Defense of mammalian body against heavy metal-induced toxicities: Sequestration by the choroid plexus and elimination via the bile

Thesis/Dissertation · Tue Jan 01 04:00:00 EST 1991

OSTI ID:7013346

Zheng, Wei

Tissue sequestration and biliary elimination are two of the important mechanisms by which mammalian body defends against heavy metal insults. In rats or rabbits that had received Pb, Cd, Hg, As and [sup 210]Po, these metal ions were sequestered in the choroid plexus at concentrations of Pb, Cd, Hg, As and Po that were 57, 33, 12, 13 and 5 times higher, respectively, than those found in the brain cortex. In addition, the concentrations of these heavy metal ions were many fold greater in the choroid plexus than in the CSF or blood. The accumulation of Pb in the choroid plexus was dose-dependent and time-related. When the choroid plexus was incubated, in vitro, with ouabain, the latter significantly inhibited the uptake of Cd from the CSF side of the choroid plexus. Cystine concentration was four times greater in the choroid plexus than in brain cortex. Results suggest that the choroid plexus sequesters toxic metal and metalloid ions. It appears to do this in order to protect the CSF and brain from toxic heavy metals in the blood. The effects of N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA), meso-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-1-propane sulfonic acid (DMPS) on biliary excretion of Cd was studied in rat chronic intoxication mode. DMPA (0.10 mmol/kg, iv), when given to rats three days after exposure to Cd, elicited within 30 min a 20-fold increase in biliary Cd excretion. GSH in rat bile was also increased three fold as compared to control. Neither DMSA nor DMPS increased biliary Cd or GSH. Upon iv administration, DMPA, not DMSA, appeared in bile. An altered, presumably disulfide, form of DMPS was also found in bile. Incubation of DMPA or DMSA with Cd-saturated MT resulted in the removal of Cd from MT. DMPS, however, promoted the formation of MT polymers. DMPA protected biliary GSH from autoxidation.

• Research Organization: Arizona Univ., Tucson, AZ (United States)
• OSTI ID: 7013346
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALPHA DECAY RADIOISOTOPES
ANIMALS
ARSENIC
BILE
BIOLOGICAL ACCUMULATION
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BODY
BODY AREAS
BODY FLUIDS
CADMIUM
CEREBROSPINAL FLUID
CLEARANCE
DATA
DAYS LIVING RADIOISOTOPES
DETOXIFICATION
ELEMENTS
EVEN-EVEN NUCLEI
EXCRETION
EXPERIMENTAL DATA
EYES
FACE
HEAD
HEAVY NUCLEI
INFORMATION
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LEAD
MAMMALS
MATERIALS
MERCURY
METABOLISM
METALLOPROTEINS
METALLOTHIONEIN
METALS
NANOSEC LIVING RADIOISOTOPES
NUCLEI
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANS
POLONIUM 210
POLONIUM ISOTOPES
PROTEINS
RABBITS
RADIOISOTOPES
RATS
RETENTION
RODENTS
SEMIMETALS
SENSE ORGANS
TOXICITY
UVEA
VERTEBRATES