title: Protective effect of indomethacin in renal ischemia-reperfusion injury in mice.
abstract: OBJECTIVE
  To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs (NSAIDs) in renal ischemia-reperfusion injury (IRI) and the cyclooxygenase (COX)-1/2 blockade association by indomethacin (IMT) in the mice model.
  
  
  METHODS
  After the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses: 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine (SCr) using enzyme-linked immunosorbent assay (ELISA) kits. Kidney samples were analyzed by hematoxylin and eosin (H&E) and immunohistochemistry stainings.
  
  
  RESULTS
  The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage. The tumor necrosis factor α (TNF-α) activity in renal homogenates and interleukin 6 (IL-6) activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B2 to 6-keto-prostaglandin F1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups.
  
  
  CONCLUSIONS
  There was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.
authors.affiliation: Kidney Disease Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; Kidney Disease Center, Shaoxing Second Hospital, Shaoxing 312000, China.
authors.forename: Sheng-hong
authors.initials: SH
authors.lastname: Zhu
authors.forename: Li-jia
authors.initials: LJ
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Rong-jun
authors.initials: RJ
authors.lastname: Chen
authors.forename: Chuan
authors.initials: C
authors.lastname: Lin
authors.forename: Shi
authors.initials: S
authors.lastname: Feng
authors.forename: Juan
authors.initials: J
authors.lastname: Jin
authors.forename: Jiang-hua
authors.initials: JH
authors.lastname: Chen
authors.forename: Jian-yong
authors.initials: JY
authors.lastname: Wu
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000097:blood; D015237:Dinoprost / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007213:Indomethacin / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000293:injuries* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000517:prevention & control*; D013929:Thromboxane B2 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C078129:6-keto-prostaglandin F2alpha; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D015850:Interleukin-6; D008565:Membrane Proteins; D014409:Tumor Necrosis Factor-alpha; D013929:Thromboxane B2; D003404:Creatinine; D015237:Dinoprost; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse; D007213:Indomethacin
keywords: Dosage; Indomethacin (IMT); Ischemia-reperfusion injury (IRI); Non-steroidal anti-inflammatory drug (NSAID); Protective effect
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