Effects of polyhalogenated aromatic hydrocarbons on vitamin A catabolism and the regulation of vitamin A homeostasis in rats

Thesis/Dissertation · Sat Dec 31 23:00:00 EST 1988

OSTI ID:6317575

Bank, P A

Polyhalogenated aromatic hydrocarbons (PHAH) are known to adversely affect vitamin A status resulting in the hepatic depletion and enhanced excretion of vitamin A. Increased renal and serum vitamin A content occurs subsequent to these PHAH-related alterations. Vitamin A, a highly regulated system, appears to undergo rapid compensatory changes to maintain homeostasis in response to nutritional, metabolic, or toxicologic conditions. The present study was undertaken in order to elucidate the mechanism(s) responsible for these PHAH-related effects on vitamin A homeostasis. To this end, the toxin prototype of the PHAH class 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the 3,4,5,3{prime},4{prime},5{prime}-hexabromo- or hexachloro-biphenyls were used in this study. Results presented in this study indirectly showed that PHAH caused enhanced hepatic and extrahepatic catabolism of intravenously administered {sup 3}H-retinol-retinol binding protein-transthyretin as evidenced by increased inactive polar retinoids in liver, kidney, bile, and excreta. These polar retinoids were isolated from tissues and bile and are thought to represent oxidized and/or glucuronidated, elimination metabolites of vitamin A. PHAH increased the microsomal activity of cytochrome P-450 MFO and UDP-glucuronosyl transferase toward retinoic acid (RA), enzyme systems that are also known to be coordinately induced by PHAH. Increased serum and kidney vitamin A is likely a homeostatic response to PHAH-related increased target tissue catabolism. For serum, this was shown directly by the finding that PHAH caused decreased liver esterification of retinol recycled from the extrahepatic tissues and indirectly by the administration of the active target tissue metabolite, RA. After RA, both control and PHAH-treated rats lowered their serum vitamin A.

• Research Organization: Michigan Univ., Ann Arbor, MI (USA)
• OSTI ID: 6317575
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
AROMATICS
BIOLOGICAL EFFECTS
CARBOXYLIC ACID ESTERS
CATABOLISM
CELL CONSTITUENTS
ENZYME ACTIVITY
ENZYMES
ESTERS
HOMEOSTASIS
HYDROCARBONS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
MAMMALS
METABOLISM
MICROSOMES
MIXED-FUNCTION OXIDASES
ORGANIC COMPOUNDS
ORGANOIDS
OXIDOREDUCTASES
OXYGENASES
POLYCYCLIC AROMATIC HYDROCARBONS
RATS
RETINOIC ACID
RIBOSOMES
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES
VITAMIN A
VITAMINS