Publications (38) View all
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Article: Laboratory studies of the impact of calcite on in vitro and in vivo effects of coal dust: A potential preventive agent for coal workers' pneumoconiosis?
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ABSTRACT: BACKGROUND: Bioavailable iron (BAI) in coal, which may play a key role in causing coal workers' pneumoconiosis (CWP), is present at relatively high levels in Appalachian coals. Calcite decreases BAI and is more plentiful in Western coals than in Appalachian coals, possibly explaining the lower CWP prevalence among Western miners. METHODS: We measured effects of calcite on BAI in non-cellular and cellular systems involving Pennsylvania (PA) coal dust. We also tested in vivo effects of calcite on transferrin receptor and markers of epithelial mesenchymal transition (EMT) and inflammation in mice exposed to PA coal. RESULTS: Calcite rapidly eliminated BAI in an aqueous suspension of PA coal. Ferritin induction in human lung epithelial cells exposed to PA coal was effectively eliminated by calcite. Mouse lung tissue markers indicated increased EMT after exposure to PA coal dust, but not after exposure to PA coal plus calcite. Markers of inflammation increased following exposure to PA coal alone, but not following exposure to PA coal plus calcite. CONCLUSION: Additional research may lead to the use of supplemental calcite in coal mining as a safe and effective way to prevent CWP among Appalachian coal miners. Am. J. Ind. Med. © 2012 Wiley Periodicals, Inc.American Journal of Industrial Medicine 09/2012; · 1.63 Impact Factor -
Article: Impairment of antioxidant defenses as a contributor to arsenite-induced cell transformation.
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ABSTRACT: Arsenite (As) causes transformation of human osteogenic sarcoma cells (HOS) when applied continuously at low doses (0.1-0.5 μM) during 8-weeks of exposure. However, the mechanisms by which As transforms human cells are not known. We investigated whether alterations occurred in gene expression and protein levels of antioxidant defense proteins, such as superoxide dismutase 1 (SOD1) and ferritin. In comparison to control HOS cells, 0.1 μM As induced greater cell proliferation and decreased anti-oxidant defenses. The tumor suppressor protein p53 was also decreased at both mRNA and protein levels. Further, pig3 (p53-induced-gene 3), a homolog of NQO1 (NADPH quinone oxidoreductase 1), was also down-regulated after 8 weeks of As challenge. The treatment of HOS cells with dicumarol, a NQO1 inhibitor, caused a dose-dependent decline in p53 protein levels, proving the effect of an antioxidant enzyme on p53 expression and, potentially, down-stream processes. Caffeic acid phenethyl ester, an antioxidant, prevented the As-induced decreases in SOD1, p53, and ferritin mRNA and protein levels. SOD1, p53 and ferritin levels were inversely related to As-induced cell proliferation. Cumulatively, these results strongly suggest that impairment in antioxidant defenses contributes to As-induced human cell transformation and that the p53 pathway is involved in the process.Biology of Metals 06/2012; 25(5):927-37. · 3.17 Impact Factor -
Article: 17β-Estradiol inhibits iron hormone hepcidin through an estrogen responsive element half-site.
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ABSTRACT: Interaction of estrogen with iron at the systemic level is long suspected, but direct evidence linking the two is limited. In the present study, we examined the effects of 17β-estradiol (E2) on hepcidin, a key negative regulator of iron absorption from the liver. We found that transcription of hepcidin was suppressed by E2 treatment in human liver HuH7 and HepG2 cells, and this down-regulation was blocked by E2 antagonist ICI 182780. Chromatin immunoprecipitation, deletion, and EMSA detected a functional estrogen responsive element half-site that is located between -2474 and -2462 upstream from the start of transcription of the hepcidin gene. After cloning the human hepcidin promoter into the pGL3Luc-Reporter vector, luciferase activity was also down-regulated by E2 treatment in HepG2 cells. E2 reduced hepcidin mRNA in wild-type mice as well as in hemochromatosis Fe gene knockout mice. In summary, our data suggest that hepcidin inhibition by E2 is to increase iron uptake, a mechanism to compensate iron loss during menstruation. This mechanism may also contribute to increased iron stores in oral contraceptive users.Endocrinology 04/2012; 153(7):3170-8. · 4.46 Impact Factor -
Article: Protection against ultraviolet A-induced oxidative damage in normal human epidermal keratinocytes under post-menopausal conditions by an ultraviolet A-activated caged-iron chelator: a pilot study.
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ABSTRACT: Human skin is constantly exposed to ultraviolet A (UVA), which can generate reactive oxygen species and cause iron release from ferritin, leading to oxidative damage in biomolecules. This is particularly true in post-menopausal skin due to an increase in iron as a result of menopause. As iron is generally released through desquamation, the skin becomes a main portal for the release of excess iron in this age group. In the present study, we examined a strategy for controlling UVA- and iron-induced oxidative stress in skin using a keratinocyte post-menopausal cellular model system. Keratinocytes that had been cultured under normal or high-iron, low-estrogen conditions were treated with (2-nitrophenyl) ethyl pyridoxal isonicotinoyl hydrazone (2-PNE-PIH). 2-PNE-PIH is a caged-iron chelator that does not normally bind iron but can be activated by UVA radiation to bind iron. Following incubation with 2-PNE-PIH, the cells were exposed to 5 J/cm² UVA and then measured for changes in lipid peroxidation and ferritin levels. 2-PNE-PIH protected keratinocytes against UVA-induced lipid peroxidation and ferritin depletion. Further, 2-PNE-PIH was neither cytotoxic nor did it alter iron metabolism. 2-PNE-PIH may be a useful deterrent against UVA-induced oxidative stress in post-menopausal women.Photodermatology Photoimmunology and Photomedicine 10/2011; 27(5):231-5. · 1.30 Impact Factor -
Article: Oral contraceptive use, iron stores and vascular endothelial function in healthy women.
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ABSTRACT: Increased iron stores are associated with greater cardiovascular risk in postmenopausal women. Oral contraceptive pill (OCP) use decreases the volume of menstrual blood loss and increases iron stores, but the link between OCP use, iron stores and cardiovascular risk in premenopausal women has not been characterized. We conducted a cross-sectional study of 23 healthy OCP users to determine the association between type and duration of OCP exposure, iron stores, and vascular endothelial function [flow-mediated dilation (FMD) in the brachial artery]. Median duration of OCP use was 45 months. FMD in the brachial artery was significantly associated with progestin type used (estranes/gonanes vs. drospirenone) and duration of OCP use (both p<.05) but not iron stores. In multivariate analysis, progestin type was the only independent predictor of FMD. Use of OCP containing drospirenone was independently associated with greater FMD in the brachial artery and, thus, a potentially more favorable cardiovascular risk profile, when compared with use of OCP containing estranes/gonanes.Contraception 09/2011; 84(3):285-90. · 2.72 Impact Factor
