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Role of high density lipoproteins in the biodistribution of two radioiodinated probes in the rat

Journal Article · · Toxicol. Appl. Pharmacol.; (United States)
;

Two radioiodinated probes, /sup 125/I-cholesteryl oleate (/sup 125/I-CO), a derivative of a natural constituent of lipoproteins, and 1-(2-chlorophenyl)-1-(4(/sup 125/I)iodophenyl)-2,2-dichlorethane (/sup 125/I-DDD), an analog of the adrenolytic drug o,p'-DDD (mitotane), were selected to study the role of lipoproteins in drug disposition and to examine the ability of these vehicles to direct foreign molecules to specific tissues. In vivo and in vitro techniques were utilized to associate these probes with rat high density lipoproteins (HDL). Tissue distribution studies indicated that prior incorporation of /sup 125/I-CO into rat HDL increased the uptake of /sup 125/I-CO by rat adrenal, which was dramatically enhanced when this preparation was administered to animals made hypolipidemic with 4-aminopyrazolo(3,4-d)-pyrimidine (4-APP). Acetylation of HDL labeled with /sup 125/I-CO provided evidence that the observed uptake into the adrenal was via a receptor-mediated process. In contrast with these results, prior association of /sup 125/I-DDD with rat HDL failed to alter the ability of this compound to accumulate in adrenal tissue of normal or hypolipidemic animals. Polyacrylamide gel electrophoresis (PAGE) was utilized to examine the stability of the association of /sup 125/I-CO and /sup 125/I-DDD with rat HDL. These results suggested that /sup 125/I-CO was associated with the lipophilic core of HDL, whereas /sup 125/I-DDD appeared to be partially associated with the surface components of HDL. Saturation of surface components with stable o,p'-DDD offered data to suggest that this binding to apoproteins may disrupt the normal receptor-mediated uptake process.

Research Organization:
Univ. of Michigan Medical School, Ann Arbor
OSTI ID:
5779474
Journal Information:
Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 77:1; ISSN TXAPA
Country of Publication:
United States
Language:
English

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL GLANDS
BETA DECAY RADIOISOTOPES
BIOCHEMISTRY
BODY
CARBOXYLIC ACIDS
CHEMISTRY
CHOLESTEROL
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
ELECTROPHORESIS
ENDOCRINE GLANDS
GLANDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIPIDS
LIPOPROTEINS
MONOCARBOXYLIC ACIDS
NUCLEI
ODD-EVEN NUCLEI
OLEIC ACID
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PROBES
PROTEINS
RADIOISOTOPES
RECEPTORS
STEROIDS
STEROLS
TISSUE DISTRIBUTION
TRACER TECHNIQUES
UPTAKE