title: GSK-3beta Inhibitor Induces Expression of Nrf2/TrxR2 Signaling Pathway to Protect against Renal Ischemia/Reperfusion Injury in Diabetic Rats.
abstract: OBJECTIVE
  Diabetes mellitus (DM) can lead to renal damage and dysfunction, and exacerbate renal ischemia/reperfusion injury (RI/RI). The aim of this study was to investigate the protective effect of GSK-3β inhibitor TDZD-8 against RI/RI through Nrf2/TrxR2 signaling pathway in a rat DM model.
  
  
  METHODS
  A DM rat model was established by a single injection of streptozocin. Diabetic rats were pretreated with TDZD-8 (1 mg/kg bw) or TDZD-8+auranofin (10 nmol/L, 5ml/kg bw), and then subjected to 45-min ischemia and 24-h reperfusion. Rats were equally randomized into four groups: a Sham-operated group, a RI/RI group, a TDZD-8 group, and a TDZD-8+auranofin group. Serum levels of BUN and Scr were measured. SOD activity, MDA content, and Nrf2, TrxR2 and caspase-3 expressions in rat kidney tissues were determined.
  
  
  RESULTS
  Renal function was improved, oxidative stress and cell apoptosis were reduced, and the expression of Nrf2 and TrxR2 was up-regulated in TDZD-8 treated rats as compared with those in auranofin treated rats.
  
  
  CONCLUSIONS
  TDZD-8 may exert its protective effect against RI/RI by regulating the Nrf2/TrxR2 signaling pathway in the kidney tissue in DM.
authors.affiliation: Department of Pathology and Nephrology, Jiaxing Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Jiaxing, Zhejiang Province, P.R.China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Shen
authors.forename: Fei
authors.initials: F
authors.lastname: Tong
authors.forename: Guangtao
authors.initials: G
authors.lastname: Xu
authors.forename: Ruilin
authors.initials: R
authors.lastname: Shen
mesh_terms: D000818:Animals; D001310:Auranofin / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D000071679:Glycogen Synthase Kinase 3 beta / Q000037:antagonists & inhibitors*; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*; D013830:Thiadiazoles / Q000494:pharmacology*; D054482:Thioredoxin Reductase 2 / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C494356:4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D013830:Thiadiazoles; D001310:Auranofin; D054482:Thioredoxin Reductase 2; D000071679:Glycogen Synthase Kinase 3 beta