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

Abstract

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.