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Rabbit Renal Proximal Tubule Suspensions as a Model for Nephrotoxicity Evaluation of Native or in situ Metabolized β-Lactam Antibiotics

  • H. Dutertre-Catella
  • C. Martin
  • M. Debray
  • C. Pham-Huy
  • M. Thevenin
  • J.-M. Warnet
  • R. A. Podevin
  • J. R. Claude
Conference paper
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 17)

Abstract

Rabbit renal proximal tubule suspensions have proved a convenient model for nephrotoxicity studies, particularly for direct nephrotoxins such as Cephaloridin (Olivier et al., 1992). In order to evaluate the ability of this model to metabolize certain drugs to nephrotoxic compounds, we used another B-lactam antibiotic, Imipenem, known to be nephrotoxic through renal metabolism via hydrolysis by dehydropeptidase I (DHP) (Birnbaum et al., 1985). The use of Cilastatin, an inhibitor of this enzyme, should confirm this metabolic pathway.

Keywords

ATPase Activity Energy Charge Total Glutathione Adenosine Triphosphatase Glutathione Disulfide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Atkinson DE (1968) The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry 7: 4030–4034PubMedCrossRefGoogle Scholar
  2. Birnbaum J, Kahan FM & Kropp H (1985) Carbapenems, a new class of beta-lactam antibiotics. Discovery and development of Imipenem/Cilastatin. Amer J Med 78 (suppl 6A): 3–21PubMedCrossRefGoogle Scholar
  3. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254PubMedCrossRefGoogle Scholar
  4. Burg M & Orloff J (1962) Oxygen consumption and active transport in separated renal tubules. Amer J Physiol 203: 327–330PubMedGoogle Scholar
  5. Griffith OW (1980) Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106: 207–212PubMedCrossRefGoogle Scholar
  6. Olivier MF, Martin C, Dutertre-Catella H, Thevenin M, Warnet JM, Vannier B, Claude JR, Podevin RA (1992) Effects of a new Cephalosporin, Cefpirome (HR 810), on ATPase activities of rabbit renal proximal tubule suspensions: comparison with Cephaloridine and Cefotaxime. Toxicol in vitro 6: 175–176PubMedCrossRefGoogle Scholar
  7. Pham-Huy C, Martin C, Thevenin M, Warnet JM, Ellouk S, Massicot F, Dutertre- Catella H, Claude JR (1993) Determination of ATP, ADP, AMP and other nucleotides in tissues and cell cultures by HPLC. Pharmacol Toxicol 73 (suppl II): 120Google Scholar
  8. Podevin RA & Parini A (1989) Adrenergic agonists and the Na+,K+-adenosine triphosphatase from rabbit proximal tubules and the basolateral membranes. J Pharmacol Exp Ther 250: 672–677PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • H. Dutertre-Catella
    • 1
  • C. Martin
    • 1
  • M. Debray
    • 2
  • C. Pham-Huy
    • 1
  • M. Thevenin
    • 1
  • J.-M. Warnet
    • 1
  • R. A. Podevin
    • 3
  • J. R. Claude
    • 1
  1. 1.Laboratoire de Toxicologie (EA 207)Faculté de PharmacieParis Cedex 06France
  2. 2.Laboratoire de MathématiquesFaculté de PharmacieParis Cedex 06France
  3. 3.INSERM U 356ParisFrance

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