Glutathione-mediated protection against chromium-induced dermal toxicity.
Joseph P; Noore J; Umbright C
Toxicologist 2007 Mar; 96(1):431
Occupational exposure to compounds containing chromium has been identified as a risk factor for developing irritant and contact dermatitis among workers. Induction of oxidative stress has been implicated as one of the major mechanisms responsible for the toxicity and the adverse health effects due to exposure to chromium. Presently, we have studied the role of glutathione in the toxicity of chromium following its dermal exposure in mice. The tissue glutathione levels of C57BL/6 mice were depleted by providing them with drinking water containing 20 mM buthionine sulfoximine (BSO). Hexavalent chromium (K2Cr2O7) was applied on the skin of control and BSO-fed mice on alternate days at doses of 0, 1, 5 and 10 mg/kg b.w. either for 2 or 4 weeks. The chromium-induced lesions noticed on the skin of the mice correlated with the dose and duration of the chemical application. In general, the animals with depleted tissue levels of glutathione exhibited more severe skin lesions compared with the control animals indicating the enhanced susceptibility of the GSH-depleted mice to chromium-induced dermal toxicity. Similarly, the amounts of 8-hydroxydeoxy guanosine (8-OHdG) and malondialdehyde (MDA)-indicators of oxidative damage to tissue DNA and lipids, respectively, were higher in the skin of the GSH-depleted mice treated with chromium compared with the controls. The enhanced dermal toxicity of chromium noticed among the GSH-depleted mice compared with the corresponding controls was further supported by the results of gene expression and histopathology studies. In conclusion, these results suggest that the tissue level of glutathione is an important determining factor in the response of mice to the dermal toxicity induced by hexavalent chromium.
Toxic-effects; Cytotoxic-effects; Cytotoxins; Cytotoxicity; Cellular-reactions; Animal-studies; Toxicopathology; Oxidative-processes; Skin-disorders; Skin-exposure; Skin-infections; Skin-irritants; Skin-sensitivity; Dermatitis; Histopathology; Histochemical-analysis; Histology; Genotoxicity; Genes
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina