A metabolic profiling analysis of the nephrotoxicity of acyclovir in rats using ultra performance liquid chromatography/mass spectrometry

Publication date: Available online 28 July 2016 Source:Environmental Toxicology and Pharmacology Author(s): Wenmin Xing, Lili Gu, Xinyue Zhang, Jiadong Xu, Hong Lu 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 ind...
Source: Environmental Toxicology and Pharmacology - Category: Environmental Health Source Type: research