title: Hydroxyl radical formation and lipid peroxidation enhancement by chromium. In vitro study.
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 Cr(6+)-hydroxyl radical formation and Cr(6+)-induced lipid peroxidation vs those of Cr3+. Electron spin resonance 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 degrees 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.
authors.affiliation: Laboratoire de Biochimie C, Centre Hospitalier Régional de Grenoble, France.
authors.forename: C
authors.initials: C
authors.lastname: Coudray
authors.forename: P
authors.initials: P
authors.lastname: Faure
authors.forename: S
authors.initials: S
authors.lastname: Rachidi
authors.forename: A
authors.initials: A
authors.lastname: Jeunet
authors.forename: M J
authors.initials: MJ
authors.lastname: Richard
authors.forename: A M
authors.initials: AM
authors.lastname: Roussel
authors.forename: A
authors.initials: A
authors.lastname: Favier
mesh_terms: D000818:Animals; D002857:Chromium / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D005980:Glutathione Reductase / Q000378:metabolism / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009249:NADP / Q000378:metabolism / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D006878:Hydroxides; D002857:Chromium; D017665:Hydroxyl Radical; D009249:NADP; D006861:Hydrogen Peroxide; D005980:Glutathione Reductase