Alterations in vitamin A metabolism by polyhalogenated aromatic hydrocarbons

Abstract

Adequate stores and adequate tissue levels of vitamin A are maintained by a balance of tissue demands and dietary intake of the vitamin and are modified by many factors, including xenobiotics. It is well established that exposure to polyhalogenated aromatic hydrocarbons (PHAH) decreases hepatic content of vitamin A. Recent findings indicate that hepatic depletion of vitamin A is accompanied by an increase in serum and renal vitamin A content and enhanced excretion of vitamin A metabolites in urine and feces. Examination of tissue retinoid profiles reveals that PHAH exposure causes the generation of increased amounts of polar retinoids. It is very likely that PHAH affect enzymes crucial for regulation of vitamin A storage as well as enhance activities of specific enzymes in vitamin A metabolic pathway.

Vitamins A1, A2, and E in minks exposed to polychlorinated biphenyls (Aroclor 1242®) and copper, VIA diet based on freshwater or marine fish

“…It has been suggested that enzymatic reactions, such as cytochrome P‐450 mono‐oxygenase functions induced by the PCBs, consume vitamin A [8,12,31]. In addition, in rodents the increased output of vitamin A and its polar metabolic products via blood filtration in the kidney and excretion in urine have been suggested to contribute heavily to the decreased stores of vitamin A in the liver [12,13]. In the subchronic exposure of this study, the hepatic stores of analog A 2 were significantly decreased in those minks on the freshwater diet.…”

“…The only series of experiments conducted with mink [9,10] showed a decrease in hepatic vitamin A 1 with Clophen A50 (commercial PCB mixture, Bayer, LeVerkusen, Germany) but not after exposure to Aroclor 1254. It has been suggested that enzymatic reactions, such as cytochrome P‐450 mono‐oxygenase functions induced by the PCBs, consume vitamin A [8,12,31]. In addition, in rodents the increased output of vitamin A and its polar metabolic products via blood filtration in the kidney and excretion in urine have been suggested to contribute heavily to the decreased stores of vitamin A in the liver [12,13].…”

“…Kidneys play an important role in vitamin A recycling. In rodent experiments [12,30,33], where the amount of hepatic vitamin A has decreased because of PCBs, increases in this vitamin were detected in the kidneys. Apparently, mobilized and subsequently excreted vitamin A is partly retained in the kidneys.…”

“…As in experiments with rodents, seals, and primates [8], PCBs have been found to disturb the vitamin A metabolism of mink [9,10]. In general, several symptoms of PCB administration (decreased growth, impaired reproduction, decreased integrity of epithelial growth, and depressed immune function) are the same as those found in vitamin A deficiency [5,11,12]. Therefore, the mechanism by which PCBs exert their influence and the role of vitamin A in this process have been of great interest.…”

Effects of a Technical PCB Preparation and Fractions Thereof on Ethoxyresorufin O‐Deethylase Activity, Vitamin A Levels and Thymic Development in the Mink (Mustela vison)*

“…In many animal species treatment with Ah receptor ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and coplanar PCBs, leads to enhancement of aryl hydrocarbon (benzo[a]pyrene) hydroxylase (AHH) and 7-ethoxyresorufin 0-deethylase (EROD) activities (Poland et ul. 1976;Poland & Knutson 1982;Brunstrom & Andersson 1988), reduction of vitamin A concentrations in various organs ( Zile et al 1989), and thymic atrophy (hypoplasia in developing individuals) (Vos & Luster 1989).…”