期刊
SCIENCE OF THE TOTAL ENVIRONMENT
卷 686, 期 -, 页码 1229-1237出版社
ELSEVIER
DOI: 10.1016/j.scitotenv.2019.04.409
关键词
Fluoride; Arsenite; Oxidative stress; Renal toxicity; Nrf2
资金
- National Natural Science Foundation of China [81872715, 81773405]
- China Postdoctoral Science Foundation [2016M600199]
- Program for the Outstanding Innovative Teams of Higher Learning Institutions of Shanxi
- Outstanding Youth Science Foundation of Shanxi Province [201701D211008]
- Shanxi Scholarship Council of China [2017-058]
- PhD Start-up Fund of Shanxi Medical University [BS03201647]
Underground drinking water is commonly contaminated with arsenite (As) and fluoride (F) associated with chronic kidney diseases in humans; however, the combined renal toxicity of these pollutants and the underlying mechanisms are still unclear. The aim of the present study was to investigate the interaction between As and F regarding toxic effects on the kidney of rat offspring exposed to pollutants during prenatal and postnatal development. Pregnant rats were randomly divided into four groups that received NaAsO2 (50 mg/L), NaF (100 mg/L), NaAsO2 (50 mg/L) and NaF (100 mg/L) in drinking water, or clean water, respectively, during gestation and lactation. After weaning, six male pups were randomly selected from each group and continued on the same treatment as their mothers for up to three months.The results revealed that subchronic exposure to high-dose As and/or F decreased the organ coefficient of the kidneys and disrupted kidney ultrastructure, moreover inhibited the activity of antioxidant enzymes and increased the generation of malondialdehyde in the kidney. As exposure alone or combined with F led to an upregulation of nuclear factor erythroid 2-related factor-2 (Nrf2) and its regulatory targets (Ho-1, Gclc, and Nqo1), whereas the effect of F alone was not significant. These results suggest that the renal toxicity of As and F is associated with the induction of mitochondrial damage and oxidative stress, and alters the expression of Nrf2 and its regulatory targets. Furthermore, variance analysis results showed that an interaction between As and F in the toxicity process. (C) 2019 Elsevier B.V. All rights reserved.
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