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Low cadmium exposure triggers a biphasic oxidative stress response in mice kidneys.
- Source :
-
Toxicology [Toxicology] 2007 Jul 01; Vol. 236 (1-2), pp. 29-41. Date of Electronic Publication: 2007 Mar 31. - Publication Year :
- 2007
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Abstract
- Oxidative stress is believed to participate in the early processes of cadmium (Cd)-induced proximal tubular kidney damage. Mice were chronically exposed up to 23 weeks to low Cd concentrations (10 and 100 mg CdCl(2)/l) via the drinking water. Pro- and antioxidant gene expression levels, glutathione, ascorbate and lipid peroxidation levels were measured. Our study provided evidence for an early and a late stress response in the kidney. Metallothioneins were upregulated from 1 week of exposure on and they stayed important during the whole exposure period. After 8 weeks the expression of Bcl2 (anti-apoptotic), Prdx2 and cytosolic superoxide dismutase (Sod1) was reduced in the group exposed to 100 mg CdCl(2)/l, which might indicate a response to Cd-stress. However glutathione, ascorbate and lipid peroxidation levels did not significantly change, and the overall redox balance remained stable. Stable Sod2 transcriptional levels suggested that an increased formation of superoxide anions, which can arise upon Cd-induced mitochondrial free radical generation, was not appearing. A second defence activation was observed after 23 weeks: i.e. an increase of catalase (Cat), glutathione peroxidase 4 (Gpx4) and heme oxygenase 1 (Hmox1), together with NADPH oxidase 4 (Nox4), of which the role has not been studied yet in Cd nephrotoxicity. These findings were in contrast with previous studies, where Cd-induced oxidative stress was detrimental when high Cd concentrations were applied. In conclusion our study provided evidence that a chronic exposure to low Cd concentrations triggered a biphasic defence activation in the kidney that might lead to adaptation and survival.
- Subjects :
- Animals
Ascorbic Acid metabolism
Catalase genetics
Gene Expression drug effects
Genes, bcl-2 drug effects
Glutathione metabolism
Glutathione Peroxidase genetics
Heme Oxygenase-1 genetics
Kidney metabolism
Lipid Peroxidation drug effects
Liver drug effects
Liver metabolism
Male
Metallothionein genetics
Metallothionein metabolism
Mice
Mice, Inbred C57BL
NADPH Oxidase 4
NADPH Oxidases genetics
Oxidative Stress genetics
RNA, Messenger metabolism
Reverse Transcriptase Polymerase Chain Reaction
Superoxide Dismutase genetics
Cadmium toxicity
Kidney drug effects
Oxidative Stress drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0300-483X
- Volume :
- 236
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Toxicology
- Publication Type :
- Academic Journal
- Accession number :
- 17499415
- Full Text :
- https://doi.org/10.1016/j.tox.2007.03.022