Evaluation of renal protection from high doses of melatonin in an experimental model of renal ischemia and reperfusion in hyperglycemic rats.

BACKGROUND: Melatonin is a free radical scavenger with important actions in the study of renal ischemia and reperfusion (I/R). This study evaluated possible renal protection of high doses of melatonin in an experimental model of I/R in which rats were submitted to acute hyperglycemia under anesthesia with isoflurane. METHOD: Forty-four male Wistar rats, weighing more than 300 g, were randomly divided into 5 groups: G1, sham (n = 10); G2, melatonin (n = 10; 50 mg.kg(-1)); G3, hyperglycemia (n = 9; glucose 2.5 g.kg(-1)); G4, hyperglycemia/melatonin (n = 10; 2.5 g.kg(-1) glucose + melatonin 50 mg.kg(-1)); and G5, I/R (n = 5). In all groups, anesthesia was induced with 4% isoflurane and maintained with 1.5% to 2.0% isoflurane. Intraperitoneal injection of melatonin (G1, G4), glucose (G3, G4), or saline (G1, G5) was performed 40 minutes before left renal ischemia. Serum plasma values for creatinine and glucose were determined at baseline (M1), immediately following reperfusion (M2), and 24 hours after completion of the experiment (M3). Histological analysis was performed to evaluate tubular necrosis (0-5). RESULTS: Serum glucose was higher at M2 in the groups supplemented with glucose, hyperglycemia (356.00 ± 107.83), and hyperglycemia/melatonin (445.3 ± 148.32). Creatinine values were higher at T3 (P = .0001) for I/R (3.6 ± 0.37), hyperglycemia/melatonin (3.9 ± 0.46), and hyperglycemia (3.71 ± 0.69) and lower in the sham (0.79 ± 0.16) and melatonin (2.01 ± 1.01) groups, P < .05. Histology showed no necrosis injury in the G1, lesion grade 2 in the G2, and severe acute tubular necrosis in the G3: (grade 4), G4: (grade 5) and G5: (grade 4) groups (P < .0001). DISCUSSION: Melatonin protected the kidneys submitted to I/R in rats without hyperglycemia; however, this did not occur when the I/R lesion was associated with hyperglycemia. CONCLUSIONS: Due to its antioxidant and antiapoptotic action, melatonin was able to mitigate, but not prevent acute tubular necrosis in rats with hyperglycemia under anesthesia by isoflurane.

Caffeic acid phenethyl ester effects in the kidney during ischemia and reperfusion in rats anesthetized with isoflurane.

BACKGROUND: The purpose of this investigation was to examine the effect of caffeic acid phenethyl ester (CAPE) in renal ischemia/reperfusion injury in rats anesthetized with isoflurane (iso). METHODS: We randomly assigned 26 male Wistar rats anesthetized with isoflurane, intubated and mechanically ventilated to 3 groups: G1 (controls; n = 8), G2 (CAPE; n = 10), and G3 (ethanol; n = 8). Mean arterial pressure was monitored for anesthetic control. Intraperitoneal CAPE (G2) or ethanol (G3) injections were administered 40 minutes before left renal ischemia. All animals underwent right nephrectomy and the left kidney was submitted to ischemia for 25 minutes. Serum creatinine (cr) values were determined at the beginning (M1), end (M2), and 24 hours after the experiment (M3) upon intracardiac blood samples. The left kidney was removed for histologic analysis, using a scale for tubular necrosis (0-5, injury maximum). Statistical analysis was applied to serum creatinine and histological score injury considering statistical differences to be significant when P < .05. RESULTS: The cr values in the CAPE were significantly higher at M2 (0.8 mg/mL; P = .0012) and M3 (3.7 mg/mL; P = .0014) than the control (0.5 and 0.9 mg/mL) or G3 (0.6 and 1.0 mg/mL), respectively. Histologic examination showed the CAPE group to display more pericapsular tubular necrosis (3.0 [2.0; 3.0]) than the G1 group (2.0 [1.0; 2.0]) or G3 group (1.5 [1.0; 2.0]; P < .001). The CAPE group displayed more medullary tubular necrosis (2.0 [2.0; 3.0] than G1 (2.0 [1.0; 2.0] or G3 (1.0 [0.0; 2.0]; P < .001). CONCLUSION: CAPE promoted greater functional and anatomic renal injury when rats were anesthetized with iso than control or ethanol groups, as demonstrated by histologic analysis and serum values.

Erythropoietin attenuates apoptosis after ischemia-reperfusion-induced renal injury in transiently hyperglycemic Wister rats.

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.