title: Renoprotective potency of heme oxygenase-1 induction in rat renal ischemia-reperfusion.
abstract: OBJECTIVE
  Renal injury caused by ischemia-reperfusion (IR) can lead to acute renal failure or delayed graft function. Renal ischemia-reperfusion (RIR) induces inflammatory disorders via activation of arachidonic acid metabolism into prostaglandin E(2) (PGE(2)). Two inducible enzymes, COX-2 and microsomal prostaglandin E synthase (mPGES), regulate PGE(2) production. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme activated during cellular stress. Overexpression of HO-1 is beneficial in transplantation models including antigen-independent IR injury, acute and chronic allograft rejection.
  
  
  METHODS
  We investigated the effect of HO-1 induction on the COX pathway, antioxidant enzyme activities, malondialdehyde (MDA) levels, and apoptosis in rat kidneys subjected to 45 min ischemia and 1 h or 24 h reperfusion. Rats were injected intraperitoneally with either: 50 mg/kg hemin (HO-1 inducer groups: H1, H2); 50 micromol/kg ZnPP (HO-1 inhibitor groups: Hz1, Hz2); or 0.9% saline (control groups: r1, r2). Sham animals (Sh) did not undergo RIR.
  
  
  RESULTS
  Serum creatinine increased significantly after RIR (r vs Sh; p <0.05). Hemin treatment induced a significant decrease in serum creatinine after RIR (H vs r; p <0.05) whereas ZnPP treatment significantly increased serum creatinine levels (Sh vs Hz; p <0.05). Hemin reduced the severity of acute tubular necrosis and significantly reduced COX-2 and mPGES expression (p <0.05). Hemin did not alter depleted antioxidant enzyme activity but did decrease levels of MDA (p <0.05). Hemin also reduced caspase-3 expression.
  
  
  CONCLUSIONS
  HO-1 decreased the degree and severity of tubular damage after IR, probably by attenuating the cytotoxic effects of inflammatory infiltrates and apoptosis.
authors.affiliation: Laboratoire de Chirurgie Expérimentale, UPRES EA 1602, Université Paris-Sud 11, Faculté de Médecine, Le Kremlin Bicêtre, France. peschwege@yahoo.com
authors.forename: Mohammed Koussai
authors.initials: MK
authors.lastname: Chok
authors.forename: Sophie
authors.initials: S
authors.lastname: Ferlicot
authors.forename: Marc
authors.initials: M
authors.lastname: Conti
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Almolki
authors.forename: Antoine
authors.initials: A
authors.lastname: Dürrbach
authors.forename: Sylvain
authors.initials: S
authors.lastname: Loric
authors.forename: Gérard
authors.initials: G
authors.lastname: Benoît
authors.forename: Stéphane
authors.initials: S
authors.lastname: Droupy
authors.forename: Pascal
authors.initials: P
authors.lastname: Eschwège
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006427:Hemin / Q000008:administration & dosage; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D008297:Male; D008315:Malondialdehyde / Q000276:immunology / Q000378:metabolism*; D011524:Protoporphyrins / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
chemical_list: D011524:Protoporphyrins; C017803:zinc protoporphyrin; D008315:Malondialdehyde; D006427:Hemin; D003404:Creatinine; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; D053148:Caspase 3