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OtherRENAL PHARMACOLOGY

Effects of Trimetazidine on Lipid Peroxidation and Phosphorus Metabolites during Cold Storage and Reperfusion of Isolated Perfused Rat Kidneys

Th. Hauet, G. Bauza, J. M. Goujon, J. C. Caritez, M. Carretier, M. Eugene and J. P. Tillement
Journal of Pharmacology and Experimental Therapeutics June 1998, 285 (3) 1061-1067;
Th. Hauet
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G. Bauza
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J. M. Goujon
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J. C. Caritez
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M. Carretier
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M. Eugene
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J. P. Tillement
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Abstract

This study was undertaken to evaluate the effect of trimetazidine (TMZ) during cold storage (CS) and the consequence during normothermic reperfusion in an isolated perfused rat kidney model (IPK). IPK was used to assess the rate of perfusion flow, the ratio of ATP to inorganic phosphate (ATP/Pi) as a reflection of the energetic status during reperfusion, intracellular pH (pHi), tissue water content and malondialdehyde (MDA) tissue levels in four different preservation solutions after 48-hr preservation at 4°C and 2-hr reperfusion at 37.5°C: EuroCollins (EC), University of Wisconsin (UW), EC plus TMZ (10−6 M) (EC + TMZ) and UW plus TMZ (10−6 M) (UW + TMZ). When TMZ was added to the preservation solutions, perfusion flow rate (PFR) was significantly improved during reperfusion. Tissue water content, which reflected tissue edema, was significantly lower in TMZ groups than in groups without TMZ during both CS and reperfusion conditions. In TMZ groups, ATP/Pi ratio was also significantly improved during CS and reperfusion. In addition, TMZ lowered the pHi both during preservation and after reperfusion. MDA renal tissue level significantly decreased with TMZ both during the preservation period and after reperfusion. These overall results strongly suggested that TMZ contributes to renal protection from cold ischemia-reperfusion injury in this IPK model, especially when TMZ was added to UW solution and during prolonged hypothermic ischemia.

Footnotes

  • Send reprint requests to: Dr. Th. Hauet, Service de Nephrologie, Hôpital Saint Louis, Centre Hospitalier de La Rochelle, 17019 La Rochelle, France.

  • ↵1 This work was supported by grants from the Ministère de la Recherche (92C0746) and de l’Education Nationale (EA 427), the Association pour le developpement de la Dialyse àDomicile (ADA 17) and the Institut de Recherches Internationales SERVIER.

  • Abbreviations:
    ATP/Pi
    ATP to inorganic phosphate ratio
    CS
    cold storage
    IPK
    isolated perfused rat kidney
    EC
    EuroCollins solution
    EC + TMZ
    EuroCollins solution plus trimetazidine
    MDA
    malondialdehyde
    PCr
    phosphocreatine
    Pi
    inorganic phosphate
    pHi
    intracellular pH
    PFR
    perfusion flow rate
    NMR
    nuclear magnetic resonance
    ROS
    reactive oxygen species
    TMZ
    trimetazidine
    UW
    University of Wisconsin solution
    UW + TMZ
    University of Wisconsin solution plus trimetazidine
    • Received September 4, 1997.
    • Accepted January 20, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 285, Issue 3
1 Jun 1998
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OtherRENAL PHARMACOLOGY

Effects of Trimetazidine on Lipid Peroxidation and Phosphorus Metabolites during Cold Storage and Reperfusion of Isolated Perfused Rat Kidneys

Th. Hauet, G. Bauza, J. M. Goujon, J. C. Caritez, M. Carretier, M. Eugene and J. P. Tillement
Journal of Pharmacology and Experimental Therapeutics June 1, 1998, 285 (3) 1061-1067;

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OtherRENAL PHARMACOLOGY

Effects of Trimetazidine on Lipid Peroxidation and Phosphorus Metabolites during Cold Storage and Reperfusion of Isolated Perfused Rat Kidneys

Th. Hauet, G. Bauza, J. M. Goujon, J. C. Caritez, M. Carretier, M. Eugene and J. P. Tillement
Journal of Pharmacology and Experimental Therapeutics June 1, 1998, 285 (3) 1061-1067;
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