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Updated: Aug 6, 2026

Supramaximal Intensity Hypoxic Exercise and Vascular Function Assessment in Mice
Published on: March 15, 2019
High-intensity intermittent training ameliorates methotrexate-induced acute lung injury
Mohammad Amin Rajizadeh1,2,3, Mahdiyeh Haj Hosseini3,4, Mina Bahrami3,4
1Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran.
High-intensity intermittent training (HIIT) effectively combats lung damage caused by methotrexate by reducing inflammation and oxidative stress. This exercise intervention shows promise in protecting against and treating drug-induced lung injury.
Area of Science:
- Pulmonary Medicine
- Exercise Physiology
- Toxicology
Background:
- Methotrexate (MTX) is a widely used chemotherapeutic and immunosuppressive agent.
- MTX induces lung damage primarily through inflammation and oxidative stress.
- High-intensity intermittent training (HIIT) possesses known antioxidant and anti-inflammatory properties.
Purpose of the Study:
- To investigate the therapeutic efficacy of HIIT in mitigating MTX-induced lung injury in a rat model.
- To evaluate HIIT's effects on oxidative stress markers, inflammatory cytokines, and lung histopathology.
Main Methods:
- Seventy male Wistar rats were allocated into five groups: Control, HIIT, Acute Lung Injury (ALI), HIIT+ALI (pre-treatment), and ALI+HIIT (post-treatment).
- HIIT intervention was administered for 8 weeks.
- Assessed parameters included oxidative stress markers (MDA, TAC, SOD, GPx), inflammatory markers (MPO, TNF-α, IL-10), immune cell transcription factors (T-bet, GATA3, FOXP3), lung water content, capillary permeability, apoptosis (Caspase-3), and histopathology.
Main Results:
- MTX administration significantly increased pro-inflammatory and oxidative stress markers (TNF-α, MPO, GATA3, Caspase-3) and pulmonary edema.
- MTX treatment decreased antioxidant capacity and anti-inflammatory markers (TAC, SOD, GPx, IL-10, T-bet, FOXP3).
- HIIT (both pre-treatment and post-treatment) attenuated MTX-induced lung injury by reducing oxidative and inflammatory factors, edema, and improving histopathological outcomes, while enhancing antioxidant and anti-inflammatory markers.
Conclusions:
- HIIT demonstrates significant protective and therapeutic potential against methotrexate-induced lung injury in rats.
- The benefits of HIIT are attributed to its ability to counteract oxidative stress and inflammation.
- HIIT may serve as a valuable complementary therapy for patients experiencing MTX-related pulmonary toxicity.
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