Elucidating the potential role of quercetin in augmenting the acclimatization process via controlling high altitude induced redox imbalance in rats: A molecular approach

Hypoxia emerges as the major barrier at high altitude for military troops and mountaineers. Prophylaxis with carbonic anhydrase inhibitors like acetazolamide (ACZ) has been suggested for better adaptation and survival at altitude above 2500 m. The study present here compares the prophylactic efficacies of quercetin and acetazolamide in preventing Acute Mountain Sickness (AMS). We further aim to identify the potential pathway quercetin follows to exert its effects through binding studies with carbonic anhydrase (CA-II). Male SD rats (total number rats used=36) were supplemented orally with quercetin (50 mg/Kg BW) and acetazolamide (50 mg/Kg BW) and then subjected to hypobaric hypoxia (25,000 ft. for 12 h). Hypoxia induced oxidative imbalance, antioxidant inactivity and carbonic anhydrase activity were assessed in plasma of rats. The results obtained suggested that hypoxia induced oxidative imbalance (protein carbonylation) and antioxidant inactivity (glutathione reductase) was significantly restored by supplementation of quercetin in plasma of rats (p < 0.001). However, ACZ supplemented normoxia rats showed, enhanced levels of protein carbonylation in plasma of these rats in comparison with the normoxia control group. Prophylactic potential of both the drugs were further evaluated with hematological and blood gas parameters as well. Western blotting studies determined the differential expressions of EPO, Nrf-2 and HO-1 in rat kidney homogenates. Later, binding affinity of quercetin with CA-II was evaluated with Surface Plasmon Resonance (SPR). Quercetin considerably restored the expression of EPO, Nrf-2 and HO-1 to optimum levels by attenuating the oxidative stress and promoting the antioxidant milieu in the hypoxia exposed rats. SPR and molecular data does not support such inhibition of CA-II with quercetin. Thus, quercetin might have explored some other mechanism to attain the acclimatization in rats under hypoxia. These results indicate that, quercetin is a safe and potent drug for high altitude adjustments for better adaptability.