A Pharmacodynamic Evaluation of the Protective Effects of Roxadustat Against Hypoxic Injury at High Altitude

Abstract Objectives: To explore the protective effects of roxadustat on hypoxia damage in the fast access to high altitude. Methods: BALB/C mice were randomly divided into control, roxadustat-7.8 mg/kg, roxadustat-15.6 mg/kg and roxadustat-31.2 mg/kg groups. The anti-hypoxic effectiveness of roxadustat in an optimal dose was evaluated by atmospheric pressure closed hypoxic experiment. Wistar rats were randomly divided into normal pressure, hypoxia model, acetazolamide and roxadustat groups to evaluate the protective effects against hypoxic damage. Animal blood was collected for arterial blood-gas analysis, cytokines detection, oxidative stress indicators, and their organs were harvested for pathological examination. Results: Compared with the control group, the survival time of mice were significantly prolonged in all groups. The time prolongation rate of the medium dose was 19.05%, which was the best dose. Compared with the hypoxia model group, the blood SatO2 and PaO2 in the roxadustat group were significantly increased; Erythrocyte content, hemoglobin content and hematocrit were significantly increased; Plasma levels of IL-6, TNF-α and IFN-γ were significantly decreased; MDA content in the myocardial, brain, lung and liver tissue were significantly decreased, SOD activity and GSH content in the tissue were significantly increased. The results of HE staining indicated that roxadustat could significantly improve the damage of heart, brain, lung, liver and kidney tissue after hypoxia in rats. Conlusions: Roxadustat can significantly prevent hypoxia-induced tissue damage, oxidative stress and inflammatory response indicating that roxadustat can obviously improve the adaptation to high-altitude exposure.