PURPOSE: To study the role of pentoxifylline (PTX) on remote kidney injury caused by muscle ischemia of left hindlimb of rats. METHODS: After xylazine and ketamine anesthesia, the left hindlimb of rats (n=66) were submitted to 6 hours ischemia (clamping the left common iliac artery). Three groups were used: sham group (SG, n=6), early group (EG, n=30) with reperfusion after 4 hours and late group (LG, n=30) with reperfusion after 24 hours. The saline solution (EG1, n=10 and LG1, n=10) or PTX (40mg.Kg-1) was administered in the reperfusion beginning (EG2, n=10/LG2, n=10) or divided in two doses in the ischemia beginning and reperfusion beginning (EG3, n=10/LG3, n=10). The plasmatic creatinokinase, urea, creatinine, sodium and potassium values were measure and histological samples from left kidney were prepared and H&E stained for scored cellular necrosis and degeneration of kidney tubules and thickness glomerulus determination. The apoptosis index was determined by immunohistochemical expression of the caspase-3. The tests of Mann-Whitney and Kruskal-Wallis (p < 0.05) were applied. RESULTS: The urea (90.5 ± 30.96 mg.dL-1), creatinine (2.28 ± 0.54 mg.dL-1), potassium (16 ± 3.66 mmol.dL-1) and mesangium thickness (0.97 ± 0.42 µm) values were significantly higher in group LG3. There was no significantly difference of caspase 3 expression between EG2 (16.35 ± 1.65%) and LG3 (15.57 ± 2.54%), and both were significantly worse than SG (9.8 ± 1.98%). CONCLUSIONS: The PTX has some protecting effect on remote kidney injury due to hindlimb ischemia/reperfusion injury only in the early phase of reperfusion.

CONTEXTO: A reperfusão de músculo esquelético piora as lesões já presentes no período de isquemia, pois a produção de espécies reativas de oxigênio, associadas à intensa participação de neutrófilos, amplia a reação inflamatória que induz alterações teciduais. OBJETIVO: Avaliar as alterações morfológicas e imuno-histoquímicas de músculo esquelético (sóleo) de ratos submetidos a isquemia e reperfusão com pentoxifilina. MÉTODOS: Sessenta ratos foram submetidos a isquemia do membro pélvico, por 6 horas, pelo clampeamento da artéria ilíaca comum esquerda. Após isquemia, os animais do grupo A (n = 30) foram observados por 4 horas, e os do grupo B (n = 30), por 24 horas. Seis animais constituíram o grupo simulado. Administrou-se pentoxifilina apenas no período de reperfusão em A2 (n = 10) e B2 (n = 10) e nos períodos de isquemia e reperfusão em A3 (n = 10) e B3 (n = 10). O músculo sóleo foi avaliado por análise histológica (dissociação de fibras, infiltrado leucocitário, necrose) e imuno-histoquímica (apoptose pela expressão da caspase-3). Foram aplicados os testes não-paramétricos de Kruskal-Wallis e Mann-Whitney (p < 0,05). RESULTADOS: As alterações foram mais intensas no grupo B1, com médias de escore da dissociação de fibras musculares de 2,16 ± 0,14, infiltrado neutrofílico de 2,05 ± 0,10 e expressão da caspase-3 na área perivascular de 4,30 ± 0,79; e menos intensas no grupo A3, com respectivas médias de 0,76 ± 0,16, 0,92 ± 0,10 e 0,67 ± 0,15 (p < 0,05). A caspase-3 mostrou-se mais expressiva no grupo B1 na área perivascular, com média de 4,30 ± 0,79, em comparação com o grupo B1 na área perinuclear, com média de 0,91 ± 0,32 (p < 0,05). CONCLUSÕES: As lesões são mais intensas quando o tempo de observação é maior após a reperfusão, e a pentoxifilina atenua essas lesões, sobretudo quando usada no início das fases de isquemia e de reperfusão.

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Acute renal failure (ARF) is an extremely important public health issue in need of novel therapies. The present study aimed to evaluate the capacity of mesenchymal stem cell (MSC) therapy to promote the improvement and recovery of renal function in a preclinical model. Wistar rats were used as the experimental model, and our results show that cisplatin (5mg/kg) can efficiently induce ARF, as measured by changes in biochemical (urea and creatinine) and histological parameters. MSC therapy performed 24h after the administration of chemotherapy resulted in normalized plasma urea and creatinine levels 30 and 45d after the onset of kidney disease. Furthermore, MSC therapy significantly reduced histological changes (intratubular cast formation in protein overload nephropathy and tubular hydropic degeneration) in this ARF model. Thus, considering that current therapies for ARF are merely palliative and that MSC therapy can promote the improvement and recovery of renal function in this model system, we suggest that innovative/alternative therapies involving MSCs should be considered for clinical studies in humans to treat ARF.

PURPOSE:To investigate the small intestinal tissue alterations in rats submitted to ischemia and tissue reperfusion using pentoxyfilline or prostaglandin E1. METHODS:Thirty five Wistar rats were used, distributed into group control (A) n=10 were submitted to intestinal ischemia and reperfusion during 60 minutes and no one drug have been utilized. In the group pentoxyfilline (B) n=10 have been utilized during tissue ischemia and reperfusion as well as prostaglandin E1 (C) n=10, but separately . In the group sham (D) n=5, the animals were submitted to surgical. After euthanasia of the animals, a segment of the small intestine was cut, stained by hematoxilin-eosin and histological analysis according to Chiu criteria. RESULTS:Histological results showed that using pentoxyflline or prostaglandin E1 the results during tissue reperfusion were better, since the levels of criteria from Chiu that predominated were level 2 and 3, indicating less tissue damage in comparison to the control group (group A) that showed levels 4 and 5, what means more severe histological tissue alterations. CONCLUSION:Use of pentoxyfilline or prostaglandin E1 promoted a beneficial effect during intestinal reperfusion, demonstrated by less severe histological lesions in the small intestine mucosa of rats submitted to ischemia and tissue reperfusion when helped by the drugs.