Carvedilol Could Ameliorate Acetaminophen Overdose Hepatotoxicity. Endogenous H₂S Contributes Such Effect: A Comparative Biochemical Evaluation

Physiology department, Faculty of Medicine, Benha University, Egypt

^*Corresponding Author

Mona Maher Allam

Faculty of Medicine

Benha University

Egypt

Cell no. +00201005413002

Email: monamaher8011@yahoo.com

Abstract

This study was designed to evaluate the effect of acute overdose of acetaminophen exposure, and determine the curative effect of carvedilol and explore the role of endogenous H₂S. Four groups of rats (n=10): groups I: control group, group II: acetaminophen (APAP) hepatotoxictoxic group, group III: APAP hepatotoxictoxic + carvedilol (CVD) treated group and group IV: APAP hepatotoxictoxic + CVD + hydrogen sulfide (H₂S) blocker; dl-propargylglycine (PAG) treated group. Animals of groups II, III, IV were given a single overdose of APAP; (2 g/kg) by oral gavages. Groups III and IV received CVD (10 mg/kg/day) by oral gavages, treatment was started 1 hr before APAP administration for 14 days. Animals of group IV received intraperitoneal injection of PAG (45 μmol/kg/day) for 14 days before CVD administration. On the 15th day, blood samples were obtained for estimation of liver enzymes activity levels and animals were sacrificed. Liver was extracted for histological examination and estimation of antioxidant enzymes activity and malondialdhyde (MDA) levels in liver tissue homogenate. Serum liver enzymes activity and MDA levels were significantly higher with significantly lower antioxidant enzymes activity in group II than in groups I and III. Serum liver enzymes activity and MDA levels were significantly higher with reduced antioxidant enzymes activity in group IV than in group III. We concluded that acute acetaminophen exposure destroyed hepatic architecture and altered enzymes activity. Carvedilol has a curative effect through preserved activity of antioxidants. Endogenous H₂S significantly contributes to carvedilol mediated effect.

Keywords: Acetaminophen, Hepatotoxicity, Carvedilol, Hydrogen Sulphid, Antioxidant enzymes

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