Toxicity of D-galactosamine for rat hepatocytes in monolayer culture.
Hepatocellular injury was induced by exposure of primary cultures of rat hepatocytes to 4 mM D-galactosamine. The cell damage was very similar to that seen in vivo and in the isolated perfused rat liver, both in biochemical and in structural terms. The severity of the lesions caused by D-galactosamine was dependent on the age of the culture being treated. Less severe damage was found with older cultures. Since the primary metabolic effects of D-galactosamine were age-independent, the reduction in cell damage seems to be due to progressive cell dedifferentiation. Dexamethasone (1 microM) suppressed the full development of the injury, while 1 microM triiodo-L-thyronine enhanced it. A protection of hepatocytes by alpha 2-macroglobulin against the effects of D-galactosamine could be observed neither in vivo nor in vitro. Direct cytotoxic effects of endotoxin from Salmonella minnesota R 595 could be demonstrated only on hepatocytes in the early phases of primary culture using rather high doses of the purified lipopolysaccharide. It is unlikely that they play a major role in the hepatocellular injury seen following endotoxinemia in vivo. Lowering of extracellular Ca2+ concentration and additions of calcium/calmodulin inhibitors did not prevent cell injury after treatment with D-galactosamine. The results suggest that cell death is not due to an increased influx of Ca2+ into the cells.
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Phillips
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Falk
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Decker
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D000418:Albumins / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D003907:Dexamethasone / Q000494:pharmacology; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D005688:Galactosamine / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000418:Albumins; D002147:Calmodulin; D004731:Endotoxins; D014284:Triiodothyronine; D005688:Galactosamine; D003907:Dexamethasone; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D002118:Calcium; D014544:Uridine Triphosphate