The antihepatotoxic activity of dithiocarb as compared with six other thio compounds in mice

In mice, diethyldithiocarbamate (dithiocarb, 100 mg/kg i.p.) completely prevented the increments of serum enzyme activities (GOT, GPT, SDH) induced by oral administration of carbon tetrachloride (0.1 ml/kg), allyl alcohol (0.05 ml/kg), bromobenzene (0.25 ml/kg), and thioacetamide (50 mg/kg). In this respect, cysteine (200 mg/kg i.p.) was active against CCl₄ and bromobenzene, cysteamine (100 mg/kg i.p.) against CCl₄ and allyl alcohol, penicillamine (100 mg/kg i.p.) against allyl alcohol, thiazolidine carbonic acid (100 mg/kg i.p.) against bromobenzene, and thioctic acid (100 mg/kg i.p.) against allyl alcohol and thioacetamide. Dimercaprol (100 mg/kg i.p.) had a weak antidotal effect only against allyl alcohol poisoning. None of the tested antidotes inhibited serum enzyme elevations evoked by dimethyl nitrosamine (100 mg/kg p.o.). These findings prove the antihepatotoxic activity of diethyldithiocarbamate to be superior to that of all other thio compounds under observation.The lowest dose of dithiocarb active against carbon tetrachloride was 25 mg/kg i.p. The dose-response curves for serum-enzyme elevations induced by carbon tetrachloride (0.1–4 ml/kg p.o.) were shifted to the right under the influence of dithiocarb indicating a competitive antagonism. Dithiocarb (100 mg/kg i.p.) depressed the p-hydroxylation of aniline in the 9000 x g liver homogenate supernatant of mice by about 55%. Thus, the antihepatotoxic activity of dithiocarb seems to be the consequence of a decreased oxidase activity.