Reoxygenation injury, which affected up to 80% of the hepatocytes, was only inducible within a certain time window of the anaerobic incubation. Reintroduction of oxygen before this vulnerable period ensured the survival of the hepatocytes. After the vulnerable period upon reintroduction of oxygen the hepatocytes continued to die in the same way as the anaerobic control. Allopurinol had no effect on reoxygenation injury. From the inhibitors of the mitochondrial respiratory chain, both cyanide and antimycin A increased injury while rotenone was without significant effect on injury. Reoxygenation injury was significantly diminished by superoxide dismutase, but not by catalase. When added together, superoxide dismutase and catalase completely prevented reoxygenation injury. The results demonstrate that reoxygenation injury in hepatocytes is mediated by the combined action of both O2- and H2O2. These reduced oxygen species are not liberated by xanthine oxidase but possibly originate from the mitochondrial respiratory chain.
de Groot
H
H
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf.
Brecht
M
M
D000493:Allopurinol / Q000494:pharmacology; D000693:Anaerobiosis; D000818:Animals; D000968:Antimycin A / Q000633:toxicity; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D003486:Cyanides / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012402:Rotenone / Q000633:toxicity; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism*
D003486:Cyanides; D012402:Rotenone; D000493:Allopurinol; D000968:Antimycin A; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010100:Oxygen