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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.

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Molecular Regulation of Aging, Tokyo Metropolitan Institute of Gerontology.
Department of Pharmacy, Tokyo Metropolitan Geriatric Hospital.
Department of Anesthesiology, Oita University Faculty of Medicine.
College of Pharmacy, Pusan National University.
Department of Pathology, Tokyo Metropolitan Geriatric Hospital.
Department of Practical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University.


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.


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

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