Efficacy of clarithromycin as a protective agent in the methotrexate-induced pulmonary fibrosis model

Introduction
Methotrexate is a cytotoxic agent used in leukemia, and several other cancer types and at lower doses in auto-inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis and psoriasis. Macrolide antibiotics are effective against gram-positive and Gram-negative bacteria. They have anti-inflammatory activities as well. Clarithromycin is a macrolide with anti-inflammatory activity through blockage of the p38 MAPK signal cascade, which is involved in methotrexate-induced pulmonary toxicity.

Aim
In this study, the efficacy of clarithromycin in protecting against pulmonary fibrosis was investigated in the rat model for methotrexate-induced pulmonary fibrosis.

Material and methods
A total of 30 female rats were divided into three groups. Group I was administered intraperitoneal and intragastric saline; group II was administered oral 3 mg/kg methotrexate; and group III was administered oral 3 mg/kg methotrexate + intraperitoneal 200 mg/kg clarithromycin for 28 days. Histopathological analyses of the lung tissues were performed under light microscopy.

Results
Normal histopathological changes were observed in the control group. Pulmonary fibrosis was significantly higher in the methotrexate group than in the other groups (p < 0.005).

Conclusions
Clarithromycin was shown to be effective in protecting against methotrexate-induced pulmonary fibrosis; further studies should be performed to determine the dosage and safety.