title: The effects of PPAR-γ agonist pioglitazone on renal ischemia/reperfusion injury in rats.
abstract: BACKGROUND
  Acute renal failure due to renal ischemia/reperfusion (IR) injury is a significant clinical problem in cardiovascular surgery. Reactive oxygen species and inflammation play essential roles in the pathophysiology of IR injury. Matrix metalloproteinases (MMPs) are enzymes that play important roles in inflammation and mediate extracellular matrix degradation. It is known that peroxisome proliferator-activated receptor-γ agonists have antiinflammatory and antioxidant effects. In the present study, we aimed to investigate the effects of pioglitazone, a synthetic peroxisome proliferator-activated receptor-γ agonist, on MMPs and oxidative stress in a renal IR injury model in rats.
  
  
  METHODS
  Male Wistar albino rats were divided into three groups: control (n = 7), placebo (n = 7; saline/p.o.), and pioglitazone (n = 7; 5 mg/kg/day/p.o.). In the control group, a right nephrectomy was conducted without left renal IR injury. In the placebo and pioglitazone groups, pretreatments were started 3 d before operation. In both groups, left renal pedicles were clamped for 60 min and then reperfused for 60 min. Paraffinized renal sections were evaluated histopathologically. Furthermore, expressions of MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, superoxide dismutase 1 (SOD1), and p47-phox/p67-phox subunits of NADPH oxidase were determined by immunostaining and scoring.
  
  
  RESULTS
  In the placebo group, renal IR injury induced diffuse tubular necrosis and intense acute inflammation, but pioglitazone inhibited these effects. MMP-2, MMP-9, and TIMP-2 expression increased in the placebo group. However, while MMP-2 and -9 expression decreased, TIMP-2 expression did not change in the pioglitazone group. p47-phox/p67-phox expression increased in the placebo group, but SOD1 expression did not change. Pioglitazone diminished p47-phox/p67-phox expression, whereas it enhanced SOD1 expression.
  
  
  CONCLUSIONS
  Our results suggest that pioglitazone might be helpful to reduce renal IR injury because of its antiinflammatory and antioxidant effects.
authors.affiliation: Faculty of Pharmacy, Department of Pharmacology, Ege University, Izmir, Turkey.
authors.forename: Buket
authors.initials: B
authors.lastname: Reel
authors.forename: Mehmet
authors.initials: M
authors.lastname: Guzeloglu
authors.forename: Alper
authors.initials: A
authors.lastname: Bagriyanik
authors.forename: Soner
authors.initials: S
authors.lastname: Atmaca
authors.forename: Koray
authors.initials: K
authors.lastname: Aykut
authors.forename: Gokhan
authors.initials: G
authors.lastname: Albayrak
authors.forename: Eyup
authors.initials: E
authors.lastname: Hazan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D023421:Models, Animal; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D047495:PPAR gamma / Q000819:agonists*; D010750:Phosphoproteins / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D047495:PPAR gamma; D010750:Phosphoproteins; D045162:Thiazolidinediones; C079789:neutrophil cytosol factor 67K; D019716:Tissue Inhibitor of Metalloproteinase-2; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077205:Pioglitazone