Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1996 Mar;40(3):802–806. doi: 10.1128/aac.40.3.802

Temporal variation in nephrotoxicity of low doses of isepamicin in rats.

Y Yoshiyama 1, L Grenier 1, P Gourde 1, M Simard 1, L Lin 1, N J Morin 1, M G Bergeron 1, G Labrecque 1, D Beauchamp 1
PMCID: PMC163205  PMID: 8851618

Abstract

The temporal variation in the nephrotoxicity of low doses of isepamicin was studied in male Sprague-Dawley rats treated with a single daily intraperitoneal injection of saline (NaCl, 0.9%) or isepamicin (80 mg/kg of body weight) at either 0800, 1400, 2000, or 0200 h for 4 and 10 days. On day 10, the cellular regeneration (incorporation of [3H] thymidine into DNA of renal cortex) and cortical accumulation of isepamicin were significantly higher in animals treated at 1400 h than at 0200 h (P < 0.01). Immunogold labeling studies showed that isepamicin was essentially localized in the lysosomes of proximal tubular cells in all treated groups, but the density of the gold particles over the lysosomes was higher in animals treated at 1400 than at 0200 h. The results of the present study show that the renal toxicity of isepamicin was maximal at 1400 h (midlight period) and minimal at 0200 h (middark period).

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bates R. D., Nahata M. C. Once-daily administration of aminoglycosides. Ann Pharmacother. 1994 Jun;28(6):757–766. doi: 10.1177/106002809402800614. [DOI] [PubMed] [Google Scholar]
  2. Beauchamp D., Gourde P., Bergeron M. G. Subcellular distribution of gentamicin in proximal tubular cells, determined by immunogold labeling. Antimicrob Agents Chemother. 1991 Nov;35(11):2173–2179. doi: 10.1128/aac.35.11.2173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beauchamp D., Laurent G., Maldague P., Abid S., Kishore B. K., Tulkens P. M. Protection against gentamicin-induced early renal alterations (phospholipidosis and increased DNA synthesis) by coadministration of poly-L-aspartic acid. J Pharmacol Exp Ther. 1990 Nov;255(2):858–866. [PubMed] [Google Scholar]
  4. Beauchamp D., Pellerin M., Gourde P., Pettigrew M., Bergeron M. G. Effects of daptomycin and vancomycin on tobramycin nephrotoxicity in rats. Antimicrob Agents Chemother. 1990 Jan;34(1):139–147. doi: 10.1128/aac.34.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bendayan M., Zollinger M. Ultrastructural localization of antigenic sites on osmium-fixed tissues applying the protein A-gold technique. J Histochem Cytochem. 1983 Jan;31(1):101–109. doi: 10.1177/31.1.6187796. [DOI] [PubMed] [Google Scholar]
  6. Bennett W. M., Elliott W. C., Houghton D. C., Gilbert D. N., DeFehr J., McCarron D. A. Reduction of experimental gentamicin nephrotoxicity in rats by dietary calcium loading. Antimicrob Agents Chemother. 1982 Sep;22(3):508–512. doi: 10.1128/aac.22.3.508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bennett W. M., Plamp C. E., Gilbert D. N., Parker R. A., Porter G. A. The influence of dosage regimen on experimental gentamicin nephrotoxicity: dissociation of peak serum levels from renal failure. J Infect Dis. 1979 Oct;140(4):576–580. doi: 10.1093/infdis/140.4.576. [DOI] [PubMed] [Google Scholar]
  8. Dorian C., Catroux P., Cambar J. Etude de la chrononéphrotoxicité de l'amikacine après intoxication chronique de sept jours chez le rat. Pathol Biol (Paris) 1987 Jun;35(5 Pt 2):735–738. [PubMed] [Google Scholar]
