Radioprotectors as Late Preventive Agents against Carbon Tetrachloride Induced Liver Necrosis: Protection by 2-(3-Aminopropylamino) Ethylphosphorothioic Acid (WR2721)

Abstract

Administration of the radioprotective agent 2-(3-aminopropylamino) ethylphosphorothioic acid (WR2721) at 3 or 6 hr after carbon tetrachloride (CCl 4) administration significantly prevented the liver necrosis produced by the hepatotoxin at 24 hr. It is well known that WR2721 does not exert or minimally exerts a protective activity by itself. The compound is activated through dephosphorylation to the free thiol WR1065, a process which is catalyzed by an alkaline phosphatase. We observed that this enzyme was widely distributed in the rat body. The WR2721 pretreatment 30 min before CCl 4 administration modified the CCl 4 levels reaching the liver at 1 hr of poisoning and exerted a significant increase in the covalent binding (CB) of 14CCl 4-reactive metabolites to microsomal lipids at 3 hr. WR2721 did not modify the intensity of the CCl 4-induced lipid peroxidation (LP) process at 1 or 3 hr of poisoning. CCl 4--induced fat accumulation was not prevented when WR2721 was given 6 hr after CCl 4. In fact, protection might be due to a favorable modulation of late events occurring after CB or LP, events that remain to be elucidated.