Pediatric Nephrology

, Volume 8, Issue 4, pp 447–450 | Cite as

Transplacental effects of gentamicin on endocytosis in rat renal proximal tubule cells

  • Hatem Smaoui
  • Madeleine Schaeverbeke
  • Jean-Pierre Mallié
  • Jean Schaeverbeke
Original Article

Abstract

Changes in kidney maturation in utero have been reported after gentamicin administration to pregnant rats. While the proteinuria commonly observed, could be related to modifications of the glomerular basement membrane, perturbed renal protein handling could be accounted for by changes in the proximal tubular cells. Therefore, we studied the effect of gentamicin on the renal handling and transport of proteins in proximal tubular cells using the horseradish peroxidase, a fluid-phase marker, as a probe. Gentamicin was administered intraperitoneally to pregnant Wistar rats (75 mg/kg body weight per day) and neonatal kidneys were studied 1 day after birth. In proximal tubular cells of the deep cortical area, containing the fully matured nephrons of neonates, the transport and digestion of reabsorbed peroxidase was considerably reduced compared with controls where peroxidase reached lysosomes after endocytosis. Urinary protein excretion increased in treated animals. We conclude that gentamicin, entering the proximal tubular cells via the endocytic pathway, decreases the tubular reabsorption of proteins, thus increasing urinary protein excretion.

