Time-dependent alterations of vancomycin-induced nephrotoxicity in mice

Masaki Takigawa, Hirofumi Masutomi, Yuki Kishimoto, Yoshitomo Shimazaki, Yoshitomo Hamano, Yoshitaka Kondo, Tomio Arai, Jaewon Lee, Toshihiro Ishii, Yoshiko Mori, Akihito Ishigami

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic that is commonly used against methicil-lin-resistant, Gram-positive cocci despite the nephrotoxic side effects. VCM-induced nephrotoxicity has been reported in 5–28% of recipient patients. Therefore, renal failure induced by VCM has become an important clinical problem. However, the exceedingly complex mechanism of VCM-induced nephrotoxicity is not fully understood. Therefore, this study was designed to clarify time-dependent alterations of VCM-induced nephrotoxicity in mice as a step toward decreasing the risks of kidney injury associated with VCM therapy. VCM was injected intraperitoneally into mice at a dose of 400mg/kg body weight at 24-h intervals for 3, 5, 7, and 14d. At 24h after the last injection, we examined histopathological alterations of the kidney as well as blood biochemistry. VCM administration resulted in a decrease of body weight and increase of kidney weight. Histological examination revealed renal damage such as dilated proximal tubules with occasional casts and interstitial fibrosis in VCM-treated mice. Furthermore, immunohistochemical staining with anti-CD10 and anti-single-stranded DNA antibodies highlighted damaged renal proximal tubules with marked dilatation as well as numerous apoptotic cells as early as day 4 of VCM-treatment. The severity of symptoms progressed until day 15. These results suggest that VCM-induced renal damage and incipient renal failure begin soon after the start of treatment and progressively worsen. This is the first report describing the time-dependence of VCM-induced nephrotoxicity in mice and depicting a model that clarifies the mechanisms of this tissue damage.

Original languageEnglish
Pages (from-to)975-983
Number of pages9
JournalBiological and Pharmaceutical Bulletin
Volume40
Issue number7
DOIs
Publication statusPublished - 2017
Externally publishedYes

Keywords

  • Apoptosis
  • CD10
  • Kidney
  • Nephrotoxicity
  • Vancomycin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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  • Cite this

    Takigawa, M., Masutomi, H., Kishimoto, Y., Shimazaki, Y., Hamano, Y., Kondo, Y., Arai, T., Lee, J., Ishii, T., Mori, Y., & Ishigami, A. (2017). Time-dependent alterations of vancomycin-induced nephrotoxicity in mice. Biological and Pharmaceutical Bulletin, 40(7), 975-983. https://doi.org/10.1248/bpb.b16-00932