Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion InjuryReportar como inadecuado




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Dapagliflozin, a new type of drug used to treat diabetes mellitus DM, is a sodium-glucose cotransporter 2 SGLT2 inhibitor. Although some studies showed that SGLT2 inhibition attenuated reactive oxygen generation in diabetic kidney the role of SGLT2 inhibition is unknown. We evaluated whether SLT2 inhibition has renoprotective effects in ischemia-reperfusion IR models. We evaluated whether dapagliflozin reduces renal damage in IR mice model. In addition, hypoxic HK2 cells were treated with or without SGLT2 inhibitor to investigate cell survival, the apoptosis signal pathway, and the induction of hypoxia-inducible factor 1 HIF1 and associated proteins. Dapagliflozin improved renal function. Dapagliflozin reduced renal expression of Bax, renal tubule injury and TUNEL-positive cells and increased renal expression of HIF1 in IR-injured mice. HIF1 inhibition by albendazole negated the renoprotective effects of dapagliflozin treatment in IR-injured mice. In vitro, dapagliflozin increased the expression of HIF1, AMP-activated protein kinase AMPK, and ERK and increased cell survival of hypoxic HK2 cells in a dose-dependent manner. In conclusion, dapagliflozin attenuates renal IR injury. HIF1 induction by dapagliflozin may play a role in renoprotection against renal IR injury.



Autor: Yoon-Kyung Chang, Hyunsu Choi, Jin Young Jeong, Ki-Ryang Na, Kang Wook Lee, Beom Jin Lim , Dae Eun Choi

Fuente: http://plos.srce.hr/



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