title: Chronic exposure to cadmium did not impair vitamin D metabolism in monkeys.
abstract: Vitamin D metabolism in primates with chronic exposure to cadmium was studied in relation to Itai-Itai disease. In a series of experiments, crab-eating monkeys were fed cadmium-contaminated rice (1.33 micrograms Cd/g) or a diet containing 3 micrograms/g cadmium chloride for 6 years. These treatments had no effect on the 1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D (24,25(OH)2D), and 25-hydroxyvitamin D (25(OH)D) in the serum. This is consistent with unchanged production of 1,25(OH)2D and 24,25(OH)2D by renal mitochondria prepared from the same animals. No indication of renal dysfunction was observed. In another series of experiments, rhesus monkeys were fed a diet containing 3, 10, 30, or 100 micrograms/g cadmium for 9 years. Serum vitamin D metabolites and renal production of 24,25(OH)2D also remained unchanged. In contrast, renal 25(OH)D-1-hydroxylase (1-hydroxylase), which is responsible for the production of 1,25(OH)2D, seemed to be suppressed in the animals fed 30 or 100 micrograms/kg cadmium-contaminated diet (no statistical significance). These animals had indications of mild renal dysfunction, and there was a strong negative correlation between 1-hydroxylase and urinary concentration of either protein or beta 2-microglobulin. These data suggest a slight change in the total enzyme activity, possibly due to mild renal dysfunction. Since substrate (25(OH)D) concentration is much lower and thus rate-limiting in vivo as compared with that in vitro assay system used in this study, the slight change of enzyme activity would not have been sufficient to affect the serum level of 1,25(OH)2D. No skeletal abnormality was observed in any of these animals. In view of these data, the length of cadmium exposure and the life span of animals as well as epidemiological data published elsewhere, factors other than cadmium may also be involved in the development of Itai-Itai disease.
authors.affiliation: Department of Pharmacology, Jichi Medical School, Tochigi-ken, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kawashima
authors.forename: H
authors.initials: H
authors.lastname: Nomiyama
authors.forename: K
authors.initials: K
authors.lastname: Nomiyama
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects; D002104:Cadmium / Q000378:metabolism / Q000633:toxicity*; D002136:Calcium, Dietary / Q000008:administration & dosage; D006900:Hydroxylation; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D011507:Proteinuria / Q000139:chemically induced; D014807:Vitamin D / Q000378:metabolism*; D001613:beta 2-Microglobulin / Q000652:urine
chemical_list: D002136:Calcium, Dietary; D001613:beta 2-Microglobulin; D002104:Cadmium; D014807:Vitamin D