title: Exendin-4 ameliorates renal ischemia-reperfusion injury in the rat.
abstract: BACKGROUND
  Glucagon-like peptide-1 receptor (GLP-1R) activation exerts protective effects against reactive oxygen species by inducing the oxidative defense gene heme oxygenase-1 (HO-1), and provides protection in mice against transient focal cerebral ischemia and ischemia-reperfusion injury in the rat heart. GLP-1R is also expressed in the kidney, but it is unknown whether GLP-1R activation is able to protect against ischemia-reperfusion injury in the rat kidney.
  
  
  METHODS
  We used a rat model of renal ischemia-reperfusion injury. The rats were pretreated with the GLP-1R agonist, exendin-4 before reperfusion. We used real-time polymerase chain reaction to evaluate expression of the oxidative defense gene HO-1 and Western blot analysis for HO-1 and GLP-1R. Renal function was assessed at baseline and 24 and 72 h after reperfusion. The kidneys were processed for histologic and morphometric analysis, caspase-3, and ED1 immunohistochemistry at 72 h. The degree of apoptosis of the renal tubular cells was determined using terminal deoxynucleotidyl transferase deoxyuridine triphosphate-biotin nick end labeling assays.
  
  
  RESULTS
  Exendin-4 pretreatment resulted in GLP-1R activation and upregulation of HO-1. Preconditional activation of GLP-1R significantly improved the serum creatinine levels compared with vehicle (P < 0.05). Furthermore, tissue injury, caspase-3 and ED1 expression, and apoptosis were less severe, as quantified by application of a standardized histologic scoring system in a blinded manner.
  
  
  CONCLUSIONS
  These results have demonstrated that preconditional activation of the GLP-1R with exendin-4 in the kidney significantly protected against ischemia-reperfusion injury in rats by increasing HO-1 expression.
authors.affiliation: Department of Urologic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.forename: Heng
authors.initials: H
authors.lastname: Li
authors.forename: Zhendi
authors.initials: Z
authors.lastname: Wang
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Shi
authors.forename: Guosong
authors.initials: G
authors.lastname: Jiang
authors.forename: Fuqing
authors.initials: F
authors.lastname: Zeng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008264:Macrophages / Q000187:drug effects; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014688:Venoms / Q000494:pharmacology*
chemical_list: C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide; D003404:Creatinine; D051547:Heme Oxygenase-1
keywords: Apoptosis; Caspase-3; Exendin-4; Glucagon-like peptide-1; HO-1; Heme oxygenase-1; Macrophage; Male rats; Renal ischemia-reperfusion