Comparison of preventive and therapeutic effects of continuous exercise on acute lung injury induced with methotrexate

Abstract

Methotrexate (Mtx) is used to treat various diseases, including cancer, arthritis and other rheumatic diseases. However, it induces oxidative stress and pulmonary inflammation by stimulating production of reactive oxygen species and cytokines. Considering the positive effects of physical activity, our goal was to investigate the preventive and therapeutic role of continuous training (CT) on Mtx‐induced lung injury in rats. The rats were divided into five groups of 14 animals: a control group (C); a continuous exercise training group (CT; healthy rats that experienced CT); an acute lung injury with Mtx group (ALI); a pretreatment group with CT (the rats experienced CT before ALI induction), and a post‐treatment group with CT (the rats experienced CT after ALI induction). One dose of 20 mg/kg Mtx intraperitoneal was administered in the Mtx and training groups. Forty‐eight hours after the last exercise session all rats were sacrificed. According to our results, the levels of tumour necrosis factor‐α (TNF‐α), malondialdehyde (MDA), myeloperoxidase (MPO), GATA binding protein 3 (GATA3) and caspase‐3 in the ALI group significantly increased compared to the control group, and the levels of superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC), interleukin‐10 (IL‐10), forkhead box protein 3 (FOXP3), and T‐bet decreased. In contrast, compared to the acute lung injury group, pretreatment and treatment with CT reduced TNF‐α, MDA, MPO, GATA3 and caspase‐3 and increased SOD, GPX, TAC, IL‐10, FOXP3 and T‐bet levels. The effects of CT pretreatment were more significant than the effects of CT post‐treatment. Continuous exercise training effectively reduced oxidative stress and inflammatory cytokines and ameliorated Mtx‐induced injury, and the effects of CT pretreatment were more significant than the effects of CT post‐treatment.