Exposing mice to low Cd doses triggers a biphasic oxidative stress response in the kidney: a role for Prdx2 and Nox4?

Abstract

In previous studies exposing animals to Cd caused oxidative stress and kidney damage. Mostly high doses were applied, often by injection. In the present study mice were exposed up to 23 weeks to low Cd concentrations (10 and 100 mg CdCl2/l) in the drinking water.

Antioxidant gene expression levels as well as glutathione, ascorbate and lipid peroxidation levels were measured.

Metallothionein 1 and 2 were upregulated from 1 week of exposure on. An early induction of the Prdx2 gene suggested that peroxiredoxin might be involved in the early response as well.

After 8 weeks Cd reduced antioxidant expression of Bcl2, Prdx2 and Sod1 which might indicate a toxic effect. No significant effect was seen on lipid peroxidation however, and the overall redox status remained in balance throughout the whole experiment. Levels of reduced glutathione and ascorbate and of transcription of Sod2 remained stable. This suggested that the energy maintenance in mitochondria was under control.

A second response was observed after 23 weeks. Interestingly, the expression of renal NADPH oxidase 4 (Nox4) increased. Nox4 has not been studied yet in Cd nephrotoxicity. The antioxidants catalase, glutathione peroxidase 4 and heme oxygenase 1 also responded. In conclusion our study reveals a two-step oxidative stress response in the kidney. Clearly the kidney was in control of Cd-induced oxidative stress after exposure to low Cd concentrations.