Evaluation of the Protective Effect of Citral, Silymarin, and Thymoquinone on Methotrexate-Induced Lung Injury in Rats.

Objectives: Several studies have reported that methotrexate is an anti-cancer and immunosuppressive drug leading to lung injury. Therefore, the present study aimed to investigate the protective effects of silymarin, citral, and thymoquinone on methotrexate-induced pulmonary toxicity.

Methods: Forty-eight rats were divided into six groups, including healthy, Methotrexate, and drug carrier control groups and silymarin, citral, and thymoquinone treatment groups. At the end of the experiment, the studied rats were anesthetized and sacrificed by CO₂. Lung tissue samples were isolated to measure the antioxidant activity and histopathological evaluation.

Results: In the thymoquinone treatment group, the concentration of total antioxidant capacity and Malondialdehyde increased and decreased significantly, respectively, compared to the methotrexate group. The histopathological evaluation of the lung of the methotrexate group showed hemorrhage and congestion, the nodule-like accumulation of mononuclear inflammatory lymphocytes around the blood vessel, a small number of neutrophils around the blood vessel, and the inflammatory cells around the small vessels. However, no significant pathological alterations were observed in the treatment groups, especially the thymoquinone treatment group.

Conclusion: Thymoquinone has the greatest protective effect on methotrexate-induced lung injury, probably due to its antioxidant effect.