Abstract
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.
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Abbreviations
- Cr:
-
chromium
- Desferal:
-
Deferoxamine
- DMPO:
-
5,5′-dimethyl-1-pyroline-N-oxide
- DMSO:
-
Dimethyl sulfoxide
- EDTA:
-
ethylenediaminetetraacetic acid
- ESR:
-
electron spin resonance
- GRx:
-
glutathione reductase
- H2O2 :
-
hydrogen peroxide
- NADPH:
-
β-nicotinamide adenine dinucleotide phosphate, reduced form
- OH:
-
hydroxyl radical
- TBA-RM:
-
thiobarbituric acid reacting materials
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Coudray, C., Faure, P., Rachidi, S. et al. Hydroxyl radical formation and lipid peroxidation enhancement by chromium. Biol Trace Elem Res 32, 161–170 (1992). https://doi.org/10.1007/BF02784601
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DOI: https://doi.org/10.1007/BF02784601