Effect of radioprotective and chemoprotective drug (WR-2721) on toxicity of acetaminophen in mice

Background and Purpose: It is known, that WR-2721 WR-2721 - [S-2-(3-aminopropylamino)ethylposphorothioate] has radioprotective and chemoprotective effects on non-tumor tissues, and is now introduced into clinical tumor therapy protocols. We investigated whether WR-2721 have a protective role in acute liver injury induced with acetaminophen (APAP). Materials and Methods: CBA/H Zgr inbred mice of both sexes aged 12-16 weeds, weighing 20-25 g were used. Mice were given phenobarbitone-sodium in drinking water during 7 days (300 mg/kg) in order to induce hepatic drug-metabolizing enzymes., Thereafter; mice were fasted overnight and WR-2721 was given i.p. (50, 100 or 200 mg/kg). After 15-30 minutes they received acetaminophen (APAP; Paracetamol) 200 mg/kg by gastric tube. Animals were allowed food 4 hours late): The mortality of mice was followed for 3 days and serum aminotransferase levels were determined 24 hours after APAP administration. Results: Survival of mice was prolonged after all doses of WR-2721, but significantly only after the dose of 100 mg/g of WR-2721. Similarly, the pretreatment of mice with 100 mg/kg of WR-2721 highly significantly reduced serum aspartate aminotransferase levels (AST p < 0. 0005) and serum alanine aminotransferase levels (ALT p < 0.005). The doses of 50 and 200 mg/kg of WR-2721 also reduced AST and ALT but not significantly. Conclusions: These data showed that WR-2721 has definitive hepatoprotective effect which is significant in very restricted dose range.