Copper toxicity and lipid peroxidation in isolated rat hepatocytes: effect of vitamin E.
We investigated the role of lipid peroxidation as the mechanism mediating copper toxicity in isolated rat hepatocytes and the modulating effect of vitamin E. Hepatocytes, isolated from rats fed diets containing deficient (E-), sufficient (E+), and excess (E++) amounts of vitamin E, were incubated with CuCl2 (0-2400 microM) for 150 min. Dose and time-dependent decreases in hepatocyte viability (determined by trypan blue exclusion and lactate dehydrogenase release) due to copper toxicity correlated with production of malonyldialdehyde in E- and E+ hepatocytes. However, malonyldialdehyde generation did not accompany copper toxicity in E++ cells. Copper toxicity was enhanced in E- compared to E+ and E++ hepatocytes as assessed by cell viability studies and ultrastructural plasma membrane bleb formation. In vitro vitamin E repletion of E- hepatocytes restored resistance to copper and decreased malonyldialdehyde production proportionately. Thus vitamin E deficiency appeared to increase the susceptibility of hepatocytes to copper toxicity. We conclude that lipid peroxidation may not be the mechanism by which copper is toxic to isolated hepatocytes but that the site of injury may be thiol-rich cellular proteins.
Sokol
R J
RJ
Department of Pediatrics, University of Colorado School of Medicine, Denver 80262.
Devereaux
M W
MW
Traber
M G
MG
Shikes
R H
RH
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003300:Copper / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015227:Lipid Peroxidation; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008854:Microscopy, Electron; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*; D014811:Vitamin E Deficiency / Q000378:metabolism*
D014810:Vitamin E; D008315:Malondialdehyde; D003300:Copper