Experimental Study of the Possible Hepatoprotective Effects of Some Agents Against Liver Damage Induced by Paracetamol orParaquat

Abstract

The present investigation aimed at questioning and examining the possible potential protective effects of some agents against paracetamol- or paraquat­ induced hepatotoxicity. Four main sets of experiments were performed. The first one was carried out to determine the doses of paracetamol or paraquat that produce suitable submaximal hepatotoxic effects. In this experiment, paracetamol was orally given to 18 h fasted rats at three dose levels, namely 0.5, 1 and 2 g!kg, whereas paraquat was intraperitoneally injected at doses of 35, 50 and 70 mg/kg. The hepatotoxic potential was evaluated based on effects on serum transaminases, liver adenosine triphosphate (ATP) content as well as histologic examination of liver tissues. According to the obtained results, the chosen dose of paracetamol was I g/kg while that of paraquat was 50 mg/kg. The second and third sets of experiments were conducted to evaluate the possible in vivo protective effect of the test drugs namely vitamin C (1 g!kg), silymarin (500 mg/kg), diosmin (400 mg/kg), selenium (50 J.Lg/kg) and zinc (30 mg!kg), given orally as single- or as repeated-dose (2 weeks) administration against paracetamol- or paraquat-induced hepatotoxicity. The hepatoprotective effects of the test drugs were evaluated regarding their effects on: 1- Liver function tests: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities as well as serum total and direct bilirubin levels. 2- Oxidative stress biomarkers: lactate dehydrogenase (LDH), thiobarbituric acid reactive substances (TBARS), protein thiols (Pr-SHs), reduced glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) levels or activities in blood and liver tissue. 3- Total protein, albumin, globulin and albumin/globulin levels in blood and liver 'tissue. 4- Energy content marker: ATP content in liver.