Low cadmium exposure triggers a biphasic oxidative stress response in mice kidneys

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• 作者：S ; y Thijssen ; Ann Cuypers ; John Maringwa ; Karen Smeets ; Nele Horemans ; Ivo Lambrichts ; Emmy Van Kerkhove
• 关键词：Antioxidants ; Cadmium ; Chronic low-level exposure ; Gene expression ; Kidney ; Stress response
• 刊名：Toxicology
• 出版年：2007
• 出版时间：1 July 2007
• 年：2007
• 卷：236
• 期：1-2
• 页码：29-41
• 全文大小：1079 K

文摘

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 CdCl₂/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 CdCl₂/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.