Mitigation of hypobaric hypoxia induced renal inflammatory alterations by quercetin prophylaxis

Abstract

The objective of the present study is to decipher the role of NF-κB and its associated downstream genes involved in causing inflammation in kidneys of rats under acute hypobaric hypoxia exposure. The study also aims at finding out the efficacy of quercetin in comparison with dexamethasone in prevention of hypobaric hypoxia induced renal inflammation. Sprague Dawley (SD) rats (n = 6) were preconditioned with 50 mg/Kg BW of quercetin, 1 h prior to hypobaric hypoxia exposure (12 h). The results revealed a significant increase in reactive oxygen species (ROS) generation and malondialdehyde (MDA) (p < 0.001) levels along with down regulation of GPx and SOD levels in kidney tissue of hypobaric hypoxia exposed rats as compared to control. However, ROS production and MDA levels in kidney tissues were reduced significantly (p < 0.001) with enhanced antioxidant enzyme levels (GPx and SOD) in rats fed with quercetin as compared to hypobaric hypoxia exposed control (p < 0.001). Protein expression analysis through western blotting and EMSA performed in nuclear extracts of kidneys, exhibited a significant upregulation of NF-κB under hypobaric hypoxic stress as compared to control. Whereas pretreatment with quercetin aids in downregulation of NF-κB expression in kidneys of rats as compared to the hypobaric hypoxia exposed group. Further, quercetin prophylaxis significantly reduced the expression of pro-inflammatory cytokines (TNF-α, IL-2 and IL-6), increased the anti-inflammatory cytokines (IL-10, IL-4 and TGF-β) along with reduced expression of cell adhesion molecules (ICAM-1, VCAM-1, E-selectin and P-selectin) in kidneys of rats under hypobaric hypoxia as compared to hypobaric hypoxia control. However, pre-treatment with dexamethasone was not as effective as quercetin, in controlling the renal inflammation. Furthermore, improved hematological parameters such as WBC, RBC, and platelet count indicated that quercetin is a well-functioning effective molecule under hypobaric hypoxic exposure. The histopathological and TEM findings, manifested the structural changes in tubular arrangements in kidneys of rats, and these changes were found to be modified by quercetin prophylaxis under hypobaric hypoxic stress. Hence, the present study indicates that, quercetin can be considered as a potential phytochemical flavonoid moiety in preventing the acute renal inflammation under hypobaric hypoxia.