Nephrotoxicity pp 303-308 | Cite as

Cyclosporine A-induced Lipid Peroxidation in Rat Renal Microsomes and Effect on Glucose Uptake by Renal Brush Border Membrane Vesicles

  • G. Inselmann
  • M. Blank
  • K. Baumann

Abstract

Nephrotoxicity is the most important side effect of cyclosporine A (CsA) treatment and has been well documented in patients and experimental animals (1). The nature of CsA-induced renal damage is complex and the precise mechanism is still unclear. Some possible pathogenetic mechanisms have already been investigated. There is convincing evidence that a direct CsA effect on tubular cell could also contribute to CsA nephrotoxicity (2). CsA is taken up by isolated proximal tubule segments in a rapid, time-dependent and saturable manner (3). A saturable binding of CsA to isolated rat renal brush border membranes was also shown. This binding may be best explained by a partitioning process of the lipophilic CsA into the phospholipid phase of the cell membrane rather than binding to a specific membrane component. These findings demonstrate that CsA has the ability to interact with renal tubular cell membranes, even at low concentrations, and therefore has a distinct potential for toxic effects on renal cells. The aim of the present study was to investigate in vitro whether or not CsA induces lipid peroxidation in isolated rat renal microsomes and moreover to evaluate the influence of CsA on glucose uptake by rat renal brush border membrane vesicles. To the best of our knowledge there appeared only one report regarding to CsA-induced nephrotoxicity and lipid peroxidation.

Keywords

Brush Border Membrane Brush Border Membrane Vesicle Microsomal Lipid Peroxidation Renal Brush Border Membrane Renal Cortical Slice 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    R. Y. Calne, S. Thiru, P. McMaster, G. N. Craddock, D. J. G. White, D. B. Evans, D. C. Dunn, B. D. Pentlow and K. Rolles, Cyclosporin A in patients receiving renal allografts from cadaver donors. Lancet, 2: 1323 (1978).PubMedCrossRefGoogle Scholar
  2. 2.
    C. Cunningham, M. Gavin, P. H. Whiting, M. D. Burke, F. Macintyre, A. W. Thomson and J. G. Simpson, Serum cyclosporin levels, hepatic drug metabolism and renal tubulotoxicity. Biochem. Pharmacol., 33: 2857 (1984).PubMedCrossRefGoogle Scholar
  3. 3.
    N. M. Jackson, R. P. O’Connor and H. D. Humes, Cyclosporine (Cs) interactions with renal proximal tubule cells (PTC) and subcellular membranes. Clin. Res., 33: 487A (1985).Google Scholar
  4. 4.
    Y. Aso, A. Tajima, K. Suzuki, Y. Ohtawara, N. Ohta, M. Hata and T. Tsukada, Nephrotoxicity in rats receiving cyclosporine. Biochemical and morphological study. Nippon Hinyokika Gakkai Zasshi, 76: 1454 (1985).PubMedGoogle Scholar
  5. 5.
    B. Ryffel, P. Donatsch, M. Madorin, B. E. Matter, G. Ruttimann, H. Schon, R. Stoll and J. Wilson, Toxicological evaluation of cyclosporin A. Arch. Toxicol., 53: 107 (1983).PubMedGoogle Scholar
  6. 6.
    T. Bertani, N. Perico, M. Abbate, C. Battaglia and G. Remuzzi, Renal injury induced by long-term administration of cyclosporin A to rats. Am. J. Pathol., 127: 569 (1987).PubMedGoogle Scholar
  7. 7.
    C. De Duve, B. C. Pressman, R. Gianetto, R. Wattiaux and F. Appelmans, Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat liver tissue. Biochem. J., 60: 604 (1955).Google Scholar
  8. 8.
    B. Sedgwick and G. Hubscher, Metabolism of Phospholipids IX. Phosphatidate phosphohydrolase in rat liver. Biochim. Biophys. Acta, 106: 63 (1965).PubMedCrossRefGoogle Scholar
  9. 9.
    J. A. Buege and S. D. Aust, Microsomal lipid peroxidation. Methods Enzvmol., 52: 302 (1978).CrossRefGoogle Scholar
  10. 10.
    C. Cojocel, K. H. Laeschke, G. Inselmann and K. Baumann, Inhibition of cephaloridine-induced lipid peroxidation. Toxicology, 35: 295 (1985).PubMedCrossRefGoogle Scholar
  11. 11.
    R. J. Cross and J. V. Taggart, Renal tubular transport. Accumulation of p-aminohippurate by rabbit kidney slices. Am. J. Physiol., 161: 181 (1950).PubMedGoogle Scholar
  12. 12.
    J. Bibez, B. Stieger, W. Haase and H. Murer, A high yield preparation for rat kidney brush border membranes. Different behaviour of lysosomal markers. Biochim. Biophys. Acta, 647: 169 (1981).CrossRefGoogle Scholar
  13. 13.
    M. E. Blank, F. Bode, E. Huland, D. F. Diedrich and K. Baumann, Kinetic studies of D-glucose transport in renal brush border membrane vesicles of streptozotocin-induced diabetic rats. Biochim. Biophys. Acta, 844: 314 (1985).PubMedCrossRefGoogle Scholar
  14. 14.
    P. H. Whiting, A. W. Thomson, J. T. Blair and J. G. Simpson, Experimental cyclosporine A nephrotoxicity. Br. J. Exp. Path., 63: 88 (1982).Google Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • G. Inselmann
    • 1
  • M. Blank
    • 1
  • K. Baumann
    • 1
  1. 1.Department of Cell Physiology, Institute of PhysiologyUniversity of HamburgHamburg 13Germany

Personalised recommendations