title: Depletion of iron and ascorbate in rodents diminishes lung injury after silica.
abstract: Exposures of the lung to iron chelates can be associated with an injury. The catalysis of oxygen-based free radicals is postulated to participate in this injury. Such oxidant generation by mineral oxide particles can be dependent on availability of both iron and a reductant. We tested the study hypothesis that lung injury after silica is associated with the availability of both iron and ascorbate in the host by depleting this metal and reductant in the lungs of rats and guinea pigs, respectively. Rats were fed either a normal diet or a diet deficient of iron. After 30 days, animals were instilled with either saline or 1.0 mg Minusil-5 silica. Relative to saline, silica significantly increased neutrophils and lavage protein. Iron depletion significantly diminished both the cellular influx and injury but only at 1 week after silica exposure. Guinea pigs were provided either a normal diet supplemented with 1,000 ppm vitamin C or a diet deficient in ascorbate. After 14 days, the guinea pigs were instilled with either saline or 1.0 mg silica. Silica exposure significantly increased neutrophils and lavage protein. Ascorbate depletion significantly diminished the influx of inflammatory cells and injury at both 1 day and 1 week after silica exposure. We conclude that host concentrations of both iron and ascorbate can affect lung injury after silica exposure.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Ghio
authors.forename: T P
authors.initials: TP
authors.lastname: Kennedy
authors.forename: K M
authors.initials: KM
authors.lastname: Crissman
authors.forename: J H
authors.initials: JH
authors.lastname: Richards
authors.forename: G E
authors.initials: GE
authors.lastname: Hatch
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001206:Ascorbic Acid Deficiency / Q000378:metabolism*; D004032:Diet; D004195:Disease Models, Animal; D004391:Dust; D007501:Iron / Q000378:metabolism*; D000090463:Iron Deficiencies; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000633:toxicity*; D012829:Silicosis / Q000517:prevention & control*
chemical_list: D004391:Dust; D012822:Silicon Dioxide; D007501:Iron; D001205:Ascorbic Acid