Journal article
Nrf2 deficiency aggravates the kidney injury induced by subacute cadmium exposure in mice
Archives of toxicology, Vol.95(3), pp.883-893
03/01/2021
DOI: 10.1007/s00204-020-02964-3
PMID: 33398418
Abstract
Cadmium (Cd) is a heavy metal pollutant that adversely effects the kidney. Oxidative stress and inflammation are likely major mechanisms of Cd-induced kidney injury. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is crucial in regulating antioxidant and inflammatory responses. To investigate the role of Nrf2 in the development of subacute Cd-induced renal injury, we utilized Nrf2 knockout (Nrf2-KO) and control mice (Nrf2-WT) which were given cadmium chloride (CdCl2, 1 or 2 mg/kg i.p.) once daily for 7 days. While subacute CdCl2 exposure induced kidney injury in a dose-dependent manner, after the higher Cd dosage exposure, Nrf2-KO mice showed elevated blood urea nitrogen (BUN) and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels compared to control. In line with the findings, the renal tubule injury caused by 2 mg Cd/kg, but not lower dosage, in Nrf2-KO mice determined by Periodic acid-Schiff staining was more serious than that in control mice. Further mechanistic studies showed that Nrf2-KO mice had more apoptotic cells and severe oxidative stress and inflammation in the renal tubules in response to Cd exposures. Although there were no significant differences in Cd contents of tissues between Cd-exposed Nrf2-WT and Nrf2-KO mice, the mRNA expression of Nrf2 downstream genes, including heme oxygenase 1 and metallothionein 1, were significantly less induced by Cd exposures in the kidney of Nrf2-KO compared with Nrf2-WT mice. In conclusion, Nrf2-deficient mice are more sensitive to kidney injury induced by subacute Cd exposure due to a muted antioxidant response, as well as a likely diminished production of specific Cd detoxification metallothioneins.
Details
- Title: Subtitle
- Nrf2 deficiency aggravates the kidney injury induced by subacute cadmium exposure in mice
- Creators
- Chengjie Chen - China Medical UniversityXue Han - China Medical UniversityGang Wang - Experimental and Teaching Center, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People's Republic of China.Dan Liu - China Medical UniversityLina Bao - China Medical UniversityCongcong Jiao - China Medical UniversityJunjun Luan - China Medical UniversityYongyong Hou - China Medical UniversityYuanyuan Xu - China Medical UniversityHuihui Wang - China Medical UniversityQiang Zhang - Emory UniversityHua Zhou - China Medical UniversityJingqi Fu - China Medical UniversityJingbo Pi - China Medical University
- Resource Type
- Journal article
- Publication Details
- Archives of toxicology, Vol.95(3), pp.883-893
- Publisher
- Springer Nature
- DOI
- 10.1007/s00204-020-02964-3
- PMID
- 33398418
- ISSN
- 0340-5761
- eISSN
- 1432-0738
- Number of pages
- 11
- Grant note
- Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic 2019JH8/10300012 / Liaoning Key Research and Development Guidance Plan ZF2019035 / Educational Department of Liaoning Province Scientific Research Foundation 20180530011 / Liaoning Province Natural Science Foundation; Natural Science Foundation of Liaoning Province YQ20170001 / China Medical University Training Program for National Natural Science Fund for Excellent Young Scholars 82020108027; 81830099; 81573106; 81770698; 81402635 / National Natural Science Foundation of China; National Natural Science Foundation of China (NSFC)
- Language
- English
- Date published
- 03/01/2021
- Academic Unit
- Neurology
- Record Identifier
- 9984302214002771
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