Ivermectin Attenuates Methotrexate-Induced Liver Fibrosis by Reducing TGF-β and Syndecan-1 Expression

Area of Science:

• Hepatology
• Pharmacology
• Toxicology

Background:

• Methotrexate (MTX) is a widely used drug associated with significant hepatotoxicity.
• MTX-induced liver injury involves oxidative stress, inflammation, and fibrosis.
• There is a need for effective strategies to mitigate MTX-related liver damage.

Purpose of the Study:

• To investigate the hepatoprotective potential of ivermectin against MTX-induced liver injury.
• To evaluate the effects of ivermectin on biochemical and histopathological markers of liver damage in a rat model.

Main Methods:

• Thirty male Wistar albino rats were divided into control, MTX-only, and MTX + ivermectin groups.
• MTX was administered intraperitoneally, followed by oral ivermectin treatment.
• Liver tissues and plasma were analyzed for ALT, MDA, TGF-β, and syndecan-1 levels, along with histopathology.

Main Results:

• MTX significantly elevated plasma and liver MDA, TGF-β, syndecan-1, and ALT levels, causing necrosis, fibrosis, and inflammation.
• Ivermectin treatment significantly reduced these elevated markers and improved liver histology.
• Histological scoring showed decreased necrosis, fibrosis, and inflammatory cell infiltration in the ivermectin group.

Conclusions:

• Ivermectin exhibits significant hepatoprotective effects against MTX-induced liver injury.
• The protective mechanisms likely involve antioxidant, anti-inflammatory, antifibrotic, and endothelial protection.
• Ivermectin shows promise for repurposing to manage drug-induced hepatic damage.