  9. Fantin B., Pangon B., Potel G., Vallois J. M., Caron F., Bure A., Carbon C. Ceftriaxone-netilmicin combination in single-daily-dose treatment of experimental Escherichia coli endocarditis. Antimicrob Agents Chemother. 1989 May;33(5):767–770. doi: 10.1128/aac.33.5.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Francioli P. B., Glauser M. P. Synergistic activity of ceftriaxone combined with netilmicin administered once daily for treatment of experimental streptococcal endocarditis. Antimicrob Agents Chemother. 1993 Feb;37(2):207–212. doi: 10.1128/aac.37.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fujimura A., Sudoh T., Ebihara A. Time-dependent change in the toxic effects of amikacin on renal functions. Life Sci. 1994;55(5):367–372. doi: 10.1016/0024-3205(94)00647-4. [DOI] [PubMed] [Google Scholar]
  12. Gilbert D. N., Wood C. A., Kohlhepp S. J., Kohnen P. W., Houghton D. C., Finkbeiner H. C., Lindsley J., Bennett W. M. Polyaspartic acid prevents experimental aminoglycoside nephrotoxicity. J Infect Dis. 1989 May;159(5):945–953. doi: 10.1093/infdis/159.5.945. [DOI] [PubMed] [Google Scholar]
  13. Hosokawa H., Nyu S., Nakamura K., Mifune K., Nakano S. Circadian variation in amikacin clearance and its effects on efficacy and toxicity in mice with and without immunosuppression. Chronobiol Int. 1993 Aug;10(4):259–270. doi: 10.1080/07420529309059708. [DOI] [PubMed] [Google Scholar]
  14. Humes H. D., Sastrasinh M., Weinberg J. M. Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity. J Clin Invest. 1984 Jan;73(1):134–147. doi: 10.1172/JCI111184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kabins S. A., Nathan C. In vitro activity of Sch 21420, derivative of gentamicin B, compared to that of amikacin. Antimicrob Agents Chemother. 1978 Nov;14(5):786–787. doi: 10.1128/aac.14.5.786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kacew S. Inhibition of gentamicin-induced nephrotoxicity by pyridoxal-5'-phosphate in the rat. J Pharmacol Exp Ther. 1989 Jan;248(1):360–366. [PubMed] [Google Scholar]
  17. Laurent G., Maldague P., Carlier M. B., Tulkens P. M. Increased renal DNA synthesis in vivo after administration of low doses of gentamicin to rats. Antimicrob Agents Chemother. 1983 Oct;24(4):586–593. doi: 10.1128/aac.24.4.586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lee S. M., Michael U. F. The protective effect of nitrendipine on gentamicin acute renal failure in rats. Exp Mol Pathol. 1985 Aug;43(1):107–114. doi: 10.1016/0014-4800(85)90060-7. [DOI] [PubMed] [Google Scholar]
  19. Lin L., Grenier L., Bergeron Y., Simard M., Bergeron M. G., Labrecque G., Beauchamp D. Temporal changes of pharmacokinetics, nephrotoxicity, and subcellular distribution of tobramycin in rats. Antimicrob Agents Chemother. 1994 Jan;38(1):54–60. doi: 10.1128/aac.38.1.54. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lin L., Grenier L., Thériault G., Gourde P., Yoshiyama Y., Bergeron M. G., Labrecque G., Beauchamp D. Nephrotoxicity of low doses of tobramycin in rats: effect of the time of administration. Life Sci. 1994;55(3):169–177. doi: 10.1016/0024-3205(94)00877-9. [DOI] [PubMed] [Google Scholar]
  21. Lucht F., Tigaud S., Esposito G., Cougnard J., Fargier M. P., Peyramond D., Bertrand J. L. Chronokinetic study of netilmicin in man. Eur J Clin Pharmacol. 1990;39(2):199–201. doi: 10.1007/BF00280062. [DOI] [PubMed] [Google Scholar]
  22. Matsumoto T., Kumazawa J., Ueda S., Eto K., Yushita Y., Saito Y., Ishii T., Sawae Y. Treatment of complicated urinary tract infections with ofloxacin following an aminoglycoside. Chemotherapy. 1991;37 (Suppl 1):60–67. doi: 10.1159/000238908. [DOI] [PubMed] [Google Scholar]
  23. Minguez F., Agra M., Lurueña S., Ramos C., Prieto J. Post-antibiotic effect of isepamicin compared to that of other aminoglycosides. Drugs Exp Clin Res. 1990;16(5):231–235. [PubMed] [Google Scholar]
