title: Safety of trivalent chromium complexes: no evidence for DNA damage in human HaCaT keratinocytes.
abstract: Several studies have demonstrated beneficial effects of supplemental trivalent Cr in subjects with reduced insulin sensitivity with no documented signs of toxicity. However, recent studies have questioned the safety of supplemental trivalent Cr complexes. The objective of this study was to evaluate the cytotoxic and genotoxic potential of the Cr(III) complexes (histidinate, picolinate, and chloride) used as nutrient supplements compared with Cr(VI) dichromate. The cytotoxic and genotoxic effects of the Cr complexes were assessed in human HaCaT keratinocytes. The concentrations of Cr required to decrease cell viability were assessed by determining the ability of a keratinocyte cell line (HaCaT) to reduce tetrazolium dye, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. DNA damage using the Comet assay and the production of 8-hydroxy-2'-deoxyguanosine were also determined with and without hydrogen peroxide-induced stress. The LC50 for human cultured HaCaT keratinocytes was 50 microM for hexavalent sodium dichromate and more than 120-fold higher for Cr chloride (6 mM) and Cr histidinate (10 mM). For Cr picolinate at saturating concentration (120 microM) the LC50 was not attained. High Cr(III) concentrations, 250 microM Cr as Cr chloride and Cr histidinate and 120 microM Cr picolinate (highest amount soluble in the system), not only did not result in oxidative DNA damage but exhibited protective antioxidant effects when cells were exposed to hydrogen peroxide-induced oxidative stress. These data further support the low toxicity of trivalent Cr complexes used in nutrient supplements.
authors.affiliation: Laboratoire Nutrition, Vieillissement, Maladies Cardiovasculaires, EA 3746, J. Fourier University, Domaine de la Merci, 38700 La Tronche, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Hininger
authors.forename: Rachida
authors.initials: R
authors.lastname: Benaraba
authors.forename: Mireille
authors.initials: M
authors.lastname: Osman
authors.forename: Henri
authors.initials: H
authors.lastname: Faure
authors.forename: Anne
authors.initials: A
authors.lastname: Marie Roussel
authors.forename: Richard A
authors.initials: RA
authors.lastname: Anderson
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D002274:Carcinogens, Environmental / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D002840:Chromates / Q000494:pharmacology; D002857:Chromium / Q000737:chemistry*; D017608:Chromium Compounds / Q000494:pharmacology*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D019587:Dietary Supplements; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D010084:Oxidation-Reduction; D010848:Picolinic Acids / Q000494:pharmacology
chemical_list: D002274:Carcinogens, Environmental; D002712:Chlorides; D002840:Chromates; D017608:Chromium Compounds; D016877:Oxidants; D010848:Picolinic Acids; D002857:Chromium; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; C016104:sodium bichromate; D007770:L-Lactate Dehydrogenase; D003849:Deoxyguanosine; C030614:picolinic acid