Potentiation of carbon tetrachloride-induced lipid peroxidation by trichloroethylene in isolated rat hepatocytes: no role in enhanced toxicity.
Hepatocytes isolated from Sprague-Dawley rats were exposed to carbon tetrachloride together with various concentrations of trichloroethylene over a 40-fold range. A potentiation of carbon tetrachloride-induced lipid peroxidation by trichloroethylene and an enhanced toxicity on combined exposure were clearly demonstrated. Additionally, rats were treated 2.5 hr before isolation of hepatocytes, which were then exposed to carbon tetrachloride. Lipid peroxidation and potassium ion leakage were increased in these cells. Some incubations included the antioxidant N,N'-diphenyl-p-phenylenediamine (DPPD) while others contained dithiothreitol (DTT), a thiol reducing compound. DPPD inhibited lipid peroxidation while DTT did not. Neither, however, was able to inhibit the toxicity. Assays to estimate total and nonprotein bound sulfhydryl groups were also performed. There was no indication of a causative role for cellular sulfhydryl groups in the enhanced toxicity. Therefore, our data show that lipid peroxidation is not responsible for the trichloroethylene-induced enhancement of toxicity in hepatocytes due to carbon tetrachloride. Furthermore, there is no evidence to indicate a role for sulfhydryl groups in this response.
Kefalas
V
V
National Institute of Occupational Health and Safety, University of Sydney, New South Wales, Australia.
Stacey
N H
NH
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004229:Dithiothreitol / Q000494:pharmacology; D004357:Drug Synergism; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010655:Phenylenediamines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014241:Trichloroethylene / Q000633:toxicity*
D000975:Antioxidants; D010655:Phenylenediamines; D013438:Sulfhydryl Compounds; D014241:Trichloroethylene; D002251:Carbon Tetrachloride; C004845:N,N'-diphenyl-4-phenylenediamine; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D011188:Potassium; D004229:Dithiothreitol