  24. Pariat C., Courtois P., Cambar J., Piriou A., Bouquet S. Circadian variations in the renal toxicity of gentamicin in rats. Toxicol Lett. 1988 Feb;40(2):175–182. doi: 10.1016/0378-4274(88)90159-2. [DOI] [PubMed] [Google Scholar]
  25. Potel G., Chau N. P., Pangon B., Fantin B., Vallois J. M., Faurisson F., Carbon C. Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding. Antimicrob Agents Chemother. 1991 Oct;35(10):2085–2090. doi: 10.1128/aac.35.10.2085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Powell S. H., Thompson W. L., Luthe M. A., Stern R. C., Grossniklaus D. A., Bloxham D. D., Groden D. L., Jacobs M. R., DiScenna A. O., Cash H. A. Once-daily vs. continuous aminoglycoside dosing: efficacy and toxicity in animal and clinical studies of gentamicin, netilmicin, and tobramycin. J Infect Dis. 1983 May;147(5):918–932. doi: 10.1093/infdis/147.5.918. [DOI] [PubMed] [Google Scholar]
  27. Rankin L. I., Luft F. C., Yum M. N., Sloan R. S., Dinwiddie C. B., Jr, Isaacs L. L. Comparative nephrotoxicity of SCH 21420 and amikacin in rats. Antimicrob Agents Chemother. 1979 Oct;16(4):491–494. doi: 10.1128/aac.16.4.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sanders C. C., Sanders W. E., Jr, Goering R. V. In vitro studies with Sch 21420 and Sch 22591: activity in comparison with six other aminoglycosides and synergy with penicillin against enterococci. Antimicrob Agents Chemother. 1978 Aug;14(2):178–184. doi: 10.1128/aac.14.2.178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Song J., Ohdo S., Ogawa N., Nakano S. Influence of feeding schedule on chronopharmacological aspects of gentamicin in mice. Chronobiol Int. 1993 Oct;10(5):338–348. doi: 10.3109/07420529309064488. [DOI] [PubMed] [Google Scholar]
  30. Suzuki K., Horiba M., Nagata Y. [Pharmacokinetic and clinical studies on isepamicin in chronic complicated urinary tract infection using daily single dose treatment]. Jpn J Antibiot. 1990 Sep;43(9):1649–1659. [PubMed] [Google Scholar]
  31. Takumida M., Nishida I., Nikaido M., Hirakawa K., Harada Y., Bagger-Sjöbäck D. Effect of dosing schedule on aminoglycoside ototoxicity: comparative cochlear ototoxicity of amikacin and isepamicin. ORL J Otorhinolaryngol Relat Spec. 1990;52(6):341–349. doi: 10.1159/000276162. [DOI] [PubMed] [Google Scholar]
  32. Vaught J. L., Carson J. R., Carmosin R. J., Blum P. S., Persico F. J., Hageman W. E., Shank R. P., Raffa R. B. Antinociceptive action of McN-5195 in rodents: a structurally novel (indolizine) analgesic with a nonopioid mechanism of action. J Pharmacol Exp Ther. 1990 Oct;255(1):1–10. [PubMed] [Google Scholar]
  33. Wood C. A., Finkbeiner H. C., Kohlhepp S. J., Kohnen P. W., Gilbert D. N. Influence of daptomycin on staphylococcal abscesses and experimental tobramycin nephrotoxicity. Antimicrob Agents Chemother. 1989 Aug;33(8):1280–1285. doi: 10.1128/aac.33.8.1280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yoshiyama Y., Kobayashi T., Tomonaga F., Nakano S. Chronotoxical study of gentamicin induced nephrotoxicity in rats. J Antibiot (Tokyo) 1992 May;45(5):806–808. doi: 10.7164/antibiotics.45.806. [DOI] [PubMed] [Google Scholar]
  35. Yoshiyama Y., Nishikawa S., Sugiyama T., Kobayashi T., Shimada H., Tomonaga F., Ohdo S., Ogawa N., Nakano S. Influence of circadian-stage-dependent dosing schedule on nephrotoxicity and pharmacokinetics of isepamicin in rats. Antimicrob Agents Chemother. 1993 Sep;37(9):2042–2043. doi: 10.1128/aac.37.9.2042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yu P. K., Washington J. A., 2nd In vitro evaluation of a semisynthetic derivative of gentamicin B (Sch 21420). Antimicrob Agents Chemother. 1978 May;13(5):891–892. doi: 10.1128/aac.13.5.891. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES