title: The administration of renoprotective agents extends warm ischemia in a rat model.
abstract: OBJECTIVE
  Extended warm ischemia time during partial nephrectomy leads to considerable renal injury. Using a rat model of renal ischemia, we examined the ability of a unique renoprotective cocktail to ameliorate warm ischemia-reperfusion injury and extend warm ischemia time.
  
  
  METHODS
  A warm renal ischemia model was developed using Sprague-Dawley rats, clamping the left renal artery for 40, 50, 60, and 70 minutes, followed by 48 hours of reperfusion. An improved renoprotective cocktail referred to as I-GPM (a mixture of specific renoprotective growth factors, porphyrins, and mitochondria-protecting amino acids) was administered -24 hours, 0 hours, and +24 hours after surgery. At 48 hours, both kidneys were harvested and examined with hematoxylin and eosin and periodic acid-Schiff stains for the analysis of renal tubular necrosis. Creatinine, protein, and gene expression levels were also analyzed to evaluate several ischemia-specific and antioxidant response markers.
  
  
  RESULTS
  I-GPM treated kidneys showed significant reversal of morphologic changes and a significant reduction in specific ischemic markers lipocalin-2, galectin-3, GRP-78, and HMGB1 compared with ischemic controls. These experiments also showed an upregulation of the stress response protein, heat shock protein (HSP)-70, as well as the phosphorylated active form of the transcription factor, heat shock factor (HSF)-1. In addition, quantitative RT-PCR analyses revealed a robust upregulation of several antioxidant pathway response genes in I-GPM treated animals.
  
  
  CONCLUSIONS
  By histopathologic and several molecular measures, our unique renoprotective cocktail mitigated ischemia-reperfusion injury. Our cocktail minimized oxidative stress in an ischemic kidney rat model while at the same time protecting the global parenchymal function during extended periods of ischemia.
authors.affiliation: Department of Urology, New York Medical College, New York, NY 10075, USA. jhcohen4@gmail.com
authors.forename: Jacob
authors.initials: J
authors.lastname: Cohen
authors.forename: Thambi
authors.initials: T
authors.lastname: Dorai
authors.forename: Cheng
authors.initials: C
authors.lastname: Ding
authors.forename: Ines
authors.initials: I
authors.lastname: Batinic-Haberle
authors.forename: Michael
authors.initials: M
authors.lastname: Grasso
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D015151:Immunoblotting; D007511:Ischemia / Q000188:drug therapy / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects* / Q000473:pathology; D007684:Kidney Tubules / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020011:Protective Agents / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D052096:Warm Ischemia
chemical_list: D015415:Biomarkers; D020011:Protective Agents; D003404:Creatinine