Carvedilol as a valuable hepatoprotective agent against methotrexate-induced damage chiefly due to its anti-oxidant inheritence

Abstract

Background: Methotrexate is used in several heterogenic inflammatory and malignant disorders but life-sustaining liver organ is inevitably predisposed to damage by it. Carvedilol demonstrates anti-oxidant characteristic. The objective of this study was to explore the probable hepatic benefit it might provide when used concomitantly with methotrexate in rats. Methods: It was a laboratory-based randomized control trial done with collaborated effort of Pharmacology and Pathology Department, Army Medical College Rawalpindi along with National Institute of Health Islamabad, from March to July 2018. A total of 18 Sprague Dawley rats were randomly divided into 3 groups with 6 rats each. Untreated Group-I served as standard. On 7^th and 14^th day, 20 mg/Kg intraperitoneal methotrexate injection was given to rats in Group-II, while Group-III received carvedilol (10 mg/Kg/day) per-orally throughout with methotrexate intervention in-between. Blood was drawn for evaluation of liver function tests after giving chloroform anaesthesia on 15^th day and later sacrificed for collection of liver samples for the assessment of histopathological changes and oxidative stress induction measured by glutathione and malondialdehyde levels. Results were analysed on SPSS-22 using independent t-test and one-way ANOVA for quantitative analysis and histological changes were interpreted via Chi-square test. Results: Methotrexate caused significant elevation of liver enzymes and histoarchitectural damage with concurrent glutathione depletion and malondialdehyde extension. Carvedilol brought significant fading of these detrimental changes. Conclusion: Carvedilol can cause attenuation of methotrexate-induced hepatotoxicity predominantly by its anti-oxidant quality thereby preserving the normal histoarchitecture as well as reducing deleterious alterations in liver enzymes, glutathione and malonaldehyde levels.