The effects of nonadecafluoro-n-decanoic acid on serum retinol and hepatic retinyl palmitate hydrolase activity in male Sprague-Dawley rats.
The effects of nonadecafluoro-n-decanoic acid (NDFDA) on serum retinol levels and hepatic retinyl palmitate hydrolase (RPH) activity were investigated in male Sprague-Dawley rats given a single intraperitoneal (IP) dose of 0, 50, or 100 mg/kg NDFDA and sacrificed at two, eight, or 11 days. Treated animals exhibited depressed serum retinol levels, lymphoid involution, and failure to gain weight in proportion to the dose. Hepatic RPH activities were depressed in both treatment groups at all time points and correlated with serum retinol levels. Hepatic retinol levels were also depressed by Day 11. Extraction of hepatic homogenates with acetone removed NDFDA and increased RPH activities twofold and threefold for the low- and high-dose groups, respectively. Analysis of partially purified RPH showed both NDFDA and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to be noncompetitive inhibitors: KI = 450 and 750 microM, respectively. We conclude that NDFDA causes a decrease in the mobilization of vitamin A from the liver by noncompetitive inhibition of RPH.
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Department of Biochemistry, Michigan State University, East Lansing 48824-1319.
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D000818:Animals; D001667:Binding, Competitive; D001835:Body Weight / Q000187:drug effects; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003652:Decanoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005466:Fluorocarbons / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008221:Lymphoid Tissue / Q000187:drug effects; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014801:Vitamin A / Q000378:metabolism*
D003652:Decanoic Acids; D005466:Fluorocarbons; D000072317:Polychlorinated Dibenzodioxins; C022521:retinol-palmitate esterase; D014801:Vitamin A; C036567:perfluorodecanoic acid; D002265:Carboxylic Ester Hydrolases