Tadalafil protector effect during ischemia-reperfusion in rats

Abstract Purpose: To evaluate histological parameters in rat renal tissue after tadalafil use during hot ischemia for 45 minutes and reperfusion for 24 hours. Methods: Twenty rats were divided into 2 groups. In the experimental group 10 mg/kg of tadalafil was used per gavage before the procedure. All cases underwent left partial nephrectomy, followed by 45 minutes of warm ischemia. Left nephrectomy of the remaining kidney was performed after 24 hours from the initial procedure. The histological parameters analyzed were: detachment of tubular cells, accumulation of desquamated cells in the proximal tubule, loss of brush border, tubular cylinders, interstitial edema, leukocyte infiltration, capillary congestion, vacuolization, tubular dilatation, necrosis and collapse of the capillary tuft. Results: Two rats from each group died and were excluded from the study. Tadalafil significantly reduced leukocyte infiltration (p = 0.036). The remaining histological parameters did not show statistical difference between the groups. Conclusion: The use of tadalafil during warm ischemia and reperfusion demonstrates statistically significant reduction of leukocyte infiltration in the renal interstitium.

Influence of chlorpromazine on renal histology of rats submitted to ischemia and reperfusion injury

ABSTRACT PURPOSE: To analyze the influence of chlorpromazine on renal histology of rats submitted to ischemia and reperfusion injury. METHODS: Sixteen Wistar rats - split in two groups - have been used: control group, receiving 3 mg/kg isotonic saline solution through caudal vein, and, the chlorpromazine group, receiving 3 mg/kg-IV of such medication. The nephrectomy of the left kidney lower third was carried out; immediately, the test-drug was administrated. After 15 minutes of test-drug administration, the renal pedicle was clamped; in 60 minutes of ischemia it was released. After 24 hours of the renal reperfusion, the rats were, once more, anesthetized and submitted to total left nephrectomy, and, afterwards, to euthanasia. Histological findings regarding ischemia have been evaluated and compared between the groups. RESULTS: There was no statistical difference related to inferior renal pole histological analysis. Regarding 60-minute renal ischemia, chlorpromazine has statistically reduced the accrual of leucocytes within the vasa recta renis (p=0.036) and the congestion of peritubular capillaries (p=0.041). When conducting joint analysis of histological patterns, the control group showed a median score of 11 and chlorpromazine group of 5.5 (p=0.036). CONCLUSION: Chlorpromazine significantly reduced the occurrence of secondary damage to ischemia and reperfusion process in the overall histological analysis.

Effects of immunosuppression with tacrolimus and mycophenolate mofetil on renal histology and function in single kidney rats submitted to ischemia and reperfusion

PURPOSE: To evaluate renal histological changes and renal function in single kidney rats submitted to renal ischemia-reperfusion and to immunosuppression with tacrolimus and mycophenolate-mofetil. METHODS: Experimental study with 80 Wistar rats distributed into control, Sham and six other groups treated with immunosuppressive drugs. Animals undergoing surgery, right nephrectomy and left renal clamping, killed on the 14th day and analyzed for renal histology, urea and creatinine. RESULTS: The group receiving tacrolimus at higher doses (T3) showed renal histological lesions indicative of early nephrotoxicity, and significant increase in urea and creatinine. The group M (mycophenolate-mofetil alone) and the group M2 (mycophenolate-mofetil combined with half the usual dose of tacrolimus) presented a slight rise in serum urea. The groups using mycophenolate-mofetil alone or combined with tacrolimus showed creatinine levels similar to that of the group T3. CONCLUSIONS: Histologically, the association of injury by ischemia-reperfusion with the use of tacrolimus or mycophenolate-mofetil alone demonstrated a higher rate of renal changes typical of early nephrotoxicity. In laboratory, the combination of injury by ischemia-reperfusion with tacrolimus at higher doses proved to be nephrotoxic. .

Analysis of the histology of the scar bladder and biochemical parameters of rats with a solitary kidney undergoing immunosuppression with tacrolimus

PURPOSE: To evaluate bladder histology in healing and biochemical analysis of rats with single kidney in ischemia/reperfusion, treated with tacrolimus. METHODS: Fifty rats randomized into five groups. Three rats died in surgery, 47 rats divided in groups: Control (non-operated, n=10), Sham (operated without drugs, n=8), T1 (operated + tacrolimus 1mg/kg, n=10), T2 (operated + tacrolimus 0.1 mg/kg, n=10), T3 (operated + tacrolimus 10mg/kg, n=9). The surgery was: laparotomy, right nephrectomy, left kidney ischemia/reperfusion, cystotomy followed by bladder suture. After that, rats were submited to gavage daily (Control and Sham with saline solution. T1, T2, T3 with tacrolimus in doses already mentioned). On the 14th day, after death induction, cystectomy was performed and bladder was histologicaly analysed. The serum urea, creatinine and tacrolimus were analysed too. RESULTS: There was difference in serum tacrolimus in T3 compared to the other groups (p<0.05). There was higher doses of creatinine in T3 group and higher urea in groups with tacrolimus. There were significant differences among all histologic variables comparing groups with and without tacrolimus (p<0.05). CONCLUSION: Tacrolimus associated with ischemia/reperfusion is nephrotoxic, suppresses inflammation and seems to delay the healing bladder. .