title: The effect of pharmacologically altered gastric pH on cadmium absorption from the diet and its accumulation in murine tissues.
abstract: Solubility of Cd in Cd-amended mouse chow in water was reduced by increased pH; even less Cd was solubilized by simulated digestion in vitro, where increased gastric phase pH decreased solubility, an effect that persisted following intestinal digestion at pH 5.5. These data suggested that increasing gastric pH in vivo pharmacologically would reduce Cd accumulation in target organs of mice treated with omeprazole (a proton-pump inhibitor) or cimetidine (a H2-receptor antagonist). This expectation was mostly not realized. Gastric pH in animals receiving Cd-amended diet was increased by omeprazole, but not cimetidine, relative to animals receiving no drugs, and Cd-amended diet. Tissue concentrations of Cd were similar among the three groups receiving Cd-amended diet, for liver, kidney and testes. Small intestine Cd concentration was lower for omeprazole-treated animals than for those receiving neither drug and Cd-amended diet, suggesting that omeprazole decreased Cd absorption by this organ. This effect may have been compensated for by increased uptake of complexed Cd by the large intestine, as accumulation in the liver, kidney and testes was not reduced. In vitro determinations of bioaccessible Cd in food may not predict in vivo bioaccumulation in all target organs.
authors.affiliation: Department of Land Resource Science, University of Guelph, ON, Canada N1G 2W1.
authors.forename: M
authors.initials: M
authors.lastname: Waisberg
authors.forename: W D
authors.initials: WD
authors.lastname: Black
authors.forename: D Y
authors.initials: DY
authors.lastname: Chan
authors.forename: B A
authors.initials: BA
authors.lastname: Hale
mesh_terms: D000042:Absorption / Q000187:drug effects; D000818:Animals; D001682:Biological Availability; D002104:Cadmium / Q000493:pharmacokinetics*; D002927:Cimetidine / Q000494:pharmacology*; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009853:Omeprazole / Q000494:pharmacology*; D009928:Organ Specificity; D011897:Random Allocation; D012995:Solubility; D013737:Testis / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D004791:Enzyme Inhibitors; D006635:Histamine H2 Antagonists; D002104:Cadmium; D002927:Cimetidine; D009853:Omeprazole