Cytotoxicity evaluation after coexposure to perchloroethylene and selected peroxidant drugs in rat hepatocytes.
There is evidence of hepatotoxic effects caused by Perchloroethylene (PCE), presumably due to reactive metabolic intermediates; lipid peroxidation is under study as a potential mechanism of toxicity. We aimed to verify if PCE levels comparable to those reached in the blood of exposed subjects can cause cell damage and lipid peroxidation. The association of PCE with lipid peroxidation inducing drugs (cyclosporine A, valproic acid and amiodarone) was also tested on rat isolated hepatocytes. AST and LDH release, MTT test and lipid peroxidation assay showed that PCE determines dose-dependent effects on rat isolated hepatocytes. The toxic potential resulting from our data would be valproic acid < cyclosporine A < amiodarone. While valproic acid and cyclosporine caused a mild toxicity, the effects of amiodarone were more severe; in particular, the association of PCE with amiodarone showed a clear additive effect. The role of lipid peroxidation in the liver toxicity exerted by the tested compounds was confirmed by our data, and resulted relevant after treatment of cells with amiodarone and PCE. Extrapolating these results to human, we can suggest that a subject professionally exposed to PCE, who chronically assumes a lipid peroxidation inducing drug like amiodarone, may be potentially exposed to a higher risk of liver toxicity.
Costa
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Dip. Medicina Sociale del Territorio, Sez. Medicina del Lavoro, Azienda Ospedaliera Universitaria "G. Martino", via C. Valeria, 1-98125 Messina, Italy. citsal@unime.it
Barbaro
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Catania
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Silvari
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Germanò
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D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D000638:Amiodarone / Q000633:toxicity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005544:Forecasting; D005562:Formazans / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D016273:Occupational Exposure / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013385:Succinate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D013750:Tetrachloroethylene / Q000633:toxicity*; D013778:Tetrazolium Salts / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D024505:Tocopherols / Q000494:pharmacology / Q000627:therapeutic use; D014635:Valproic Acid / Q000494:pharmacology
D005562:Formazans; D013778:Tetrazolium Salts; D017392:Thiobarbituric Acid Reactive Substances; C079782:MTT formazan; D014635:Valproic Acid; D016572:Cyclosporine; D007770:L-Lactate Dehydrogenase; D013385:Succinate Dehydrogenase; D000594:Amino Acid Oxidoreductases; C025745:aspartate dehydrogenase; D000638:Amiodarone; D024505:Tocopherols; D013750:Tetrachloroethylene