engleski

THE ROLE OF PROSTAGLANDIN I2 IN MODIFYING ACUTE HEPATOTOXICITY OF ACETAMIONPHEN IN MICE

Prostaglandins (PGs) are lipid compounds that mediate variety of physiological and pathological functions in almost all body tissues and organs. PGI2 (prostacyclin), which is synthesized by the vascular endothelium, is a potent vasodilator, inhibits the aggregation of platelets in vitro and has cytoprotective effect on gastrointestinal mucosa. The aim of this study was to determine whether PGI2 is playing a role in host defense to toxic effect of acetaminophen (APAP). This was investigated in mice which were intoxicated with single lethal or high sublethal dose of APAP. APAP was administered to mice by gastric lavage and PGI2 agonists or antagonists were given i.p. 30 minutes before or 2 hours after administration of APAP. The toxicity of APAP was determined by observing the survival of mice during 48 hours and by measuring the concentration of alanine-aminotransferase (ALT) in plasma 20-24 hours after APAP administration. Mice were given either pure PGI2 (PGI2 sodium salt), it's stable agonist (Iloprost) or inhibitor of IP-receptor (CAY-10441). The results have shown that PGI2 exhibits a strong hepatoprotective effect when it was given to mice either before or after APAP (both increase of survival of mice and decrease of serum ALT level were statistically significant). Iloprost shown a similar effect (although not statistically significant), and CAY-10441 increased toxic effect of APAP if given 2 hours after its administration. Presently, we are examining the possible mechanisms of protective action of PGI2, such are the effects on production of cAMP, synthesis of NO and platelet aggregation parameters.

prostacyclin; acetaminophen; liver; toxicity; mice

nije evidentirano