Carvedilol as a valuable hepatoprotective agent against methotrexate-induced damage chiefly due to its anti-oxidant inheritence
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 7th and 14th 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 15th 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.
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