Key words

Gentamicin Proximal tubular cells Endocytosis Gestation Neonate 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Palco FG, Smith MM, Anieri GM (1969) Nephrotoxicity of aminoglycoside and gentamicin. J Infect Dis 119: 406–409Google Scholar
  2. 2.
    De Broe ME, Paulus GJ, Verpooten GA, Roels F, Buyssens N, Wedden R, Van Hoof F, Tulkens PM (1984) Early effects of gentamicin, tobramycin and amikacin on the human kidney. Kidney Int 25: 643–652Google Scholar
  3. 3.
    Provoost AP, Adejuyighe O, Wolf ED (1985) Nephrotoxicity of aminoglycosides in young and adult rats. Pediatr Res 19: 1191–1196Google Scholar
  4. 4.
    Houghton DC, Hartnett M, Campbell-Boswell M, Porter G, Bennet WM (1976) A light and electron microscopic analysis of gentamicin nephrotoxicity in rats. Am J Pathol 82: 589–612Google Scholar
  5. 5.
    Collier VU, Lietman PS, Mitch WE (1979) Evidence for luminal uptake of gentamicin in the perfused rat kidney. J Pharmacol Exp Ther 210: 247–251Google Scholar
  6. 6.
    Silverblatt FJ, Kuehn C (1979) Autoradiography of gentamicin uptake by the rat proximal tubule cell. Kidney Int 15: 335–345Google Scholar
  7. 7.
    Sastrasinh M, Knauss TC, Weinberg JM, Humes D (1982) Identification of the aminoglycoside binding site in rat renal brush border membranes. J Pharmacol Exp Ther 222: 350–358Google Scholar
  8. 8.
    Vandevalle A, Farman N, Morin JP, Fillastre JP, Hatt PY, Bonvalet JP (1981) Gentamicin incorporation along the nephron: autoradiographic study on isolated tubules. Kidney Int 19: 529–539Google Scholar
  9. 9.
    Feldman S, Wang MY, Kaloyanides GJ (1982) Aminoglycosides induce a phospholipidosis in the renal cortex of the rat: an early manifestation of nephrotoxicity. J Pharmacol Exp Ther 220: 514–520Google Scholar
  10. 10.
    Hosteter KY, Hall LB (1989) Inhibition of kidney lysosomal phospholipase A and C by aminoglycoside antibiotic: possible mechanism of aminoglycoside toxicity. Proc Natl Acad Sci USA 79: 1663–1663Google Scholar
  11. 11.
    Toubeau G, Maldague P, Laurent G, Vaamonde CA, Tulkens PM, Hueson Stiennon JA (1986) Morphological alterations in distal and collecting tubules of the rat renal cortex after aminoglycoside administration at low doses. Virchows Arch [B] 51: 475–485Google Scholar
  12. 12.
    Bayliss C, Rennke HG, Brenner BM (1977) Mechanisms of the defects in glomerular ultrafiltration associated with gentamicin administration. Kidney Int 12: 344–353Google Scholar
  13. 13.
    Welwood JM, Lovell D, Thompson AE, Tighe JR (1976) Renal damage caused by gentamicin: a study of the effects on renal morphology and urinary enzyme excretion. J Pathol 118: 171–182Google Scholar
  14. 14.
    Schentag JJ, Sutfin TA, Plant ME, Jusko WJ (1978) Early detection of aminoglycoside nephrotoxicity with urinary β2 microglobulin. J Med 9: 201–210Google Scholar
  15. 15.
    Bennet WM (1983) Aminoglycoside nephrotoxicity. Nephron 35: 73–77Google Scholar
  16. 16.
    Humes HD (1988) Aminoglycoside nephrotoxicity. Kidney Int 33: 900–911Google Scholar
  17. 17.
    Kaloyanides GJ, Pastoria-Munoz E (1980) Aminoglycoside nephrotoxicity. Kidney Int 18: 571–582Google Scholar
  18. 18.
    Gilbert T, Nabarra B, Merlet-Benichou C (1988) Light and electron-microscopic analysis of the kidney in newborn rats exposed to gentamicin in utero. Am J Pathol 130: 33–43Google Scholar
  19. 19.
    Mallié JP, Coulon G, Billerey C, Faucourt A, Morin JP (1988) In utero aminoglycosides induced nephrotoxicity in rat neonates. Kidney Int 33: 36–44Google Scholar
  20. 20.
    Mallié JP, Gerard H, Gerard A (1984) Gentamicin administration to pregnant rats: effect on fetal renal development in utero Dev Pharmacol Ther 7 [Suppl 1]: 89–92Google Scholar
  21. 21.
    Mallié JP, Gerard H, Gerard A (1986) In-utero gentamicin-induced nephrotoxicity in rats. Pediatr Pharmacol 5: 229–239Google Scholar
  22. 22.
    Smaoui H, Mallié JP, Cheignon M, Borot C, Schaeverbeke J (1991) Glomerular alterations in rat neonate after transplacental exposure to gentamicin. Nephron 59: 626–631Google Scholar
  23. 23.
    Smaoui H, Mallié JP, Schaeverbeke M, Robert A, Schaeverbeke J (1993) Gentamicin administered during gestation alters glomerular basement membrane development. Antimicrob Agents Chemother 37: 1510–1517Google Scholar
  24. 24.
    Tessin I, Bergmack J, Hiesche K, Jagenburg R, Trollfors B (1982) Renal functions of neonates during gentamicin treatment. Arch Dis Child 57: 758–760Google Scholar
  25. 25.
    Cowan RH, Jukkola AF, Arant BS Jr (1980) Pathophysiologic evidence of gentamicin nephrotoxicity in neonatal puppies. Pediatr Res 14: 1204–1211Google Scholar
  26. 26.
    Yoshioka H, Monna T, Matsuda (1972) The placental transfer of gentamicin. J Pediatr 80: 121–123Google Scholar
  27. 27.
    Slot JW, Gueuze HJ (1981) Sizing of protein A-colloidal probes for immunoelectron microscopy. J Cell Biol 90: 533–541Google Scholar
  28. 28.
    Lowry OH, rosebrough NJ, Farr AL, Randall RJ (1951) Protein measuirement with the folin phenol reagent. J Biol Chem. 193: 265–275Google Scholar
  29. 29.
    Wedeen RP, Batuman V, Cheeks C, Marquet E, Sobel H (1983) Transport of gentamicin in rat proximal tubule. Lab Invest 48: 212–223Google Scholar
  30. 30.
    Schaeverbeke J, Cheignon M (1980) Differentiation of glomerular filter and tubular reabsorption apparatus during fetal development of the rat kidney. J Embryol Exp Morphol 58: 157–175Google Scholar

Copyright information

© IPNA 1994

Authors and Affiliations

  • Hatem Smaoui
    • 1
  • Madeleine Schaeverbeke
    • 1
  • Jean-Pierre Mallié
    • 2
  • Jean Schaeverbeke
    • 1
  1. 1.Laboratoire de Biologie CellulaireUniversité Paris 7Paris Cedex 05France
  2. 2.Laboratoire de NéphrologieUniversité de Nancy IVandoeuvre CedexFrance

Personalised recommendations