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J Nutr Sci Vitaminol (Tokyo). 2019;65(5):399-404. doi: 10.3177/jnsv.65.399.

High-Dose Vitamin C Preadministration Reduces Vancomycin-Associated 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 Anesthesiology, Oita University Faculty of Medicine.
4
College of Pharmacy, Pusan National University.
5
Department of Pathology, Tokyo Metropolitan Geriatric Hospital.
6
Department of Practical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University.

Abstract

Vancomycin is recommended for treating severe infections caused by Gram-positive cocci, including methicillin-resistant Staphylococcus aureus. However, renal damage often occurs as a side effect because vancomycin is mainly excreted via the kidneys. The mechanism of vancomycin-associated nephrotoxicity is thought to involve the elevation of oxidative stress in the kidneys. Vitamin C (VC) has strong antioxidant properties; therefore, we evaluated the effect of high-dose VC preadministration on vancomycin-associated nephrotoxicity. Vancomycin was intraperitoneally injected into mice once daily for 7 d. Additionally, high-dose VC was intraperitoneally injected into mice at 30 min before vancomycin administration for 7 d. The plasma creatinine and urea nitrogen levels were increased by vancomycin treatment; however, high-dose VC preadministration suppressed the increase in these levels. Histological examination also revealed that high-dose VC preadministration reduced the characteristics of vancomycin-associated nephrotoxicity, such as dilated renal tubules with casts, the dilation of renal proximal tubules, and tubular epithelial desquamation. Furthermore, high-dose VC preadministration reduced the appearance of apoptotic cells presumably derived from the epithelial cells in the dilated proximal tubules. Thus, intraperitoneally injected high-dose VC preadministration reduced vancomycin-associated nephrotoxicity in mice. These novel findings may indicate that vancomycin-associated nephrotoxicity in humans may be reduced by high-dose VC preadministration.

KEYWORDS:

CD10; ascorbic acid; creatinine; kidney; nephrotoxicity; urine; vancomycin; vitamin C

PMID:
31666476
DOI:
10.3177/jnsv.65.399
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