Estudo da proteção renal durante a isquemia e reperfusão em ratos com o CAPE (caffeic acid phenethyl ester)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Ischemic postconditioning and subanesthetic S(+)-Ketamine infusion: effects on renal function and histology in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prevention of renal ischemia/reperfusion injury in rats using acetylcysteine after anesthesia with isoflurane

OBJETIVO: Avaliar o efeito da N-acetilcisteína na proteção renal contra lesão de isquemia/reperfusão, quando administrada logo após a indução anestésica, em ratos anestesiados com isoflurano. MÉTODOS: Dezoito ratos Wistar machos pesando mais que 300g foram anestesiados com isoflurano. A jugular interna direita e a carótida esquerda foram dissecadas e canuladas. Os animais foram distribuídos aleatoriamente em GAcetil, recebendo N-acetilcisteína por via intravenosa, 300mg/kg, e GIsot, solução salina. Foi realizada nefrectomia direita e clampeamento da artéria renal esquerda por 45 min. Os animais foram sacrificados após 48h, sendo colhidas amostras sanguíneas após a indução anestésica e ao sacrifício dos mesmos para avaliar a creatinina sérica. Realizou-se histologia renal. RESULTADOS: A variação da creatinina foi 2,33mg/dL ± 2,21 no GAcetil e 4,38mg/dL ± 2,13 no GIsot (p=0,074). Dois animais apresentaram necrose tubular intensa no GAcetil, comparados a cinco no GIsot. Apenas GAcetil apresentou animais livres de necrose tubular (dois) e degeneração tubular (um). CONCLUSÃO: Após isquemia/reperfusão renais, os ratos aos quais se administrou N-acetilcisteína apresentaram menor variação na creatinina sérica e lesões renais mais leves que o grupo controle.

Remifentanil, Isoflurane, and Preconditioning Attenuate Renal Ischemia/Reperfusion Injury in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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.

Comparative study between trimetazidine and ice slush hypothermia in protection against renal ischemia/reperfusion injury in a porcine model

Purpose: The aim of the study was to compare the effects of renal ice slush hypothermia and the use of trimetazidine in the protection against ischemia/reperfusion (I/R) injury.Materials and Methods: Fifteen farm pigs were submitted to left kidney ischemia and right nephrectomy during the same procedure. Animals were divided into three groups. Group 1 was submitted to warm ischemia; Group 2 was submitted to cold ischemia with ice slush; and Group 3 received trimetazidine 20 mg one day and 4 hours before surgery. Ischemia time was 120 minutes in all three groups. Serum creatinine (SCr) and plasma iohexol clearance (CLioh) were measured before surgery and on postoperative days (PODs) 1,3,7, and 14. Semi-quantitative analyses of histological alterations were performed by a pathologist. A p value of < 0.05 was considered significant.Results: All groups showed elevation of serum creatinine in the first week. Serum creatinine was higher in Group 3 in the first and third postoperative days (Mean Cr: 5.5 and 8.1 respectively). Group 2 showed a lower increase in creatinine and a lower decrease in iohexol clearance than the others. Renal function stabilized in the fourteenth POD in all three groups. Analyses of histological alterations did not reach statistical significance between groups.Conclusion: Trimetazidine did not show protection against renal I/R injury in comparison to warm ischemia or hypothermia in a porcine model submitted to 120 minutes of renal ischemia.

Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

FTY720 prevents renal T-Cell infiltration after ischemia/reperfusion injury

Ischemia/reperfusion (I/R) injury, a common early feature in renal transplantation, results from both free radical species generation and local inflammatory responses that attract different types of cells. The interaction with infiltrating leukocytes could promote damage and death of resident renal cells contributing to worsening of renal function. It has been shown that depletion of host T cells protects against kidney damage after I/R injury, although the mechanism is not fully understood. FTY720, a synthetic analog of a natural product extracted from Isaria sincclairii has shown modulatory properties in experimental models of autoimmune disease, transplantation, and I/R injury. FTY720 alters lymphocyte responses to chemokine homing signals, thereby decreasing the number of lymphocytes in inflammatory sites. We evaluated renal function in mice at 3, 5, and 7 days after I/R injury in the presence or absence of FTY720 treatment. FTY720 treatment promoted earlier recovery of renal function associated with a lower number of renal-infiltrating lymphocytes. These findings confirm previous results showing a protective effect of FTY720 in I/R injury models.

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.

