Protective effects of empagliflozin on methotrexate induced hepatotoxicity in rats.

Autor: Kalantari E; Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran., Zolbanin NM; Experimental and Applied Pharmaceutical Research Center, Urmia University of Medical Sciences, Urmia, Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran., Ghasemnejad-Berenji M; Experimental and Applied Pharmaceutical Research Center, Urmia University of Medical Sciences, Urmia, Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran. Electronic address: morteza.ghasemnejad@yahoo.com.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Jan; Vol. 170, pp. 115953. Date of Electronic Publication: 2023 Dec 07.
DOI: 10.1016/j.biopha.2023.115953
Abstrakt: Methotrexate (MTX), a folic acid antagonist, is commonly prescribed as a cytotoxic drug to treat several conditions such as leukemia and inflammation-related diseases, including rheumatoid arthritis and psoriasis. However, its use in clinical practice has been limited due to its fatal side effects, especially hepatotoxicity. Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that has recently been reported to exhibit anti-inflammatory and anti-oxidative properties. This study was aimed to evaluate the effect of Empagliflozin on liver injury induced by MTX in rats. The rats were divided into five groups as control, MTX (20 mg/kg; i.p.), Empagliflozin (30 mg/kg/day; i.p.), MTX and Empagliflozin (10 and 30 mg/kg/day; i.p.). Histopathologic alterations were examined for assessment of the liver injury. Furthermore, the levels of tissue malondialdehyde (MDA) and activity of anti-oxidative enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase, as well as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were evaluated. Our results revealed that treatment with Empagliflozin significantly improved histopathologic alterations, and elevated levels of AST and ALT induced by MTX administration. Additionally, altered activities of SOD, GPx, and catalase were significantly improved followed by Empagliflozin treatment. However, the higher dose of Empagliflozin was observed to have several benefits compared to the lower dose. Our data suggest that Empagliflozin might possess a protective role against MTX-induced hepatotoxicity by inhibiting oxidative stress in liver tissue.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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