engleski

THE ROLE OF GLUCAGON IN ACUTE ACETAMINOPHEN INDUCED HEPATOTOXICITY

The role of nitric oxide (NO) in hepatotoxicity induced by xenobiotics is still controversial. It is generally accepted that small, basal amount of NO, produced by constitutive NO synthase (cNOS) has a beneficial effect. However there are evidences that excessive production of NO from inducible NO synthase (iNOS) could be detrimental. Harbrecht et all. had shown that glucagon specifically inhibits iNOS expression and activity induced by LPS in rats. Therefore, we decided to investigate the effect of glucagon on acetaminophen (APAP) hepatotoxicity. In each experiment mice were divided into two groups, one group received glucagon (0, 5 mg/kg i.p.) 15-30 min before APAP and the other group received saline before APAP. To asses APAP (150 mg/kg i.p.) toxicity ALT levels in plasma were determined 6 and 24 hours following acetaminophen administration, or survival of mice were followed during 48 hours following APAP (300 mg/kg i.p.) administration. To asses iNOS activity plasma levels of nitrite/nitrate (the end products of NO metabolism) were determined 6 and 24 hours following APAP, using colorimetric assay based on the Griess reaction following the conversion of nitrate to nitrite using nitralyzer II kit. Mice in glucagon group had better survival and lower ALT levels at 6 and 24 hours after APAP, they also had lower plasma levels of nitrite/nitrate 6 hours after APAP, but there were no difference 24 hours after APAP. Currently we are determing iNOS expression in liver tissues.

glucagon; NO; iNOS; acetaminophen; acute liver toxicity

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