title: Plasma metabolic profiling analysis of nephrotoxicity induced by acyclovir using metabonomics coupled with multivariate data analysis.
abstract: Acyclovir (ACV) is an antiviral agent. However, its use is limited by adverse side effect, particularly by its nephrotoxicity. Metabonomics technology can provide essential information on the metabolic profiles of biofluids and organs upon drug administration. Therefore, in this study, mass spectrometry-based metabonomics coupled with multivariate data analysis was used to identify the plasma metabolites and metabolic pathways related to nephrotoxicity caused by intraperitoneal injection of low (50mg/kg) and high (100mg/kg) doses of acyclovir. Sixteen biomarkers were identified by metabonomics and nephrotoxicity results revealed the dose-dependent effect of acyclovir on kidney tissues. The present study showed that the top four metabolic pathways interrupted by acyclovir included the metabolisms of arachidonic acid, tryptophan, arginine and proline, and glycerophospholipid. This research proves the established metabonomic approach can provide information on changes in metabolites and metabolic pathways, which can be applied to in-depth research on the mechanism of acyclovir-induced kidney injury.
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors.forename: Xiuxiu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors.forename: Yubo
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Experimental Teaching, Tianjin University of Traditional Chinese Medicine, 88 Yuquan Road, Tianjin 300193, China.
authors.forename: Huifang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors.forename: Simiao
authors.initials: S
authors.lastname: Fan
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors.forename: Zhenzhu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China. Electronic address: tianjin_tcm001@sina.com.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000212:Acyclovir / Q000009:adverse effects*; D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods*; D015999:Multivariate Analysis; D010949:Plasma / Q000378:metabolism*; D051381:Rats
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000212:Acyclovir
keywords: Acyclovir; Metabonomics; Multivariate data analysis; Nephrotoxicity; RRLC-Q-TOF-MS