This study aimed to evaluate the protective effects of roxadustat against hypoxia-induced injury during rapid ascent to high altitude. BALB/C mice were randomly assigned to receive roxadustat at doses of 7.8, 15.6, or 31.2 mg/kg, or to control groups. The anti-hypoxic efficacy of roxadustat at the recommended dose was assessed using a controlled atmospheric pressure hypoxia model. Additionally, Wistar rats were randomly allocated to groups exposed to normal oxygen, hypoxia, acetazolamide, or roxadustat to assess protection against hypoxic injury. Blood samples were collected for arterial blood gas analysis, inflammatory markers, and oxidative stress measurements, while tissue samples were subjected to histopathological examination. Roxadustat treatment significantly prolonged survival time in mice compared with the normal oxygen group, with the medium dose producing the greatest increase (19.05%). In rats, roxadustat improved blood oxygen saturation (SatO2) and arterial oxygen partial pressure (PaO2), and significantly elevated erythrocyte count, hemoglobin, and hematocrit levels. Plasma concentrations of IL-6, TNF-α, and IFN-γ were markedly reduced. Roxadustat also attenuated oxidative stress in hypoxic tissues. Histological analysis revealed that roxadustat substantially mitigated hypoxia-induced damage in the heart, brain, lungs, liver, and kidneys. Roxadustat effectively alleviates hypoxia-induced inflammation, oxidative stress, and organ damage, demonstrating its potential to enhance physiological adaptation to high-altitude exposure.
