Comparison of Direct and Remote Ischaemic Preconditioning of Renal Ischaemia Reperfusion Injury in Rats.

OBJECTIVE: One of the methods that can be used to prevent ischaemia reperfusion (IR) injury is ischaemic preconditioning. The aim of this study was to evaluate and compare the effects of remote and direct ischaemic preconditioning (RIPC and DIPC) histopathologically in the rat renal IR injury model. METHODS: After obtaining an approval from the Dokuz Eylül University School of Medicine Ethics Committee, 28 Wistar Albino male rats were divided into four groups. In Group I (Sham, n=7), laparotomy and left renal pedicle dissection were performed, but nothing else was done. In Group II (IR, n=7), after 45 minutes of left renal pedicle occlusion, reperfusion lasting 4 hours was performed. In Group III (DIPC+IR, n=7), after four cycles of ischaemic preconditioning applied to the left kidney, renal IR was performed. In Group IV (RIPC+IR, n=7), after three cycles of ischaemic preconditioning applied to the left hind leg, renal IR was performed. All rats were sacrificed, and the left kidney was processed for conventional histopathology. RESULTS: The histopathological injury score of the kidney was significantly lower in the sham group compared with the other groups (p<0.01). The injury scores of the DIPC+IR and RIPC+IR groups were significantly lower than in the IR group (p<0.05). In the RIPC+IR group, the injury score for erythrocyte extravasation was found to be significantly lower than in the DIPC+IR group (p<0.05). CONCLUSION: In the present study, it was demonstrated that both DIPC and RIPC decreased renal IR injury, but RIPC was found to be more effective than DIPC. This protective effect requiresfurther detailed experimental and clinical studies.

Effects of Dexmedetomidine on Renal Ischaemia Reperfusion Injury in Streptozotocin-Induced Diabetic Rats.

OBJECTIVE: The aim of this study was to investigate the effects of dexmedetomidine before and after ischaemia in diabetic rat kidney ischaemia reperfusion (IR) injury in the experimental diabetic rat model. METHODS: Data belonging to 35 rats weighing between 250 and 300 g were analysed. Diabetes mellitus (DM) was induced using streptozotocin. Groups had bilateral renal vasculature clamped for 45 min ischaemia before clamps were removed, and 4 hours reperfusion was applied. Rats were divided into five groups: Group I or nondiabetic sham group (n=7), Group II or diabetic sham group (n=7), Group III or diabetic IR group (n=7), Group IV or diabetic IR+prophylactic Dex P (before ischaemia) (n=7) and Group V or diabetic IR+therapeutic Dex T (following reperfusion) (n=7). Dexmedetomidine was administered at a dose of 100 µg kg-1 intraperitoneally. Histomorphological and biochemical methods were used to assess the blood and tissue samples. RESULTS: The proximal tubule injury score in the control sham group was significantly lower than in other groups. The proximal tubule and total cell damage scores of the diabetic IR group were significantly higher than the diabetic IR+Dex T group, and no significant difference was detected in the diabetic IR+Dex P group. The biochemical parameters of the IR group were significantly increased compared to Groups I and II; however, there was no significant reduction in these parameters in the groups administered dexmedetomidine. CONCLUSION: Although administration of dexmedetomidine after ischaemia in the diabetic rat renal IR model was found to be more effective on the histopathological injury scores compared to preischaemic administration, this study has not shown that dexmedetomidine provides effective and complete protection in DM.

Renal Ischemia/Reperfusion Injury in Diabetic Rats: The Role of Local Ischemic Preconditioning.

BACKGROUND: The aim of this study was to evaluate the effects of local ischemic preconditioning using biochemical markers and histopathologically in the diabetic rat renal IR injury model. METHODS: DM was induced using streptozotocin. Rats were divided into four groups: Group I, nondiabetic sham group (n = 7), Group II, diabetic sham group (n = 6), Group III, diabetic IR group (diabetic IR group, n = 6), and Group IV, diabetic IR + local ischemic preconditioning group (diabetic IR + LIPC group, n = 6). Ischemic renal injury was induced by clamping the bilateral renal artery for 45 min. 4 h following ischemia, clearance protocols were applied to assess biochemical markers and histopathologically in rat kidneys. RESULTS: The histomorphologic total cell injury scores of the nondiabetic sham group were significantly lower than diabetic sham, diabetic IR, and diabetic IR + LIPC groups. Diabetic IR group scores were not significantly different than the diabetic sham group. But diabetic IR + LIPC group scores were significantly higher than the diabetic sham and diabetic IR groups. CONCLUSION: Local ischemic preconditioning does not reduce the risk of renal injury induced by ischemia/reperfusion in diabetic rat model.

Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats.

