Ivermectin Attenuates Methotrexate-Induced Liver Fibrosis by Reducing TGF-β and Syndecan-1 Expression
<i>Background and Objectives:</i> Methotrexate (MTX) is widely used in clinical settings but is often associated with hepatotoxic side effects, including oxidative stress, inflammation, and fibrosis. Novel therapeutic strategies are needed to mitigate MTX-induced liver injury. This study...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
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| Series: | Medicina |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1648-9144/61/6/1036 |
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| Summary: | <i>Background and Objectives:</i> Methotrexate (MTX) is widely used in clinical settings but is often associated with hepatotoxic side effects, including oxidative stress, inflammation, and fibrosis. Novel therapeutic strategies are needed to mitigate MTX-induced liver injury. This study aimed to evaluate the hepatoprotective effects of ivermectin in a rat model of MTX-induced hepatotoxicity. <i>Materials and Methods:</i> Thirty male Wistar albino rats were randomly divided into three groups (n = 10 per group): control (saline only), MTX (single intraperitoneal dose of 20 mg/kg MTX), and MTX + ivermectin (20 mg/kg MTX + 0.5 mg/kg/day ivermectin for 10 days). At the end of the experiment, blood and liver tissues were collected for histopathological and biochemical evaluation, including ALT, malondialdehyde (MDA), TGF-β, and syndecan-1 levels. <i>Results:</i> MTX administration significantly increased plasma and hepatic MDA, TGF-β, syndecan-1, and ALT levels, alongside histological evidence of necrosis, fibrosis, and inflammatory infiltration (<i>p</i> < 0.001 vs. control). Ivermectin treatment significantly attenuated these alterations, with reductions in MDA (both plasma and liver), TGF-β, syndecan-1, and ALT levels (<i>p</i> < 0.05–0.001 vs. MTX). Histological scoring also revealed improved liver architecture and decreased necrosis, fibrosis, and leukocyte infiltration. <i>Conclusions:</i> Ivermectin demonstrates a strong hepatoprotective effect against MTX-induced liver injury, likely through antioxidant, anti-inflammatory, antifibrotic, and endothelial-protective mechanisms. These findings support the repurposing potential of ivermectin in mitigating drug-induced hepatic damage. |
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| ISSN: | 1010-660X 1648-9144 |