Hydroxyl radical formation and lipid peroxidation enhancement by chromium

Chromium VI compounds have been shown to be carcinogenic in occupationally exposed humans, and to be genotoxic, mutagenic, and carcinogenic in a variety of experimental systems. In contrast, most chromium III compounds are relatively nontoxic, noncarcinogenic, and nonmutagenic. Reduction of Cr⁶⁺ leads to reactive intermediates, such as Cr⁵⁺, Cr⁴⁺, or other radical species. The molecular mechanism for the intracellular Cr⁶⁺ reduction has been the focus of recent studies, but the details are still not understood. Our study was initiated to compare the effect of Cr⁶⁺-hydroxyl radical formation and Cr⁶⁺-induced lipid peroxidation vs those of Cr³⁺. Electron spin responance measurements provide evidence for the formation of long-lived Cr⁵⁺ intermediates in the reduction of Cr⁶⁺ by glutathione reductase in the presence of NADPH and for the hydroxyl radical formation during the glutathione reductase catalyzed reduction of Cr⁶⁺. Hydrogen peroxide suppresses Cr⁵⁺ and enhances the formation of hydroxyl radical. Thus, Cr⁵⁺ intermediates catalyze generation of hydroxyl radicals from hydrogen peroxide through a Fenton-like reaction. Comparative effects of Cr⁶⁺ and Cr³⁺ on the development of lipid peroxidation were studied by using rat heart homogenate. Heart homogenate was incubated with different concentrations of Cr⁶⁺ compounds at 22°C for 60 min. Lipid peroxidation was determined as thiobarbituric acid reacting materiels (TBA-RM). The results confirm that Cr⁶⁺ induces lipid peroxidation in the rat heart homogenate. These observations might suggest a possible causative role of lipid peroxidation in Cr⁶⁺ toxicity. This enhancement of lipid peroxidation is modified by the addition of some metal chelators and antioxidants. Thus, strategies for combating Cr⁶⁺ toxicity should take into account the role of the hydroxy radicals, and hence, steps for blocking its chain propagation and preventing the formation of lipid peroxides.