Extracellular calcium alleviates cell toxicity due to hepatotoxins that induce lipid peroxidation, but has no effect on toxins that do not cause lipid peroxidation. A study in isolated rat hepatocytes.
The effect of extracellular calcium on cell death, induced by hepatotoxins that induce lipid peroxidation [diethyl maleate (DEM), allyl alcohol (AA) and bromoisovalerylurea (BIU)] and hepatotoxins that do not induce lipid peroxidation [disulfiram (DSF), N-hydroxy-2-acetyl-aminofluorene (N-OH-AAF) and tetrahydroaminoacridine (THA)] was studied in freshly isolated rat hepatocytes. Extracellular calcium strongly delayed the onset of toxicity of DEM, AA and BIU as detected by lipid peroxidation, depletion of free protein thiol groups and cell death. This protective effect of calcium was decreased at higher concentrations of the toxic compounds. In contrast, no effect of calcium was observed on toxicity induced in the absence of lipid peroxidation by DSF, N-OH-AAF and THA. Addition of calcium was also without effect on the protein thiol depletion. These results indicate that calcium only alleviates cytotoxicity which is induced by thiol depletion resulting from lipid peroxidation. Cytotoxicity as a result of protein thiol depletion through disulfide formation is not affected by extracellular calcium.
Dogterom
P
P
Division of Toxicology, University of Leiden, The Netherlands.
Kroese
E D
ED
Mulder
G J
GJ
Nagelkerke
J F
JF
D000433:1-Propanol / Q000494:pharmacology; D000818:Animals; D001968:Bromisovalum / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003603:Cytotoxins / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020005:Propanols; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism
D003603:Cytotoxins; D008054:Lipid Peroxides; D020005:Propanols; D013438:Sulfhydryl Compounds; C006463:allyl alcohol; D001968:Bromisovalum; D000433:1-Propanol; D005978:Glutathione; D002118:Calcium