Physiological and oxidative stress responses to intermittent hypoxia training in Sprague Dawley rats

Rapid ascent to high altitude and inability to acclimatize lead to high-altitude illnesses. Intermittent hypoxia (IH) conditioning has been hypothesized as a non-pharmacological strategy aiming to improve adaptive responses during high altitude ascent. In the recent years, IH training (IHT) has become increasingly popular among recreational and professional athletes owing to its ability to mitigate high altitude related problems. This study aimed at exploring the role of IHT in altitude acclimatization.

Male Sprague Dawley rats were subjected to IHT for 4 h consecutively for 5 days at 12% FiO₂ under normobaric conditions. To assess the effect of IHT in hypoxic acclimatization, animals were further exposed to extreme hypoxia (EH) at 8% FiO₂. Oxygen saturation (SpO₂), respiratory rate and heart rate were recorded during the exposure. Oxidative stress (ROS, MDA, and 4-HNE) and histopathological examinations were studied in the lung tissue sections. Hypoxia biomarkers, HIF-1α, EPO, VEGF, and BPGM were evaluated through western blotting in the lung tissue.

Assessment of the IHT showed that SpO₂ levels were found to be higher in the IH trained rats with a statistical difference of p < 0.01 in the first hour of hypoxia exposure as compared to the untrained rats. There was a significantly higher (p < 0.001) generation of ROS and MDA in the untrained rats as compared to the trained rats. Lipid peroxidation markers and systemic inflammatory marker were found to be expressed at much higher level in the untrained rats. There was a higher expression of HIF-1α (1.24-fold ↑), VEGF (1.14-fold ↑) and decrease in EPO (1.43-fold ↓) in the untrained rats as compared to trained rats.

Preconditioning with IHT resulted in the reduction in hypoxia induced oxidative stress during extreme hypoxia exposure and thus, maintaining redox balance as well as adjustment in the physiological changes in rats.