[Inhibition by diethyldithiocarbamate (DEDTC) of acute hepatotoxic effects induced by polyhalogenated hydrocarbons (PHHC)].
Hemoglobin-free perfused rat livers were treated with carbon tetrachloride, chloroform, trichloroethylene and halothane by equilibrium of the perfusion medium with the varorous PHHCs. The resulting swelling of liver tissue, the potassium loss and the decrease of the perfusion rates were reduced by DEDTC to a different degree: The decrease of swelling, potassium loss and of the microcirculatory alteration by DEDTC was dose dependent in the case of carbon tetrachloride and halothane, whereas the effects of chloroform and trichloroethylene were not markedly influenced. Glutathione was mostly ineffective when given in similar doses. Pretreatment of rats with phenobarbital for 3 days increased itself swelling, K+-loss and reduction of perfusion rates, when the livers were perfused in absence of PHHCs. The effects of PHHCs in livers from pretreated rats were seldom greater but often lower than additive ones. Chiefly the effects of halothane were not markedly influenced by treatment of rats with phenobarbital. Isolated parenchymal liver cells were exposed to gas mixtures of O2, CO2 and PHHCs under controled conditions. Changes of the shape and staining of the cells were used for additional information. In view of these latter effects chloroform appeared as the most toxic and halothane as a nontoxic agent. DEDTC inhibits all effects of PHHCs demonstrated in isolated hepatocytes.
D000818:Animals; D002252:Carbon Tetrachloride Poisoning; D056486:Chemical and Drug Induced Liver Injury; D002725:Chloroform; D004050:Ditiocarb / Q000627:therapeutic use*; D005978:Glutathione / Q000627:therapeutic use; D006221:Halothane / Q000037:antagonists & inhibitors*; D006846:Hydrocarbons, Halogenated / Q000037:antagonists & inhibitors*; D008107:Liver Diseases / Q000517:prevention & control; D008297:Male; D008833:Microcirculation; D010477:Perfusion; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D013859:Thiocarbamates / Q000627:therapeutic use*; D014241:Trichloroethylene
D006846:Hydrocarbons, Halogenated; D013859:Thiocarbamates; D014241:Trichloroethylene; D002725:Chloroform; D004050:Ditiocarb; D005978:Glutathione; D006221:Halothane; D010634:Phenobarbital
Hemmung hepatotoxischer Frühwirkungen polyhalogenierter Kohlenwasserstoffe (PHKW) durch Diäthyldithiocarbamate (Dithiocarb)