title: Pioglitazone, a Peroxisome Proliferator-Activated Receptor x03B3; Agonist, Ameliorates Chronic Kidney Disease by Enhancing Antioxidative Capacity and Attenuating Angiogenesis in the Kidney of a 5/6 Nephrectomized Rat Model.
abstract: OBJECTIVE
  Pioglitazone is a type of peroxisome proliferator-activated receptor x03B3; agonist and is capable of alleviating renal ischemia-reperfusion injury.
  
  
  METHODS
  A5/6 nephrectomized rat model was established to induce renal impairments mimicking chronic kidney diseases (CKDs). The effect of pioglitazone on renal structure, function, antioxidative capacity, and angiogenesis in the nephrectomized rats was assessed. Moreover, the expression of HIF-1α, eNOS, VEGF, Flt-1 and Flk-1 was determined to reveal the possible pathways through which pioglitazone exerted its beneficial effect on CKDs.
  
  
  RESULTS
  Subtotal nephrectomy caused severe damages to rat renal tissues, and administration of pioglitazone dramatically restored the structure and function of the kidney, which was evidenced by Periodic acid- Schiff staining and the reduced levels of urinary proteins, blood urea nitrogen, and creatinine. Furthermore, pioglitazone decreased the level of malondialdehyde and increased the level of superoxide dismutase in the injured renal tissues, suggesting that the antioxidative capacity in the injured kidney was augmented by pioglitazone. Additionally, pioglitazone inhibited HIF-1α-dependent angiogenesis by down-regulating the expression of a panel of angiogenic factors.
  
  
  CONCLUSIONS
  The current study demonstrates that pioglitazone benefits renal failure through activation of the antioxidative system and inhibition of angiogenesis in the injured kidney. Our study provides preliminary evidences for the potential application of this agent in the treatment of CKDs.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.forename: Tianhua
authors.initials: T
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.forename: Jiangmin
authors.initials: J
authors.lastname: Feng
authors.forename: Jianfei
authors.initials: J
authors.lastname: Ma
authors.forename: Lining
authors.initials: L
authors.lastname: Wang
authors.forename: Changlong
authors.initials: C
authors.lastname: Lu
authors.forename: Danan
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D008315:Malondialdehyde / Q000032:analysis; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009392:Nephrectomy; D009569:Nitric Oxide / Q000032:analysis; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000209:etiology; D013482:Superoxide Dismutase / Q000032:analysis; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047495:PPAR gamma; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D008315:Malondialdehyde; D003404:Creatinine; D013482:Superoxide Dismutase; D000077205:Pioglitazone