Oxalate deposition on asbestos bodies

• Published in: Human pathology 2003-08, Vol.34 (8), p.737-742
• Main Authors: Ghio, Andrew J, Roggli, Victor L, Richards, Judy H, Crissman, Kay M, Stonehuerner, Jacqueline D, Piantadosi, Claude A
• Format: Article
• Language: English
• Subjects: Acids; Asbestos; Asbestos, Crocidolite - adverse effects; Asbestos, Crocidolite - chemistry; Asbestos, Crocidolite - metabolism; Asbestosis - etiology; Asbestosis - metabolism; Asbestosis - pathology; Ascorbic Acid - chemistry; Biological and medical sciences; Calcium Oxalate - analysis; Calcium Oxalate - chemistry; Calcium Oxalate - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; Crystallization; Crystallography, X-Ray; Crystals; Deferoxamine - chemistry; Deposition; Diet; Fatal Outcome; Free radicals; Health sciences; Humans; Hydrogen Peroxide - chemistry; Inorganic dusts (pneumoconiosises) and organic dusts (byssinosis etc.); iron; Iron - chemistry; Iron Chelating Agents - chemistry; Kidney stones; Lung - metabolism; Lung - pathology; Male; Medical sciences; Middle Aged; oxalate; Oxidation-Reduction; Oxygen therapy; Scanning electron microscopy; Thiourea - analogs & derivatives; Thiourea - chemistry; Toxicology
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/S0046-8177(03)00252-1

We report on a deposition of oxalate crystals on ferruginous bodies after occupational exposure to asbestos demonstrated in 3 patients. We investigated the mechanism and possible significance of this deposition by testing the hypothesis that oxalate generated through nonenzymatic oxidation of ascorbate by asbestos-associated iron accounts for the deposition of the crystal on a ferruginous body. Crocidolite asbestos (1000 μg/mL) was incubated with 500 μmol H 2O 2 and 500 μmol ascorbate for 24 hours at 22°C. The dependence of oxalate generation on iron-catalyzed oxidant production was tested with the both the metal chelator deferoxamine and the radical scavenger dimethylthiourea. Incubation of crocidolite, H 2O 2, and ascorbate in vitro generated approximately 42 nmol of oxalate in 24 hours. Oxalate generation was diminished significantly by the inclusion of either deferoxamine or dimethylthiourea in the reaction mixture. Incubation of asbestos bodies and uncoated fibers isolated from human lung with 500 μmol H 2O 2 and 500 μmol ascorbate for 24 hours at 22°C resulted in the generation of numerous oxalate crystals. We conclude that iron-catalyzed production of oxalate from ascorbate can account for the deposition of this crystal on ferruginous bodies.