Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-30T18:58:46.112Z Has data issue: false hasContentIssue false
  • English
  • Français

A comparative study on the effects of oral amiodarone and trimeprazine, two in vitro retinyl ester hydrolase inhibitors, on the metabolic availability of vitamin A in rats

Published online by Cambridge University Press:  08 March 2007

Rainer Schindler ,
Tanja Fielenbach  and
Gerhard Rave
Rainer Schindler*
Affiliation:
Department of Human Nutrition and Food Science, Christian-Albrechts-University zu Kiel, D-24 116, Germany
Tanja Fielenbach
Affiliation:
Department of Human Nutrition and Food Science, Christian-Albrechts-University zu Kiel, D-24 116, Germany
Gerhard Rave
Affiliation:
Institute for Variationsstatistik, Christian-Albrechts-University zu Kiel, D-24 116, Germany
*
*Corresponding author: Dr R. Schindler, fax +49 431 880 5679, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Amiodarone, an antiarrhythmic drug, and trimeprazine, an antipsychotic drug, are both in vitro inhibitors of retinyl ester hydrolase. To determine whether these agents have deleterious effects on aspects of vitamin A metabolism, Brown Norway rats (n 18) were treated at clinically equivalent doses once daily for 26d with either oral drug. On day 27, a tolerance test was used to determine whether these agents interfered with vitamin absorption. During the first 8d, the plasma retinol level declined in all animals. Between days 12 and 27, it rose to near pre-treatment concentrations in the control and trimeprazine groups and remained relatively constant at low levels (P<0·001) in the amiodarone group. The intestinal absorption of vitamin A was reduced (P<0·05) in the amiodarone group compared with the placebo and trimeprazine groups, which did not differ significantly from each other. At the end of the 4-week treatment period, hepatic retinyl ester hydrolase activity was lower in the drug-dosed rats (P=0·06 for amiodarone) than in the controls. With regard to effects on liver reserves, drug treatment resulted in vitamin A depletion (P<0·019), and distinctive patterns of retinol and its esters were seen in response to dosing. In conclusion, amiodarone and trimeprazine have been shown to influence different aspects of retinoid metabolism, namely absorption, storage and transport. In clinical practice, the routine unmonitored use of these drugs and the suggestion that these agents be taken with meals are not recommended.

Keywords

Amiodarone–vitamin A interactionTrimeprazine–vitamin A interactionRetinyl ester hydrolase
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 5 , November 2005 , pp. 675 - 683
Copyright
Copyright © The Nutrition Society 2005

