Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Protective effect of erdosteine against methotrexate-induced hepatotoxicity in rats

Osama Abdelaziz Hassan¹, Entesar Farghally Amin², Rabab Ahmed Moussa³

¹Forensic Medicine and Clinical Toxicology Department; ²Pharmacology Department; ³Pathology Department, Faculty of Medicine, Minia University, 61111, Minia, Egypt.

For correspondence:- Rabab Moussa Email: rababmossa00@gmail.com Tel:+201004740750

Accepted: 23 June 2020 Published: 31 July 2020

Citation: Hassan OA, Amin EF, Moussa RA. Protective effect of erdosteine against methotrexate-induced hepatotoxicity in rats. Trop J Pharm Res 2020; 19(7):1465-1471 doi: 10.4314/tjpr.v19i7.19

© 2020 The authors.
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Abstract

Purpose: To study the possible mitigating effect of erdosteine (ERD) against methotrexate (MTX)-induced liver toxicity.

Methods: Male albino Sprague-Dawley rats were randomly assigned to four groups of 8 rats each, viz, vehicle control, MTX (20 mg/kg i.p.), MTX (20 mg/kg i.p.) + ERD (300 mg/kg) and ERD (300 mg/kg) groups. Serum levels of alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined by enzymatic colorimetric commercial kits while Hepatic tissue content of malondialdehyde (MDA), reduced glutathione (GSH), SOD and catalase (CAT) were also evaluated. In addition, measurement of the inflammatory cytokine, TNF-α, as well as histopathological examination and histochemical assessment were carried out.

Results: The results indicate that, compared to the control group, MTX group showed a remarkable elevation in oxidative stress as indicated by significantly lower levels of SOD, CAT and reduced glutathione, and increased tissue malondialdehyde (p < 0.05). MTX group exhibited significantly higher blood activities of ALT, AST and TNF-α, reflective of hepatocyte damage and inflammation (p < 0.05). In MTX group, significant hepatic degenerative changes were detected on histological examination, while marked apoptotic alternations were observed following immunohistochemical analysis of caspase-3 expression, when compared to control group. However, administration of ERD to rats ameliorated the changes in these parameters (p < 0.05).

Conclusion: Treatment with ERD in rats produced alleviation in hepatic oxidative stress, apoptosis, inflammation, and histological damage, when compared to MTX group. This study is the first to demonstrate the potentially protective effect of ERD-pretreatment against hepatotoxicity associated with MTX.

Keywords: Erdosteine, Methotrexate, Hepatotoxicity, Oxidant, Anti-oxidant