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

Abstract

IntroductionMethotrexate 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.AimIn this study, the efficacy of clarithromycin in protecting against pulmonary fibrosis was investigated in the rat model for methotrexate-induced pulmonary fibrosis.Material and methodsA 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.ResultsNormal 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).ConclusionsClarithromycin was shown to be effective in protecting against methotrexate-induced pulmonary fibrosis; further studies should be performed to determine the dosage and safety.

Lungs, methotrexate and psoriasis

“…It might thus be useful to routinely perform chest CT in all patients with psoriasis requiring systemic treatments. Whether clarithromycin has a role against possible MTX‐induced pulmonary fibrosis remains to be seen …”

Involvement of Neuroinflammation in the Pathogenesis of Monocrotaline-Induced Pulmonary Hypertension

“…It is conceivable that some ICV-administered minocycline diffuses to the peripheral circulation to influence lung vasculature. This view is supported by the observations that minocycline attenuates pulmonary fibrosis in mice 23 . However, we believe that this is a less likely possibility in our experimental paradigm as we used a significantly lower concentration of minocycline.…”

“…However, we believe that this is a less likely possibility in our experimental paradigm as we used a significantly lower concentration of minocycline. Furthermore, effective concentrations of systemic minocycline in pulmonary disorders such as pulmonary fibrosis were significantly higher 23 . In the present study, to ensure that the observed effects were due to ICV infusion of minocycline, we verified cannula placement by microscopic visualization of the tract.…”

Ameliorating Effect of Alpha-lipoic Acid on Methotrexate-induced Histological and Biochemical Changes in The Lung of Adult Albino Rat

“…Similar alterations in oxidative stress biomarkers have been found in hepatic tissue [46] , and the sera [12] of rats received the same dose of MTX used in the present study. Kalemci et al [47] found a significant diminution of pulmonary SOD activity in the rats of the MTX group.…”

“…In agreement with Arpag et al [26] , the infiltration of inflammatory cells together with predominance of type II pneumocytes resulted in remarkable thickening of the interalveolar septa which was morphometrically confirmed. According to Kalemci, Akpınar [47] the toxicity of MTX to the lung is mediated through activation of P38 mitogen-activated protein kinases (MAPK). Yang et al [50] suggested that P38-MAPK plays a central role in inflammatory processes and the production of inflammatory mediators.…”