Effect of tetrachlorodibenzo-p-dioxin (TCDD) on the glucuronidation of retinoic acid in the rat.
Administration of a single oral dose (10 micrograms/kg) of tetrachlorodibenzo-p-dioxin (TCDD) caused a 33% decrease in retinyl esters in the livers of male rats, but a 13-fold increase in retinyl esters in the kidney and a 3-fold increase in serum retinol. Liver and kidney microsomal uridine diphosphoglucuronosyltransferase (UDPGT) activity toward all-trans-retinoic acid was increased 3.7- and 2.6-fold, respectively, ten days following exposure to TCDD. Verification of the in vitro formation of [3H]retinoyl beta-glucuronide (RG) was by cochromatography with authenic RG on reversed phase high pressure liquid chromatography (HPLC), identification of retinoic acid as the hydrolysis product after beta-glucuronidase treatment, and the characterization of the all-trans-retinoyl glucuronide by negative fragment mass spectroscopy, fast atom bobardment. We conclude that increased retinoic acid glucuronidation may be a contributing factor to the hepatic depletion of vitamin A and the increased excretion of vitamin A metabolites following TCDD exposure.
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Department of Food Science and Human Nutrition, Michigan State University, East Lansing 48824-1224.
Salyers
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Zile
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D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004147:Dioxins / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014212:Tretinoin / Q000031:analogs & derivatives* / Q000378:metabolism*; D014801:Vitamin A / Q000302:isolation & purification / Q000378:metabolism*; D014802:Vitamin A Deficiency / Q000378:metabolism
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D014801:Vitamin A; C026787:retinoyl glucuronide; D014212:Tretinoin; D014453:Glucuronosyltransferase