Inhibition of lipid peroxidation by disulfiram and diethyldithiocarbamate does not prevent hepatotoxin-induced cell death in isolated rat hepatocytes. A study with allyl alcohol, tert-butyl hydroperoxide, diethyl maleate, bromoisovalerylurea and carbon tetrachloride.
The relationship between lipid peroxidation and cell death, induced by a number of hepatotoxins, was studied in isolated rat hepatocytes. Disulfiram (DSF) and diethyldithiocarbamate (DDC) completely prevented lipid peroxidation, induced by allyl alcohol, tert-butyl hydroperoxide (t-BHP), diethyl maleate (DEM), bromoisovalerylurea (BIU) and carbon tetrachloride (CCl4). Lipid peroxidation was measured by the formation of both thiobarbituric acid positive material and conjugated dienes. However, DSF and DDC did not protect against cell death, induced by these hepatotoxins. In the presence of DSF or DDC, cell death occurred even earlier in time. We conclude that cell death can occur in the absence of lipid peroxidation. Therefore, lipid peroxidation is not a requisite for the induction of cell death.
Dogterom
P
P
Division of Toxicology, University of Leiden, The Netherlands.
Nagelkerke
J F
JF
van Steveninck
J
J
Mulder
G J
GJ
D000433:1-Propanol / Q000494:pharmacology; D000818:Animals; D001968:Bromisovalum / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004221:Disulfiram / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology*; D005260:Female; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008298:Maleates / Q000494:pharmacology; D010545:Peroxides / Q000494:pharmacology; D020005:Propanols; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D008054:Lipid Peroxides; D008298:Maleates; D010545:Peroxides; D020005:Propanols; D014810:Vitamin E; C006463:allyl alcohol; D001968:Bromisovalum; D020122:tert-Butylhydroperoxide; D000433:1-Propanol; D004050:Ditiocarb; D002251:Carbon Tetrachloride; C014476:diethyl maleate; D004221:Disulfiram