engleski

The effect of radioprotective and chemoprotective drug (WR-2721) on toxicity of actaminophen in mice

Abstract 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 whetherWR-2721 have a protective role in acute liver injury induced with acetaminophen (APAP). Material and Method: CBA/H Zgr inbred mice of both sexes aged 12– 16 weeks, 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 andWR-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 later. 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 ofWR-2721, but significantly only after the dose of 100 mg/kg 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.

WR-2721; acetaminophen

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