Antioxidant treatment for impaired hypoxic ventilatory responses in experimental diabetes in the rat

Inflammation, tissue hypoxia, and impaired hypoxic ventilatory response (HVR) are the intricately entwined features of diabetes which perpetuate the disease and its sequelae. Hyperglycemia, notably, is an oxygen consuming process due to enhanced cellular metabolism. Oxidative stress underlies diabetic pathogenesis and also is a crucial modulator of the hypoxic chemoreflex. The present study seeks to determine if suppressed ventilation in diabetes could be improved by antioxidant treatment. The study was performed in streptozotocin-induced diabetes in awake rats. Two weeks into full-fledged diabetes, the rats were divided into mangiferin (potent natural antioxidant)-treated and untreated, with the observation continued for another two weeks. The HVR was investigated plethysmographically and compared with the pre-diabetic baseline in the same animal. Thiobarbituric acid reactive substances, superoxide dismutase, and tumor necrosis factor-α were assayed in the serum. We demonstrate that mangiferin reversed the suppressed HVR and acted toward normalization of oxidative and inflammatory stress. In conclusion, mangiferin holds a therapeutic promise in breaking the mesh of chronic tissue hypoxia, inflammation, and oxidative stress in diabetes by enhancing ventilation.