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Published on: October 28, 2022
Silibinin attenuates methotrexate-induced pulmonary injury by targeting oxidative stress
Serdar Kalemci1, Yasar Topal2, Serkan Yasar Celik3
1Department of Chest Disease, Medical Faculty, Mugla Sıtkı Kocman University, Mugla 48000, Turkey.
Abstract:
The aim of the present study was to assess the protective effect of silibinin against methotrexate (MTX)-induced pulmonary toxicity. Rats were divided into four groups (MTX, MTX + silibinin, silibinin and control. MTX was injected intraperitoneally (i.p) into female Wistar rats (10 mg/kg/day for 3 days), which resulted in significant increases in the serum levels of alanine aminotransferase, aspartate aminotransferase and oxidant enzymes, including nitric oxide and myeloperoxidase. Furthermore, significant reductions were detected in the serum activity levels of the antioxidative enzymes, glutathione peroxidase and superoxide dismutase, when compared with the control group. However, administration of silibinin (100 mg/kg/day for 10 days, i.p.) was shown to ameliorate the MTX-induced pulmonary toxicity, as indicated by the normalization of the oxidative stress parameters. Furthermore, silibinin treatment was demonstrated to reduce the histopathological changes associated with MTX. In conclusion, silibinin exhibited protective effects against MTX-induced pulmonary toxicity, which may be attributed to its antioxidant activity.
Insights
Silibinin protects against lung damage caused by methotrexate (MTX). This study shows silibinin
Area of Science:
- Pharmacology and Toxicology
- Pulmonary Medicine
- Natural Product Chemistry
Background:
- Methotrexate (MTX) is a chemotherapy agent with known pulmonary toxicity.
- Oxidative stress plays a key role in MTX-induced lung injury.
- Silibinin, a flavonoid from milk thistle, possesses antioxidant properties.
Purpose of the Study:
- To evaluate the protective potential of silibinin against MTX-induced pulmonary toxicity in a rat model.
- To investigate the underlying mechanisms, focusing on oxidative stress markers.
Main Methods:
- Female Wistar rats were administered MTX (10 mg/kg/day for 3 days) to induce pulmonary toxicity.
- Groups received either MTX alone, MTX plus silibinin (100 mg/kg/day for 10 days), silibinin alone, or served as controls.
- Serum levels of liver enzymes (ALT, AST), oxidant enzymes (NO, MPO), and antioxidant enzymes (GPx, SOD) were measured.
Main Results:
- MTX administration significantly increased liver enzymes and oxidant markers while decreasing antioxidant enzyme activity.
- Silibinin treatment significantly ameliorated MTX-induced pulmonary toxicity, normalizing oxidative stress parameters.
- Histopathological examination revealed reduced MTX-induced lung damage following silibinin administration.
Conclusions:
- Silibinin demonstrates significant protective effects against methotrexate-induced pulmonary toxicity.
- The antioxidant activity of silibinin is likely responsible for its protective mechanism.
- Silibinin may be a potential therapeutic agent for mitigating MTX-related lung damage.
