Hepatocyte responses to volatile anesthetics: changes in surface scanning and enzyme leakage.
The effects of volatile anesthetics were assessed in freshly isolated rat hepatocytes by surface-scanning electron microscopy and by measuring leakage of cellular enzymes, lactate dehydrogenase and beta-glucuronidase into the surrounding medium. The order of potency in regard to their capacity to produce alterations of these parameters was halothane = methoxyflurane greater than ether = control. The extent of enzyme leakage from hepatocytes exposed to halothane or methoxyflurane was both dose dependent and, for the first 30 minutes, time dependent. Surface scanning of the isolated hepatocytes showed that both halothane and methoxyflurane produced enzyme leakage and morphologic changes in cellular membranes, but ether did not. These studies demonstrate that scanning electron microscopy and enzyme leakage from cells are useful for the evaluation of drug-induced changes in lever cells in vitro. The relation between these drug-induced changes and clinical hepatotoxicity remains to be elucidated.
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002469:Cell Separation; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology; D005019:Ethyl Ethers / Q000633:toxicity*; D005966:Glucuronidase / Q000378:metabolism*; D006221:Halothane / Q000633:toxicity*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008297:Male; D008722:Methods; D008733:Methoxyflurane / Q000633:toxicity*; D008855:Microscopy, Electron, Scanning; D051381:Rats
D005019:Ethyl Ethers; D008733:Methoxyflurane; D007770:L-Lactate Dehydrogenase; D005966:Glucuronidase; D006221:Halothane