Trimetazidine Reverses Deleterious Effects of Ischemia-Reperfusion in the Isolated Perfused Pig Kidney Model

Abstract

Background: Delayed graft function has remained an important complication after renal transplantation. Methods: The purpose of this study was to evaluate Euro-Collins (EC) plus trimetazidine (TMZ) in comparison with standard EC solution after 24- or 48-hour cold storage. The normothermic isolated perfused pig kidney technique combined with proton nuclear magnetic spectroscopy was used. Results: The study verified that TMZ plus EC had a beneficial preservation effect over EC in terms of better perfusate flow rate at both 24 and 48 h (p < 0.01 and p < 0.001, respectively). In addition, TMZ also was beneficial in terms of increased glomerular filtration rate, better proximal tubular functions, and less tubular injury markers. Lipid peroxidation, evaluated by malondialdehyde renal tissue levels, was decreased in kidney homogenates preserved with TMZ, particularly after 48-hour cold storage. Citrate excretion which reflects a better intracellular pH regulation was detected in urine from kidneys preserved with TMZ. Histological data paralleled findings of the above when comparing cellular injury factors such as vacuolization, necrosis, tubular structure, and interstitial edema. Conclusion: These results indicate that, under the conditions of our experiments, the addition of TMZ to EC solution increased the preservation quality of kidneys particularly after prolonged cold ischemia.

A Model of Isolated Autologously Hemoperfused Porcine Slaughterhouse Kidneys

“…Other recently reported perfusion protocols used blood-free perfusion solutions [15, 36]. A simultaneous dialysis and permanent control of electrolytes, metabolites and base excess has not been reported so far.…”

“…Therefore, the porcine kidney resembled the best approach to investigate perfusion/ischemia-related renal effects [15, 16, 17, 18, 19]. However, the use of porcine organs is expensive and as modern ethical standards demand a significant reduction of animals used for scientific purposes, the models of isolated porcine kidneys did not reach a widespread use so far.…”

Studies on Calcium Oxalate Binding Proteins: Effect of Lipid Peroxidation

“…Crystal growth inhibitors such as citric acid do not have remarkable effect on crystal retention, while phytic-acid-diminished calcium oxalate crystal retention in the membrane [23]also suggests that peroxidation of proteins plays a role in the retention and formation of large aggregates. Peroxidised proteins form aggregated COM crystals and intertwined COD crystals, which mimics crystalluria in hyperoxaluria.…”

Stimulation of Carnitine Palmitoyltransferase 1 Improves Renal Function and Attenuates Tissue Damage After Ischemia/Reperfusion

“…2B). Serum concentrations of AST and LDH are directly proportional to severity of the tissue damage and are commonly used as markers for cellular injury [21][22][23][24]. While AST and LDH levels increased 6.7-and 13.1-fold respectively after I/R compared to the sham group (Figs.…”