2-Methyl-piperazine-dithioformate, a new liver and radio-protector.

A series of d ithiopiperazine derivatives was studied for possible protective activity against agents inducing liver degeneration and the damage induced by x irradiation. The most active a gent tested was 2-methylpiperazine dithioformate (DTP). DTP injected intraperitoneally had an LD/sub 50/ of 740 mg/ kg in mice and 2000 mg/kg in rats by the oral route. It afforded rats protection against the liver injury induced by feeding a high-fat diet, pyridine, or ethionine. DTP was much more effective than cysteamine or methionine in preventing hepatic necrosis induced by a combined x i-rradiation and carbon tetrachloride treatment. However, in rats given a single whole-body 1000-r dose of x irradiation, DTP was slightly less effective than cystea-mine in prolonging survival (20 vs 32 days compared with 8 days in untreated control rats). It also partially blocked the fall in intestinal DNA content induced by irradiation or by nitrogen mustard treatment. (H.H.D.)