ABSTRACT
BACKGROUND: Hyperglycemia is associated with a decreased tolerance to ischemia and an increased severity of renal ischemia reperfusion (I/R) injury. It has been suggested that erythropoietin (EPO) attenuates this effect in normoglycemic animals. This study sought to examine the effects of EPO on treatment renal I/R injury (IRI) in transiently hyperglycemic rats. MATERIAL AND METHODS: Twenty-eight male Wister rats anesthetized with isoflurane received glucose (2.5 g.kg(-1) intraperitoneally) before right nephrectomy. They were randomly assigned to four groups: sham operation (S); IRI (ISO); IRI+EPO, (600 UI kg(-1) low-dose EPO [EL]); and IRI+EPO 5000 UI kg(-1) (high-dose EPO [EH]). IRI was induced by a 25-minute period of left renal ischemia followed by reperfusion for 24 hours. Serum creatinine and glucose levels were measure at baseline (M1), immediately after the ischemic period (M2), and at 24 hours after reperfusion (M3). After sacrificing the animals, left kidney specimens were submitted for histological analysis including flow cytometry to estimate tubular necrosis and the percentages of apoptotic, dead or intact cells. RESULTS: Scr in the ISO group was significantly higher at M3 than among the other groups. Percentages of early apoptotic cells in ISO group were significantly higher than the other groups. Percentages of late apoptotic cells in S and ISO groups were significantly greater than EL and EH groups. However, no significant intergroup differences were observed regarding the incidence of tubular necrosis. CONCLUSIONS: Our results suggested that, although not preventing the occurrence of tubular necrosis, EPO attenuated apoptosis and glomerular functional impairment among transiently hyperglycemic rats undergoing an ischemia/reperfusion insult.
Subject(s)
Apoptosis/drug effects , Erythropoietin/pharmacology , Hyperglycemia/complications , Kidney/drug effects , Kidney/surgery , Nephrectomy/adverse effects , Reperfusion Injury/prevention & control , Animals , Blood Glucose/metabolism , Creatinine/blood , Cytoprotection , Disease Models, Animal , Epoetin Alfa , Flow Cytometry , Kidney/blood supply , Kidney/pathology , Kidney Glomerulus/drug effects , Kidney Glomerulus/pathology , Kidney Tubules/drug effects , Kidney Tubules/pathology , Male , Necrosis , Rats , Rats, Wistar , Recombinant Proteins/pharmacology , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Time FactorsABSTRACT
BACKGROUND: The purpose of this investigation was to examine the effect of isoflurane, remifentanil, and preconditioning in renal ischemia/reperfusion injury (IRI). METHODS: All 52 male Wistar rats were anesthetized with isoflurane, intubated and mechanically ventilated. The animals were randomly divided into: S group (sham; n = 11) that underwent only right nephrectomy; as well as the I group of right nephrectomy and ischemia for 45 minutes by clamping of left renal artery. (n = 11); the IP (n = 9), the R (n = 10), and the RP (n = 11) groups. In addition, the R and RP animals received remifentanil (2 microg.kg(-1).min(-1)) during the entire experiment. The IP and RP group underwent ischemic preconditioning (IPC = three cycles of 5 minutes). Serum creatinine values were determined before and after IRI, as well as 24 hours later. In addition to an Histological study, cells from the left kidney were evaluated for apoptosis by flow cytometry (FCM). RESULTS: The Creatinine value of 0.8 +/- 0.2 mg/dl in the S group was significantly lower at 24 hours than the I 3.9 +/- 1.5 mg/dl; IP 2.6 +/- 1.7 mg/dl; R 3.3 +/- 2.8 mg/dl; or RP 1.8 +/- 0.5 mg/dl groups. The RP group value was significantly lower than those of the I, IP, and R groups (p < 0.05). The S group showed less proximal tubular cell damage than the I, IP, R, and RP groups (p < 0.05). The percentages of apoptotic cells (FITC(+)/PI(-)) were: S group = 11.6 +/- 6.5; I = 16.7 +/- 7.3; IP = 37.0 +/- 28.4; R = 11.7 +/- 6.6, and RP = 8.8 +/- 1.5. The difference between the IP vs RP group was significant. Similar percentages of necrotic cells (FITC(+)/PI(+)) and intact cells (FITC(-)/PI(-)) were observed among the groups. CONCLUSIONS: Ischemic preconditioning showed no protective effect in the isoflurane group (IP) but when isoflurane was administered associated with remifentanil (RP), there was a beneficial effect on the kidney, as demonstrated by flow cytometry and serum creatinine values.