References

Blaner, WS, Hendriks, HFJ, Brouwer, A, Leeuw, AM, Knook, DL & Goodman, DS (1985) Retinoids, retinoid-binding proteins, and retinyl palmitate hydrolase distribution in different types of rat liver cells. J Lipid Res 26, 1241–1251.CrossRefGoogle ScholarPubMed
Blomhoff, R, Helgerud, P, Rasmussen, M, Berg, T & Norum, KR (1982) In vivo uptake of chylomicron (3H) retinyl ester by rat liver: evidence for retinol transfer from parenchymal to nonparenchymal cells. Proc Natl Acad Sci 79, 7326–7330.CrossRefGoogle ScholarPubMed
Blomhoff, R, Rasmussen, M & Nilsson, A (1985) Hepatic retinol metabolism. J Biol Chem 260, 13560–13565.CrossRefGoogle ScholarPubMed
Bradford, MM (1976) Rapid and sensitive method for quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248–254.CrossRefGoogle ScholarPubMed
Congdon, NG & West, KP (1999) Nutrition and the eye. Curr Opinion Ophthalmol 10, 464–473.CrossRefGoogle ScholarPubMed
Cooper, DA & Olson, JA (1986) Properties of liver retinyl ester hydrolase in young pigs. Biochim Biophys Acta 884, 251–258.CrossRefGoogle ScholarPubMed
Coutselinis, A, Dimopoulos, G & Dritsas, C (1974) Fatal intoxication with chlorpromazine with special regard to the influence of putrefaction on its toxicological analysis. Forensic Sci 4, 191–194.CrossRefGoogle Scholar
Dollery, C (1991a) Therapeutic Drugs, vol. 1, pp. A90–A94. Edinburgh: Churchill Livingstone.Google Scholar
Dollery, C (1991b) Therapeutic Drugs, vol. 2, pp. T141–T145. Edinburgh: Churchill Livingstone.Google Scholar
Edler, K, Gottfries, G, Haslund, J & Ravn, J (1971) Eye changes in connection with neuroleptic treatment especially concerning phenothiazines and thioxanthenes. Acta Psychiatr Scand 47, 377–384.CrossRefGoogle ScholarPubMed
Flach, AJ, Dolan, BJ, Sudduth, B & Weddell, J (1983) Amiodarone-induced lens opacities. Arch Ophthalmol 101, 1554–1556.CrossRefGoogle ScholarPubMed
Freedman, MD & Somberg, JC (1991) Pharmacology and pharmacokinetics of amiodarone. J Clin Pharmacol 31, 1061–1069.CrossRefGoogle ScholarPubMed
Gofferje, H (1978) Prealbumin and retinol-binding protein – highly sensitive parameters for the nutritional state in respect of protein. Med Lab 5, 38–44.Google Scholar
Goodman, DS & Blaner, WS (1984) Biosynthesis, absorption, and hepatic metabolism of retinol. In The Retinoids, vol. 2, pp. 1–39 [Sporn, AB, Roberts, MB and Goodman, DS, editors]. Orlando, FL: Academic Press.Google Scholar
Harris, L & Roncucci, R (1986) Amiodarone. Paris: Médecine et Science Internationales.Google Scholar
Harrison, EH (1998) Lipases and carboxylesterases: possible roles in the hepatic metabolism of retinol. Annu Rev Nutr 18, 259–276.CrossRefGoogle ScholarPubMed
Haubold, H, Loew, W & Kolb, E (1953) Einwirkung von Penicillin auf den Vitamin A –Gehalt des Serums sowie auf die Nachtsichtigkeit. Münchner Med Wochenschr 95, 792–796.Google Scholar
Helgerud, P, Petersen, LB & Norum, KR (1982) Acyl CoA: retinol acyltransferase in rat small intestine: its activity and some properties of the enzymic reaction. J Lipid Res 23, 609–618.CrossRefGoogle ScholarPubMed
Huang, HS & Goodman, DS (1985) Vitamin A and carotenoids. J Biol Chem 240, 2839–2844.CrossRefGoogle Scholar
Ingenbleek, Y, van den Schrieck, HG, de Nayer, P & de Visscher, M (1975a) The role of retinol-binding protein in protein-caloric malnutrition. Metabolis 24, 633–641.CrossRefGoogle Scholar
Ingenbleek, Y, van den Schrieck, HG, de Nayer, P & de Visscher, M (1975b) Albumin, transferrin and the thyroxine-binding prealbumin/retinol-binding protein complex in assessment of malnutrition. Clin Chim Acta 63, 61–67.CrossRefGoogle ScholarPubMed
Ito, YL, Zile, M, Ahrens, H & DeLuca, HF (1974) Liquid–gel partition chromatography of vitamin A compounds: formation of retinoic acid from retinyl acetate in vivo. J Lipid Res 15, 517–524.CrossRefGoogle ScholarPubMed
Kim, T-J & Park, J-S (1992) Identification of new urinary metabolites of trimeprazine in rats by gas chromatography-mass spectrometry. J Chromatogr 575, 295–300.CrossRefGoogle ScholarPubMed
