title: Proteomic characterization of acyclovir-induced nephrotoxicity in a mouse model.
abstract: Acyclovir (ACV) is an effective and widely used antiviral agent. However, its clinical application is limited by severe nephrotoxicity. We assessed ACV-induced nephrotoxicity and identified the differentially expressed proteins using mass spectrometry-based proteomic analysis. In total, 30 ICR mice were intraperitoneally administrated ACV (150 or 600 mg/kg per day) for 9 days. After administration of ACV, levels of serum creatinine and urea nitrogen increased significantly. In addition, mouse kidneys exhibited histopathological changes and reduced expression levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR2. In the proteomic analysis, more than 1,000 proteins were separated by two-dimensional polyacrylamide gel electrophoresis, and a total of 20 proteins were up- or down-regulated in the ACV group compared with the saline group. Among these, six proteins (MHC class II antigen, glyoxalase 1, peroxiredoxin 1, αB-crystallin, fibroblast growth factor receptor 1-IIIb, and cytochrome c oxidase subunit Vb) were identified in association with ACV-induced nephrotoxicity. These findings were confirmed by Western blotting analysis. The differential expression levels of α-BC, Prx1, Glo I and CcO Vb suggest that oxidative damage and mitochondrial injury may be involved in ACV-induced nephrotoxicity. Furthermore, VEGF and FGF may play a role in tissue repair and the restoration process following ACV nephrotoxicity.
authors: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors: Hong
authors: H
authors: Lu
authors: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors: Ya-Juan
authors: YJ
authors: Han
authors: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors: Jia-Dong
authors: JD
authors: Xu
authors: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors: Wen-Min
authors: WM
authors: Xing
authors: School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou, PR China.
authors: Jie
authors: J
authors: Chen
mesh_terms: D000212:Acyclovir / Q000633:toxicity*; D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D051379:Mice; D008813:Mice, Inbred ICR; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D040901:Proteomics; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
chemical_list: D000998:Antiviral Agents; D020543:Proteome; D042461:Vascular Endothelial Growth Factor A; D003404:Creatinine; D040301:Vascular Endothelial Growth Factor Receptor-2; D000212:Acyclovir