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

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          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.

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          Some biochemical aspects of the protective effect of trimetazidine on rat cardiomyocytes during hypoxia and reoxygenation.

          This study was undertaken to evaluate the direct cardioprotective effect of trimetazidine (TMZ), an anti-anginal drug devoid of haemodynamic action, on isolated myocytes. Cultured rat ventricular myocytes were treated with the drug 16 h and 1 h before the experiments. The drug-treated cells and control cells were placed in a substrate free medium and submitted in a specially designed device to either normoxia (N4), or hypoxia (150 min, H2.5, or 240 min, H4), or 150 min hypoxia followed by 90 min reoxygenation (HR). The treatment of the cells with TMZ (5 x 10(-4) M) resulted in a significant decrease of lactate dehydrogenase (LDH) leakage (-58% in H2.5, -36% in H4 and -37% in HR). The LDH release provoked by oxidizing agents. H2O2 and 13-s-HpOTrE (13(S)-hydroperoxyoctadecatrienoic acid) during post-hypoxic reoxygenation was also lowered by TMZ. However, this effect reflected the beneficial action of TMZ during hypoxia since the drug was not efficient in altering the LDH leakage induced by the oxidizing agents in normal conditions. Moreover, the hypoxia-induced decrease of ATP content was not affected by TMZ, and resynthesis of ATP during substrate-free reoxygenation was similar in TMZ-treated and control cells. The respiration parameters have been studied in rat heart mitochondria isolated from control and TMZ-treated rats, in the presence or absence of TMZ in the respiration medium (10(-4) M). The main result was a rapid and potent inhibition of palmitoylcarnitine oxidation, when TMZ was added to the respiration medium. The chronic treatment only resulted in a slight alteration of pyruvate oxidation. In conclusion, a pre-treatment of ventricular myocytes with TMZ resulted in an increased cell resistance to hypoxic stress, as evidenced by LDH leakage. This cytoprotective effect of TMZ should not be mediated through an antioxidant activity, but could be related to a modification of lipid metabolism.
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            Evaluation of Injury Preservation in Pig Kidney Cold Storage by Proton Nuclear Magnetic Resonance Spectroscopy of Urine

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              Proton NMR analysis of plasma from renal failure patients: Evaluation of sample preparation and spectral-editing methods


                Author and article information

                S. Karger AG
                November 1998
                02 November 1998
                : 80
                : 3
                : 296-304
                a Groupe de Recherche en Transplantation Multiviscérale (GRTMV) et Institut National de Recherche Agronomique Le Magneraud, Surgères, b Laboratoire de Résonance Magnétique Nucléaire, Hôpital Saint-Louis, Paris, c Laboratoire de Pharmacologie, Faculté de Médecine de Paris XII, Créteil, France
                45190 Nephron 1998;80:296–304
                © 1998 S. Karger AG, Basel

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                Figures: 3, Tables: 2, References: 32, Pages: 9
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