BACKGROUND AND OBJECTIVES: We investigated the effect of dexmedetomidine on ischemic renal failure in rats. METHODS: In the present study, 26 male adult Wistar albino rats weighting 230-300 g were randomly separated into four groups: sham-operated (n=5), ischemia reperfusion (IR) (IR group, n=7), IR/reperfusion treatment with dexmedetomidine (Dex. R group, n=7) and IR/pre-ischemic treatment with dexmedetomidine (Dex. I group, n=7). In the first group, sham operation was achieved and renal clamps were not applied. For the IR group, renal ischemia was induced by occlusion of the bilateral renal arteries and veins for 60 min followed by reperfusion for 24h. For the Dex. R and Dex. I groups, the same surgical procedure as in the IR group was performed, and dexmedetomidine (100 mcg/kg intraperitoneal) was administrated at the 5th min after reperfusion and before ischemia. At the end of reperfusion, blood samples were drawn, the rats were sacrificed, and the left kidney was processed for histopathology. RESULTS: The blood urea nitrogen (BUN) levels in groups Dex. R and Dex. I were significantly lower than in the IR group (p=0.015, p=0.043), although urine flow was significantly higher in group Dex. R (p=0.003). The renal histopathological score in the IR group was significantly higher than in the other groups. There was no significant difference between the Dex. R and Dex. I groups. CONCLUSIONS: The results were shown that administration of dexmedetomidine reduced the renal IR injury histomorphologically. Administration of dexmedetomidine in the reperfusion period was considered as more effective due to increase in urinary output and decrease in BUN levels.

Comparison of the effects of dexmedetomidine administered at two different times on renal ischemia/reperfusion injury in rats / Comparação dos efeitos de dexmedetomidina administrada em dois momentos diferentes para lesão de isquemia/reperfusão renal em ratos / Comparación de los efectos de la dexmedetomidina administrada en 2 momentos diferentes para lesión de isquemia-reperfusión renal en ratones

Background and objectives: We investigated the effect of dexmedetomidine on ischemic renal failure in rats. Methods: In the present study, 26 male adult Wistar albino rats weighting 230-300 g were randomly separated into four groups: sham-operated (n = 5), ischemia reperfusion (IR) (IR group, n = 7), IR/reperfusion treatment with dexmedetomidine (Dex. R group, n = 7) and IR/pre-ischemic treatment with dexmedetomidine (Dex. I group, n = 7). In the first group, sham operation was achieved and renal clamps were not applied. For the IR group, renal ischemia was induced by occlusion of the bilateral renal arteries and veins for 60 min followed by reperfusion for 24 h. For the Dex. R and Dex. I groups, the same surgical procedure as in the IR group was performed, and dexmedetomidine (100 mcg/kg intraperitoneal) was administrated at the 5th min after reperfusion and before ischemia. At the end of reperfusion, blood samples were drawn, the rats were sacrificed, and the left kidney was processed for histopathology. Results: The blood urea nitrogen (BUN) levels in groups Dex. R and Dex. I were significantly lower than in the IR group (p = 0.015, p = 0.043), although urine flow was significantly higher in group Dex. R (p = 0.003). The renal histopathological score in the IR group was significantly higher than in the other groups. There was no significant difference between the Dex. R and Dex. I groups. Conclusions: The results were shown that administration of dexmedetomidine reduced the renal IR injury histomorphologically. Administration of dexmedetomidine in the reperfusion period was considered as more effective due to increase in urinary output and decrease in BUN levels. .

Justificativa e objetivos: Investigar os efeitos de dexmedetomidina sobre a insuficiência renal isquêmica em ratos. Métodos: No presente estudo, 26 ratos machos adultos, albinos Wistar, com peso 230-300 g, foram randomicamente divididos em quatro grupos: pseudo-operado (n = 5), isquemia-reperfusão (grupo IR, n = 7), IR/tratamento de reperfusão com dexmedetomidina (grupo Dex-R, n = 7) e IR/tratamento pré-isquemia com dexmedetomidina (grupo Dex-I, n = 7). No primeiro grupo, uma pseudo-operação foi feita e clampeamentos renais não foram aplicados. No grupo IR, isquemia renal foi induzida por oclusão das artérias e veias renais bilaterais durante 60minutos seguida por reperfusão durante 24horas. Nos grupos Dex-R e Dex-I, o mesmo procedimento cirúrgico destinado ao grupo IR foi feito e dexmedetomidina (100mcg/kg intraperitoneal) foi administrada cinco minutos após a reperfusão e antes da isquemia. No fim da reperfusão, amostras de sangue foram coletadas, os ratos foram sacrificados e os rins esquerdos processado para histologia. Resultados: Os níveis de nitrogênio ureico no sangue (BUN) dos grupos Dex-R e Dex-I estavam significativamente mais baixos do que os do grupo IR (p = 0,015, p = 0,043), embora o fluxo urinário tenha sido significativamente maior no grupo Dex-R (p = 0,003). O escore histopatológico renal do grupo IR foi significativamente maior do que os dos outros grupos. Não houve diferença significativa entre os grupos Dex-R e Dex-I. Conclusões: Os resultados demonstraram que a administração de dexmedetomidina reduziu histomorfologicamente a lesão de IR renal. A administração de dexmedetomidina durante o período de reperfusão foi considerada como mais eficaz por causa do aumento do débito urinário e da diminuição dos níveis de BUN. .

