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PLoS One. 2016 Jul 8;11(7):e0158810. doi: 10.1371/journal.pone.0158810. eCollection 2016.

Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury.

Author information

1
Department of Nephrology, Daejeon St. Mary Hospital, Daejeon, South Korea.
2
Department of Nephrology, Catholic University of Korea, Seoul, South Korea.
3
Clinical Research Institute, Daejeon St. Mary Hospital, Daejeon, South Korea.
4
Department of Nephrology, School of medicine, Chungnam National University, Daejeon, South Korea.
5
Department of Medical Science, School of medicine, Chungnam National University, Daejeon, South Korea.
6
Department of pathology, College of medicine, Yeonse University, Seoul, South Korea.

Abstract

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.

PMID:
27391020
PMCID:
PMC4938401
DOI:
10.1371/journal.pone.0158810
[Indexed for MEDLINE]
Free PMC Article

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