Parecoxib reduces renal injury in an ischemia/reperfusion model in rats

To evaluate the effect of parecoxib (an NSAID) on renal function by measuring plasma NGAL (serum neutrophil gelatinase-associated lipocalin) levels in an induced-ischemia rat model. METHODS: Forty male Wistar rats were randomly assigned to one of four groups: Ischemia (I), Ischemia/parecoxib (IP), No-ischemia (NI), and No-ischemia/parecoxib (NIP). Body weight, mean arterial pressure, heart rate, body temperature, NGAL levels, and renal histology were compared across groups. RESULTS: The Ischemia (I) group, which did not receive parecoxib, showed the highest NGAL levels (p=0.001), while the IP group, which received the medication, had NGAL levels similar to those of the non-ischemic (NI and NIP) groups. CONCLUSION: Parecoxib resulted in renal protection in this experimental model.

Dexmedetomidine on renal ischemia-reperfusion injury in rats: assessment by means of NGAL and histology

Background: Ischemic acute kidney injury is a common occurrence in the perioperative period and in critical patients admitted to intensive care units. The reestablishment of blood supply may worsen injury through the ischemia-reperfusion (I/R) mechanism. We investigated the effect of dexmedetomidine on the kidneys of rats subjected to an experimental I/R model. Methods: 34 rats anesthetized with isoflurane was undergone right nephrectomy and randomly assigned to four groups: Control C (saline solution); Dexmedetomidine D (dexmedetomidine); Sham S (saline solution); Sham with Dexmedetomidine SD (dexmedetomidine). The serum levels of neutrophil gelatinase-associated lipocalin (NGAL) were measured at time-points T1 (following stabilization), T2 (ischemia), T3 (reperfusion), T4 (12 h after of I/R). The kidneys were subjected to histological examination. Results: The NGAL levels were significantly higher at T4 compared with T1. Upon histological examination, the left kidneys in groups C and D exhibited a similar extent of cell injury. Conclusion: The levels of NGAL did not indicate either protection against or worsening of kidney injury. Histological examination for acute tubular necrosis showed that dexmedetomidine did not protect the kidneys from I/R.

Does the Choice of the Halogenated Anesthetic Influence Renal Function during Hemorrhagic Shock and Resuscitation?

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caffeic Acid Phenethyl Ester Effects in the Kidney During Ischemia and Reperfusion in Rats Anesthetized with Isoflurane

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Eficácia da solução de cloreto de sódio a 7,5% com e sem dextran 70 a 6% na preservação da função renal de cães hipovolêmicos submetidos à isquemia-reperfusão

JUSTIFICATIVA E OBJETIVOS: As soluções hipertônicas de cloreto de sódio, associadas ou não a colóides hiperoncóticos, podem ser eficazes em proteger o rim em situações de hipovolemia. O objetivo deste estudo foi verificar, em cães, o real benefício dessas soluções sobre a função renal, em vigência de hipovolemia e isquemia do órgão. MÉTODO: em 24 cães, anestesiados com pentobarbital sódico, submetidos à nefrectomia direita e à expansão volêmica com solução de Ringer (1 ml.kg-1.min-1), foram observadas possíveis alterações renais morfo-funcionais após hemorragia de 20 ml.kg-1 e trinta minutos de total isquemia renal esquerda, com posterior reperfusão, além da repercussão renal da administração de soluções de cloreto de sódio 7,5% (SH) e esta em dextran 70 a 6% (SHD). Atributos estudados: FC, PAM, pressão de veia cava inferior, fluxo sangüíneo renal, resistência vascular renal, hematócrito, Na+, K+, osmolaridade plasmática, PaO2, PaCO2 e pH, depuração (para-aminohipurato de sódio - PAH-1, creatinina, osmolar, água livre, Na+, K+), fração de filtração, volume e osmolaridade urinários, excreções urinárias e fracionárias de Na+ e K+ e exame histopatológico do rim. Os atributos foram estudados em três grupos (G1, G2 e G3) e em cinco momentos. RESULTADOS: Houve elevação estatisticamente significativa da pressão arterial média em G2 e G3, da resistência vascular renal em G1, do fluxo sangüíneo renal e da depuração de PAH em G3, da excreção fracionária de Na+ em G2 e G3, das depurações de creatinina, osmolar, de água livre e de Na+ e K+, da excreção urinária de Na+ e K+ e do volume urinário em G3. CONCLUSÕES: A SHD administrada 15 minutos após hemorragia moderada e 30 minutos antes de insulto isquêmico de 30 minutos foi eficiente em proteger o rim de cães das repercussões da isquemia-reperfusão. Não foi constatada alteração histopatológica renal à microscopia óptica.

The effect of 6% Hydroxyethyl starch vs. Ringer's lactate on acute kidney injury after renal ischemia in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)