Justificación y objetivos: investigar los efectos de la dexmedetomidina sobre la insuficiencia renal isquémica en ratones. Métodos: en el presente estudio, 26 ratones machos adultos, albinos Wistar, con un peso de 230-300 g fueron divididos aleatoriamente en 4 grupos: seudooperado (n = 5), isquemia-reperfusión (grupo IR, n = 7), IR/tratamiento de reperfusión con dexmedetomidina (grupo Dex-R, n = 7) e IR/tratamiento preisquemia con dexmedetomidina (grupo Dex-I, n = 7). En el primer grupo, se realizó una seudooperación y no se aplicaron pinzamientos renales. En el grupo IR, la isquemia renal fue inducida por oclusión de las arterias y venas renales bilaterales durante 60 min seguida por reperfusión durante 24 h. En los grupos Dex-R y Dex-I, se llevó a cabo el mismo procedimiento quirúrgico destinado al grupo IR, y la dexmedetomidina (100 µg /kg intraperitoneal) fue administrada 5 min después de la reperfusión y antes de la isquemia. Al final de la reperfusión, fueron recogidas muestras de sangre, los ratones fueron sacrificados y el riñón izquierdo procesado para histología. Resultados: los niveles de nitrógeno ureico en la sangre (BUN) de los grupos Dex-R y Dex-I eran significativamente más bajos que los del grupo IR (p = 0,015; p = 0,043), aunque el flujo urinario era significativamente mayor en el grupo Dex-R (p = 0,003). La puntuación histopatológica renal del grupo IR fue significativamente mayor que la de los otros grupos. No hubo diferencia significativa entre los grupos Dex-R y Dex-I. Conclusiones: los resultados demostraron que la administración de dexmedetomidina redujo histomorfológicamente la lesión de IR renal. La administración de dexmedetomidina durante el período de reperfusión fue considerada más eficaz debido al aumento de producción de orina y a la disminución ...

Evaluation of the effectiveness of sugammadex for verapamil intoxication.

Previous studies have shown that medications from the cyclodextrin family bind to verapamil. The aim of our study was to determine whether sugammadex could bind to verapamil and prevent the cardiovascular toxicity of that drug. Twenty-eight sedated Wistar rats were infused with verapamil at 37.5 mg/kg/h. Five minutes after the start of infusion, the animals were treated with a bolus of either 16 mg/kg, 100 mg/kg or 1000 mg/kg sugammadex. The control group was treated with an infusion without sugammadex. The heart rate and respiratory rate were monitored, and an electrocardiogram was recorded. The primary end-point was the time to asystole. The verapamil infusion continued until the animals arrested. The asystole time for the S16 group was significantly longer compared to those for the control and S1000 groups (p < 0.05). The asystole time for the S1000 group was significantly shorter than those for all of the other groups (p < 0.05). Reflecting these data, there was a near doubling of the mean lethal dose of verapamil from 13.57 mg/kg (S.D. ±8.1) in the saline-treated rats to 22.42 mg/kg (S.D. ±9.9) in the sugammadex 16 group (p < 0.05). However, for the sugammadex 1000 group, the mean lethal dose was found to be 6.28 ± 1.11 mg/kg. This dose is significantly lower than those for all of the other groups (p < 0.05). We found that treatment with 16 mg/kg sugammadex delayed verapamil cardiotoxicity in rats. However, 1000 mg/kg sugammadex accelerated verapamil cardiotoxicity in rats. Further studies must be conducted to investigate the interaction between verapamil and sugammadex.

The effect of insulin treatment on Rac1 expression in diabetic kidney.

This study was designed to evaluate the renoprotective effect of insulin on diabetic nephropathy through Rac1 inhibition. Twenty Wistar rats were divided into three groups: control (C), diabetic (D), and insulin-treated diabetic (D + I). Diabetes was induced by a single streptozotocin (STZ) injection (45 mg/kg i.p.) in adult male rats. Diabetic animals were treated subcutaneously with insulin (6 U/kg), or saline once a day for 8 weeks. Age-matched control rats received only saline. The kidney tissue samples were analyzed by immunohistochemical staining for Rac1 and cleaved caspase-3 expressions and using the TUNEL method for determining apoptotic cells. Diabetes increased the number of TUNEL (+) cells and cleaved caspase-3 and Rac1 expression levels in kidney. Administration of insulin for 8 weeks reduced Rac1 expression and ameliorated histopathological changes in kidney of STZ-induced diabetes model. These results may suggest that the renoprotective effect of insulin at least partly results from inhibition of Rac1 overexpression.