Periodicum biologorum, Vol. 110 No. 1, 2008.
Short communication, Note
Effect of radioprotective and chemoprotective drug (WR-2721) on toxicity of acetaminophen in mice
Joško Aleksić
; Knin General Hospital, Knin, Croatia
Domagoj Vergles
; Dubrava University Hospital, Zagreb, Croatia
Filip Čulo
; School of Medicine, University of Zagreb, Zagreb, Croatia
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).
Materials and Methods: 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.
Keywords
Hrčak ID:
29288
URI
Publication date:
29.2.2008.
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