Hypoxia-inducible factor-1α dependent pathways mediate the renoprotective role of acetazolamide against renal ischemia-reperfusion injury

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Yu AnXuejun Li

Abstract

Acute kidney injury (AKI) is a major complication of kidney transplantation, resulting in early graft dysfunction. Since diuretic acetazolamide (AZA) has been shown to improve contrast induced AKI, we hypothesized that AZA also protected against ischemia-reperfusion (I/R) caused AKI. An in vivo mouse renal I/R injury model and an in vitro H2O2 stimulated HK-2 cell injury model were utilized to examine the renoprotective effect of AZA. Renal injury and blood flow were measured. Nitric oxide synthase (eNOS)/Nitric oxide (NO), cell apoptosis and hypoxia-inducible factor-1α (HIF-1α) changes were analyzed. AZA reduced kidney injury scores and improved renal function by decreasing serum creatinine and BUN levels after I/R. Impaired renal blood flow was restored by increasing eNOS activities and NO production, as indicated by Laser Doppler imaging. TUNEL staining presented that AZA reduced apoptotic cells due to attenuated caspase activation and increased Bcl-2/Bax ratio. Furthermore, HIF-1α induction by AZA was demonstrated. AZA also enhanced in vitro NO production, reduced cell apoptosis and increased HIF-1α expression. Knockdown of HIF-1α by RNAi confirmed that AZA exerted its protective role depending on HIF-1α. AZA's effects were...Continue Reading

Citations

Nov 27, 2015·Journal of Enzyme Inhibition and Medicinal Chemistry·Lorenzo Di Cesare MannelliClaudiu T Supuran
Sep 22, 2018·European Journal of Heart Failure·Wilfried MullensMatthias Dupont
Sep 4, 2015·The Journal of Pharmacology and Experimental Therapeutics·Mohamed BejaouiJoan Rosselló-Catafau
Aug 29, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shih-Hung TsaiShing-Jong Lin
Sep 26, 2019·The New England Journal of Medicine·Roxana MehranSteven D Weisbord
Aug 2, 2017·Anesthesia and Analgesia·Xiaoyi YuanHolger K Eltzschig
May 11, 2019·European Journal of Heart Failure·Frederik H VerbruggeWilfried Mullens
Jan 24, 2018·Journal of Applied Physiology·Alejandro Ciocci PardoBernardo V Alvarez
Sep 26, 2019·The New England Journal of Medicine·Estelle C NijssenUNKNOWN AMACING Investigators

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