Epalrestat suppresses cadmium-induced cytotoxicity through Nrf2 in endothelial cells

• DOI: 10.3892/etm.2021.9824
• Publication Date: 2021-02-24T08:09:06Z
• Authors: Ryosuke Tatsunami; Keisuke Sato; Yu Murao; Kaori Yama; Yang Yu; Shun Ohno; Yoshiko Tampo
• Keywords: Metallothionein

Cadmium (Cd) is an industrial and environmental pollutant that targets the vascular endothelium. The system critically affected by Cd toxicity. Recent studies have indicated association between diseases, although mechanisms of implications in diseases are not clear. purpose present study was to determine whether epalrestat (EPS), which used for treatment diabetic neuropathy, protects against Cd-induced cytotoxicity bovine aortic endothelial cells (BAECs). In study, effects EPS at near-plasma concentration were examined on BAECs. suppressed pretreatment with EPS. Nuclear factor erythroid 2-related 2 (Nrf2) a key transcription serves role regulating expression glutamate cysteine ligase, rate-limiting enzyme glutathione (GSH) synthesis. previous demonstrated increase GSH levels BAECs Nrf2 pathway. increased exposed Cd. protective ability disappeared following small interfering RNA transfection. addition, intracellular Cd, transporter ZIP8 metallothionein. To best our knowledge, current demonstrated, first time, suppresses upregulation may be associated suppression From these findings, it proposed regulation GSH, metallothionein promising therapeutic approach prevent