Kintz, P, Berthault, F, Tracqui, A & Mangin, P (1995) A fatal case of alimemazine poisoning. J Anal Toxicol 19, 591–593.CrossRefGoogle ScholarPubMed
Lalloz, M, Byfield, P & Himsworth, R (1984) Binding of amiodarone by serum proteins and the effects of drugs, hormones, and other interacting ligands. J Pharm Pharmacol 36, 366–372.CrossRefGoogle ScholarPubMed
Latini, R, Tognoni, G & Kates, C (1984) Clinical pharmacokinetics of amiodarone. Clin Pharmacokinet 9, 136–156.CrossRefGoogle ScholarPubMed
Leo, MA & Lieber, CS (1985) New pathways for retinol metabolism in liver microsomes. J Biol Chem 260, 5228–5231.CrossRefGoogle ScholarPubMed
Leo, MA, Lowe, N & Lieber, CS (1987) Potentiation of ethanol-induced hepatic vitamin A depletion by phenobarbital and butylated hydroxytoluene. J Nutr 117, 70–76.CrossRefGoogle ScholarPubMed
Lombardo, D & Guy, O (1980) Studies on the substrate specificity of a carboxyl ester hydrolase from human pancreatic juice. II. Action on cholesterol esters and lipid-soluble vitamin esters. Biochim Biophys Acta 611, 147–155.CrossRefGoogle ScholarPubMed
Löscher, W, Ungemach, FR & Kroker, R (1991) Grundlagen der Pharmakotherapie bei Haus- und Nutztieren. Berlin: Verlag Paul Parey.Google Scholar
MacDonald, PN & Ong, DE (1988) Evidence for a lecithin–retinol acyltransferase activity in the rat small intestine. J Biol Chem 263, 12478–12482.CrossRefGoogle ScholarPubMed
Martin-Algarra, RV, Pascual-Costa, RM, Merino, M & Casabo, VG (1997) Intestinal absorption kinetics of amiodarone in rat small intestine. Biopharm Drug Dis 18, 523–532.3.0.CO;2-2>CrossRefGoogle ScholarPubMed
Morales, AI, Barata, JD, Bruges, M, Arevalo, MAGonzalez de Buitrage, JM, Palma, P, Branco, P & Perez-Barriocanal, F (2003) Acute renal toxic effects of amiodarone in rats. Pharmacol Toxicol 92, 39–42.CrossRefGoogle ScholarPubMed
Mutschler, E & Schäfer-Korting, M (1996) Arzneimittelwirkungen, 7th ed., Stuttgart: Wissenschaftliche Verlagsgesellschaft.Google Scholar
Napoli, JL & Race, KR (1990) Microsomes convert retinol and retinal into retinoic acid and interfere in the conversion catalyzed by cytosol. Biochim Biophys Acta 1034, 228–232.CrossRefGoogle ScholarPubMed
Physicians’ Desk Reference (1996) Montvale: Medical Economics.Google Scholar
Rechigl, M, Berger, S, Loosli, JK & Williams, HH (1962) Dietary protein and utilization of vitamin A. J Nutr 76, 435–440.CrossRefGoogle Scholar
Reynolds, JEF (1989) Martindale – The Extra Pharmacopeia. London: Pharmaceutical Press.Google Scholar
Rigtrup, KM, McEwen, LR, Said, HM & Ong, DE (1994) Retinyl ester hydrolytic activity associated with human intestinal brush border membranes. Am J Clin Nutr 60, 111–116.CrossRefGoogle ScholarPubMed
Roberts, AB, Lamb, LC & Sporn, MB (1980) Metabolism of all-trans retinoic acid in hamster liver microsomes. Oxidation of 4-hydroxy to 4-keto retinoic acid. Arch Biochem Biophys 199, 374–383.CrossRefGoogle ScholarPubMed
Sauvage, MF, Rousseau, A, Marquet, P, Dumeirain, F, Raby, C & Lachâtre, G (1999) In vitro and in vivo study of the antithyroid side effects of trimeprazine. Toxicol Appl Pharmacol 158, 125–131.CrossRefGoogle ScholarPubMed
Schindler, R (2001) Inhibition of purified pig and human liver retinyl ester hydrolase by pharmacologic agents. Lipids 36, 543–548.CrossRefGoogle ScholarPubMed
Schindler, R, Fielenbach, T & Rave, G (2004) Flupenthixol and cefotiam: effects on vitamin A metabolism in rats. Brit J Nutr 92, 597–605.CrossRefGoogle ScholarPubMed
Schindler, R, Fielenbach, T, Rave, G, Blömer, A & Kellersmann, R (2002) Vitamin A metabolism is altered in Brown Norway and Long-Evans rats infused with naftidrofuryl or erythromycin intravenously. Int J Vitam Nutr Res 72, 210–220.CrossRefGoogle ScholarPubMed
Schindler, R, Klopp, A, Gorny, C & Feldheim, W (1985) Comparison between three fluorometric micromethods for determination of vitamin A in serum. Internat J Vitam Nutr Res 55, 25–34.Google ScholarPubMed
Schindler, R, Mentlein, R & