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Biol Pharm Bull. 2017;40(7):975-983. doi: 10.1248/bpb.b16-00932.

Time-Dependent Alterations of Vancomycin-Induced Nephrotoxicity in Mice.

Author information

1
Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology.
2
Department of Pharmacy, Tokyo Metropolitan Geriatric Hospital.
3
Department of Nephrology, Tokyo Metropolitan Geriatric Hospital.
4
Department of Pathology, Tokyo Metropolitan Geriatric Hospital.
5
Department of Pharmacy, Pusan National University.
6
Department of Practical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University.

Abstract

Vancomycin hydrochloride (VCM) is a glycopeptide antibiotic that is commonly used against methicillin-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 400 mg/kg body weight at 24-h intervals for 3, 5, 7, and 14 d. At 24 h 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.

KEYWORDS:

CD10; apoptosis; kidney; nephrotoxicity; vancomycin

PMID:
28674262
DOI:
10.1248/bpb.b16-00932
[Indexed for MEDLINE]
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