title: Inhibition of glycogen synthase kinase-3β attenuates acute kidney injury in sodium taurocholate‑induced severe acute pancreatitis in rats.
abstract: The aim of the present study was to investigate the efficacy of 4‑benzyl‑2‑methyl‑1,2,4‑thiadiazolidine‑3,5‑dione (TDZD‑8), the selective inhibitor of glycogen synthase kinase‑3β (GSK‑3β), on the development of acute kidney injury in an experimental model of sodium taurocholate‑induced severe acute pancreatitis (SAP) in rats. The serum amylase, lipase, interleukin‑1β and interleukin‑6 levels, and the pancreatic pathological score were examined to determine the magnitude of pancreatitis injury. The serum creatinine and blood urea nitrogen levels, myeloperoxidase (MPO) activity and renal histological grading were measured to assess the magnitude of SAP‑induced acute kidney injury. The activation of nuclear factor‑κB (NF‑κB) was examined using an immunohistochemistry assay. The expression of GSK‑3β, phospho‑GSK‑3β (Ser9), tumour necrosis factor‑α (TNF‑α), intercellular adhesion molecule‑1 (ICAM‑1) and inducible nitric oxide synthase (iNOS) protein in the kidney was characterised using western blot analysis. TDZD‑8 attenuated (i) serum amylase, lipase and renal dysfunction; (ii) the serum concentrations of proinflammatory cytokines; (iii) pancreatic and renal pathological injury; (iv) renal MPO activity and (v) NF‑κB activation and TNF‑α, ICAM‑1 and iNOS protein expression in the kidney. The results obtained in the present study suggest that the inhibition of GSK‑3β attenuates renal disorders associated with SAP through the inhibition of NF‑κB activation and the downregulation of the expression of proinflammatory cytokines, TNF‑α, ICAM‑1 and iNOS in rats. Blocking GSK‑3β protein kinase activity may be a novel approach to the treatment of this inﬂammatory condition.
authors.affiliation: Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Kailiang
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Wenhong
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Teng
authors.initials: T
authors.lastname: Zuo
authors.affiliation: Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary and Laparoscopic Surgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000378:metabolism*; D000681:Amylases / Q000097:blood; D000818:Animals; D001806:Blood Urea Nitrogen; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000378:metabolism; D008049:Lipase / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D013656:Taurocholic Acid; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D008049:Lipase; D000681:Amylases