NYMC Faculty Publications
The Administration of Renoprotective Agents Extends Warm Ischemia in a Rat Model
Author Type(s)
Faculty
Journal Title
Journal of Endourology / Endourological Society
First Page
343
Last Page
348
Document Type
Article
Publication Date
3-1-2013
Department
Biochemistry and Molecular Biology
Abstract
BACKGROUND AND PURPOSE: 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.
MATERIALS AND 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.
Recommended Citation
Cohen, J., Dorai, T., Ding, C., Batinic-Haberle, I., & Grasso, M. (2013). The Administration of Renoprotective Agents Extends Warm Ischemia in a Rat Model. Journal of Endourology / Endourological Society, 27 (3), 343-348. Retrieved from https://touroscholar.touro.edu/nymc_fac_pubs/5872
