Gastrointestinal and systemic uptake of bismuth in mice after oral exposure.
Bismuth compounds have been used in medicine for more than 200 years. In recent years, bismuth has gained renewed interest as a remedy for eradication of gastrointestinal pathogens, especially Helicobacter pylori. In this study we describe the anatomical distribution of bismuth in the gastrointestinal tract and other organs after oral exposure in a mouse model. After exposure of the experimental animals to ranitidine bismuth citrate or bismuth citrate, we used the autometallographic silver enhancement technique to demonstrate the presence of bismuth in tissue samples from the gastrointestinal tract, liver, spleen, thymus, kidney and lymph nodes. We exposed cultured murine peritoneal macrophages to bismuth citrate and examined the bismuth accumulation over time. We found that in the mouse bismuth is absorbed systemically after a single dose of either compound, ranitidine bismuth more easily than bismuth citrate. Uptake could be shown in the stomach, duodenum, ileum and kidney for hours after exposure. Weeks after the exposure, deposits of bismuth were found in lymph nodes, liver, spleen and kidney as well as in macrophages in the gastrointestinal lamina propria. At the subcellular level, bismuth was found exclusively in lysosomes, primarily in macrophages and dendritic cells. Subsequent analyses of macrophage cultures showed lysosomal accumulations to be time and dose dependent.
Larsen
Agnete
A
Department of Neurobiology, Institute of Anatomy, University of Aarhus, Denmark.
Martiny
Nargot
N
Stoltenberg
Meredin
M
Danscher
Gorm
G
Rungby
Jørgen
J
D000042:Absorption / Q000187:drug effects* / Q000502:physiology; D000284:Administration, Oral; D000818:Animals; D001729:Bismuth / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011899:Ranitidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013194:Staining and Labeling; D013997:Time Factors
D009942:Organometallic Compounds; C073340:ranitidine bismuth citrate; D011899:Ranitidine; C002791:bismuth tripotassium dicitrate; D001729:Bismuth