title: A metabolic profiling analysis of the nephrotoxicity of acyclovir in rats using ultra performance liquid chromatography/mass spectrometry.
abstract: Acyclovir (ACV) exposure is a common cause of acute kidney injury (AKI). The toxicity mechanism of ACV has always been a matter of debate. The present study investigated into the time-effect relationship and dose-effect relationship of ACV-induced nephrotoxicity in rats using metabonomics. Twenty-four rats were randomly divided into four groups: a 0.9% NaCl solution group, and 100, 300, and 600mg/kg ACV-treated groups; the ACV or vehicle solution was administered with a single intravenous injection. Urine was collected at different time periods (12h before administration, and 0-6h, 7-12h, and 13-24h after administration). Routine urinalysis was conducted by a urine automatic analyzer. Renal markers, including urine urea nitrogen, urine creatinine, and urinary N-acetyl-β-d-glucosaminidase (NAG) activity, were determined using established protocols. Urinary metabolites were evaluated using ultra performance liquid chromatography/mass spectrometry (UPLC/MS). In the ACV-treated rats, increased levels of protein (PRO), occult blood (BLD), white blood cell (WBC), and NAG activity in urine were observed, while the urine creatinine and urea nitrogen levels showed a decrease compared with the control. Moreover, urine metabolites significantly changed after the treatment with ACV, and all the effects induced by ACV were dose-time dependent. Finally, 4 metabolites (guanine, 4-guanidinobutyric acid, creatinine, and urea) were identified, which can be used for further research on the mechanism of ACV-induced nephrotoxicity.
authors: Zhejiang Provincial Key Lab of Geriatrics and Geriatrics Institute of Zhejiang Province, Zhejiang Hospital, Hangzhou 310013, China.
authors: Wenmin
authors: W
authors: Xing
authors: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors: Lili
authors: L
authors: Gu
authors: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, China.
authors: Xinyue
authors: X
authors: Zhang
authors: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors: Jiadong
authors: J
authors: Xu
authors: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: luhong03@hotmail.com.
authors: Hong
authors: H
authors: Lu
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism* / Q000652:urine; D000212:Acyclovir / Q000633:toxicity*; D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D015415:Biomarkers / Q000652:urine; D004305:Dose-Response Relationship, Drug; D007677:Kidney Function Tests; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000212:Acyclovir
keywords: Acyclovir; Dose-time-effect relationship; Metabonomics; Nephrotoxicity