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

Abstract

Brazil. Conception, design, intellectual and scientific content of the study; critical revision. ABSTRACT 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 14 th 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 mycophenolatemofetil 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.

miR-451 on Myocardial Ischemia-Reperfusion in Rats by Regulating AMPK Signaling Pathway

“…During ischemia-reperfusion, neutrophils are activated when they contact endothelial cells and then release some toxic inhibitors, such as antideoxy free radicals, proteases, elastin, and collagenase [ 17 ]. These toxins in human cells may destroy human endothelial connective cells, inhibit the expansion of physiological capillary walls and inhibit antithrombotic cell mechanisms, and may increase the permeability of human capillary walls.…”