Ebselen ameliorates renal ischemia-reperfusion injury via enhancing autophagy in rats

Mol Cell Biochem. 2022 Jun;477(6):1873-1885. doi: 10.1007/s11010-022-04413-4. Epub 2022 Mar 26.

Abstract

Renal ischemia-reperfusion (I/R) injury is one of the most common causes of chronic kidney disease (CKD). It brings unfavorable outcomes to the patients and leads to a considerable socioeconomic burden. The study of renal I/R injury is still one of the hot topics in the medical field. Ebselen is an organic selenide that attenuates I/R injury in various organs. However, its effect and related mechanism underlying renal I/R injury remains unclear. In this study, we established a rat model of renal I/R injury to study the preventive effect of ebselen on renal I/R injury and further explore the potential mechanism of its action. We found that ebselen pretreatment reduced renal dysfunction and tissue damage caused by renal I/R. In addition, ebselen enhanced autophagy and inhibited oxidative stress. Additionally, ebselen pretreatment activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. The protective effect of ebselen was suppressed by autophagy inhibitor wortmannin. In conclusion, ebselen could ameliorate renal I/R injury, probably by enhancing autophagy, activating the Nrf2 signaling pathway, and reducing oxidative stress.

Keywords: Autophagy; Ebselen; Nrf2-signaling pathway; Oxidative stress; Renal ischemia–reperfusion injury.

MeSH terms

  • Animals
  • Autophagy
  • Humans
  • Isoindoles / pharmacology
  • NF-E2-Related Factor 2* / metabolism
  • Organoselenium Compounds
  • Oxidative Stress
  • Rats
  • Reperfusion Injury* / metabolism

Substances

  • Isoindoles
  • NF-E2-Related Factor 2
  • Organoselenium Compounds
  • ebselen