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Assessment of renal protection from fenoldopam in experimental model of renal ischemia and reperfusion in rats under inhalation anesthesia with isoflurane

Grant number: 14/16308-7
Support type:Regular Research Grants
Duration: September 01, 2015 - November 30, 2017
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Norma Sueli Pinheiro Módolo
Grantee:Norma Sueli Pinheiro Módolo
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Assoc. researchers:Marcela Marcondes Pinto Rodrigues ; Márjorie de Assis Golim

Abstract

Background and Objective: Renal ischemia/reperfusion injury is a major cause of acute renal failure is a common phenomenon in the perioperative period and in critically ill patients hospitalized in intensive care units. The restoration of blood flow may aggravate the injury by the mechanism of ischemia and reperfusion (I/R). The goals of this study are: to evaluate possible renal protection of pre-infusion of fenoldopam and clonidine in an experimental model of I/R in rats anesthetized with isoflurane; monitor renal function of rats using early biomarkers (NGAL, IL-18, KIM-1 and L-FABP) correlating them with the RIFLE criteria that is determined by dosages of creatinine serum level; and define the presence of inflammatory cytokines (MAPKS) in renal tissue by immunohistochemistry using markers JNK, p38 and ERK.Method: 40 Wistar rats will be selected and allocated into four random groups: Ischemia Group (right nephrectomy, infusion of saline and maneuvers I / R , n = 10 ); Fenoldopam Group (right nephrectomy, infusion of fenoldopam, 5¼g.kg -1.min, intravenous infusion one hour before the ischemic and maneuvering procedure I / R, N = 10); Sham Group (laparotomy and infusion of saline , n = 10) and Clonidine Group (right nephrectomy, oral clonidine, 150 ug / kg / day / 2 days and four hours before the procedure ischemic, n = 10). Animals will be anesthetized with isoflurane. During the experimental procedure, weight (W), heart rate (HR), systolic blood pressure (SBP), diastolic (DBP) and mean (MAP) , intraoperative temperature (T) will be evaluated in moments M0 (initial monitoring), M1 (initial time), M2 (after reperfusion), M3 (2 hours after the start of reperfusion), M4 (4 hours after the start of reperfusion), M5 (6 hours after the start of reperfusion), M6 (8 hours after the start of reperfusion) and M7 (24 hours after M1). Plasma dosages of NGAL, IL -18, KIM - 1, L- FABP and creatinine will be held in moments M1, M2, M3, M4, M5, M6 and M7. Animals will be placed in metabolic cages for urine collection between M3 and M7 and dosages of urinary NGAL, IL -18, KIM-1 and L- FABP. The kidneys will be histologically analyzed for determination of acute tubular necrosis and evaluation of necrosis, apoptosis by flow cytometry and immunohistochemistry (mitogen-activated protein kinases-MAPK) JNK, p38 and ERK. (AU)