Potentiation of chlorinated hydrocarbon toxicity by 2,5-hexanedione in primary cultures of adult rat hepatocytes.
Primary cultures of adult rat hepatocytes were used to investigate potentiation of halocarbon-induced hepatotoxicity by aliphatic ketones. Male Sprague-Dawley rats were pretreated with corn oil or 2,5-hexanedione (HD; 15 mmol/kg, po) in corn oil. Eighteen hours later the hepatocytes were isolated and cultured in Williams' Medium E and exposed to several concentrations of the hepatotoxicants carbon tetrachloride, chloroform, deutero-chloroform, or 1,1,2-trichloroethane. The cytotoxicity of these halocarbons as measured by release of the cytosolic enzyme lactate dehydrogenase into the culture medium was both time- and concentration-dependent. Halocarbon-induced cytotoxicity was exacerbated in cells isolated from HD-pretreated rats with significant increases in LDH release over cells isolated from corn oil-pretreated rats. In addition, chloroform was significantly more toxic than deutero-chloroform in hepatocytes from either corn oil- or HD-pretreated rats. Primary monolayer cultures were useful for studying ketone-induced potentiation, halocarbon-induced hepatocellular toxicity, and the mechanisms by which these effects occur.
D000818:Animals; D002478:Cells, Cultured; D003903:Deuterium; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006588:Hexanones / Q000633:toxicity*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D007659:Ketones / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D006588:Hexanones; D006843:Hydrocarbons, Chlorinated; D007659:Ketones; D003903:Deuterium; C011269:2,5-hexanedione; D007770:L-Lactate Dehydrogenase