The involvement of endotoxin in halothane-associated liver injury.
Since endotoxin, lipopolysaccharides (LPS), have been implicated as a causative factor in the development of hepatic necrosis in rats exposed to hepatotoxic levels of several chemical agents, the role of LPS in the halothane-hypoxia (HH) model of hepatic damage in male Sprague-Dawley rats was investigated. When injected intravenously immediately after halothane anesthesia, a subnecrotic dose of LPS (0.5 mg/kg; Escherichia coli 026:B6) was found to markedly potentiate HH-induced hepatic necrosis. Pretreatment of the animals with the antiendotoxin agent, lactulose, prior to exposure to halothane reduced the hepatic damage normally seen from HH. A possible mechanism of LPS-induced potentiation was indicated by changes in hepatic calcium levels at 24 h after treatment. Endogenous LPS may play a role in HH-induced hepatic necrosis, and the mechanism of LPS-induced potentiation may be due to an LPS-related membrane dysfunction.
D000758:Anesthesia / Q000009:adverse effects; D000818:Animals; D002118:Calcium / Q000032:analysis; D002244:Carbon / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D004737:Enflurane / Q000494:pharmacology; D006221:Halothane / Q000633:toxicity*; D007792:Lactulose / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000032:analysis / Q000187:drug effects*; D008297:Male; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004731:Endotoxins; D008070:Lipopolysaccharides; D007792:Lactulose; D002244:Carbon; D004737:Enflurane; D002118:Calcium; D006221:Halothane