Proteomics analysis in the kidney of mice following oral feeding Realgar. (15th July 2021)

• Record Type: Journal Article
• Authors: Zhang, Sheng; Li, Chao; Feng, Tingting; Cao, Shuai; Zhou, Heng; Li, Liming; Hu, Qing; Mao, Xiuhong; Ji, Shen
• Is Part Of: Journal of ethnopharmacology. Volume 275(2021)
• Publication Date: 2021-07-15
• Subjects: Realgar -- Nephrotoxicity -- Label-free -- Proteomics -- Apoptosis -- Oxidative stress; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2021.114118
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Realgar, a famous traditional Chinese mineral medicine, has been toxic to the renal system. However, the underlying mechanism of Realgar nephrotoxicity is still unclear. Aim of the study: This study aimed to investigate the potential mechanism of Realgar-induced nephrotoxicity by using a label-free quantitative proteomic method. Materials and methods: 36 mice were randomly divided into four groups: Control group, 0.5-, 1.0, and 2.0 g/kg Realgar group. After one week, serum biochemical parameters and renal histopathological examination were performed. Label-free quantitative proteomics was used to identify differentially expressed proteins which were subsequently analyzed with bioinformatics methods. Western blot was utilized to verify the six representative protein expressions. Results: The results showed that 2.0 g/kg Realgar significantly increased blood urea nitrogen and induced the formation of tube cast of renal tubules, while the lower-dose of 0.5 g/kg and 1.0 g/kg Realgar showed no changes. Label-free proteomic analysis identified 3138 proteins, and 272 of those proteins were screened for significant changes in a dose-dependent manner. Functional enrichment analysis suggested that these proteins could affect the apoptotic process and oxidative stress. Representative proteins in the 2.0 g/kg Realgar group, including Cat, Bad, Cycs, Nqo1, Podxl, and Hmox1, were verified by western blot. Conclusions: The results in this study suggest that apoptosis and oxidative stress might be related to the Realgar-induced nephrotoxicity in mice. Moreover, the strategy of proteomics could contribute to the understanding of the mechanisms of nephrotoxicity in mice exposed to Realgar. Graphical abstract: Image 1 Highlights: Realgar damage to mice renal tubules. Proteomics analysis of Realgar-induced kidney toxicity in mice. Oxidative stress and apoptosis may be related to the Realgar-induced kidney injury.