PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of aacPermissionsJournals.ASM.orgJournalAAC ArticleJournal InfoAuthorsReviewers
 
Antimicrob Agents Chemother. 1994 February; 38(2): 189–194.
PMCID: PMC284424

Subcellular distribution of daptomycin given alone or with tobramycin in renal proximal tubular cells.

Abstract

Previous studies in experimental animals showed that daptomycin, a lipopeptide antibiotic, protects against aminoglycoside nephrotoxicity (C. A. Wood, H. C. Finkbeiner, S. J. Kohlhepp, P. W. Kohnen, and D. N. Gilbert, Antimicrob. Agents Chemother. 33:1280-1285, 1989; D. Beauchamp, M. Pellerin, P. Gourde, M. Pettigrew, and M. G. Bergeron, Antimicrob. Agents Chemother. 34:139-147, 1990). In order to better understand the mechanism involved in this protective effect, the subcellular distribution of daptomycin was investigated in the proximal tubular cells of animals treated with daptomycin alone or in combination with tobramycin. A first group of female Sprague-Dawley rats received a single intravenous injection of daptomycin at a dose of 100 mg/kg of body weight and were killed at 10 min, 1 h, or 24 h after the injection. Other groups of rats were treated during 10 days with saline (NaCl, 0.9%), tobramycin at dosages of 20 mg/kg/12 h, daptomycin at dosages of 10 mg/kg/12 h, or the combination tobramycin-daptomycin at the same dosages. At the time of sacrifice, the renal cortex of the right kidney of each animal was dissected, and small blocks of tissue were fixed, dehydrated, and embedded in Araldite 502 epoxy resin. The subcellular distribution of daptomycin and tobramycin was determined on ultrathin sections by immunogold labeling. Ten minutes after the injection of daptomycin alone, gold particles were seen over the brush border membrane and on the membranes of the endocytic vacuoles of proximal tubular cells. One hour after the injection, a similar distribution was seen and numerous gold particles were found over the lysosomes of proximal tubular cells. The results suggest that daptomycin might protect against aminoglycoside nephrotoxicity by interfering with the interaction between the aminoglycoside and phospholipids inside the lysosomes of proximal tubular cells.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Beauchamp D, Gourde P, Bergeron MG. Subcellular distribution of gentamicin in proximal tubular cells, determined by immunogold labeling. Antimicrob Agents Chemother. 1991 Nov;35(11):2173–2179. [PMC free article] [PubMed]
  • Beauchamp D, Gourde P, Simard M, Bergeron MG. Subcellular localization of tobramycin and vancomycin given alone and in combination in proximal tubular cells, determined by immunogold labeling. Antimicrob Agents Chemother. 1992 Oct;36(10):2204–2210. [PMC free article] [PubMed]
  • Beauchamp D, Pellerin M, Gourde P, Pettigrew M, Bergeron MG. Effects of daptomycin and vancomycin on tobramycin nephrotoxicity in rats. Antimicrob Agents Chemother. 1990 Jan;34(1):139–147. [PMC free article] [PubMed]
  • Bergeron MG, Marois Y, Kuehn C, Silverblatt FJ. Autoradiographic study of tobramycin uptake by proximal and distal tubules of normal and pyelonephritic rats. Antimicrob Agents Chemother. 1987 Sep;31(9):1359–1364. [PMC free article] [PubMed]
  • Giurgea-Marion L, Toubeau G, Laurent G, Heuson-Stiennon JA, Tulkens PM. Impairment of lysosome-pinocytic vesicle fusion in rat kidney proximal tubules after treatment with gentamicin at low doses. Toxicol Appl Pharmacol. 1986 Nov;86(2):271–285. [PubMed]
  • Roth J. The preparation of protein A-gold complexes with 3 nm and 15nm gold particles and their use in labelling multiple antigens on ultra-thin sections. Histochem J. 1982 Sep;14(5):791–801. [PubMed]
  • Roth J, Bendayan M, Orci L. Ultrastructural localization of intracellular antigens by the use of protein A-gold complex. J Histochem Cytochem. 1978 Dec;26(12):1074–1081. [PubMed]
  • Silverblatt FJ, Kuehn C. Autoradiography of gentamicin uptake by the rat proximal tubule cell. Kidney Int. 1979 Apr;15(4):335–345. [PubMed]
  • Tapia FJ, Varndell IM, Probert L, De Mey J, Polak JM. Double immunogold staining method for the simultaneous ultrastructural localization of regulatory peptides. J Histochem Cytochem. 1983 Jul;31(7):977–981. [PubMed]
  • Wood CA, Finkbeiner HC, Kohlhepp SJ, Kohnen PW, Gilbert DN. Influence of daptomycin on staphylococcal abscesses and experimental tobramycin nephrotoxicity. Antimicrob Agents Chemother. 1989 Aug;33(8):1280–1285. [PMC free article] [PubMed]
  • Wood CA, Kohlhepp SJ, Kohnen PW, Houghton DC, Gilbert DN. Vancomycin enhancement of experimental tobramycin nephrotoxicity. Antimicrob Agents Chemother. 1986 Jul;30(1):20–24. [PMC free article] [PubMed]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)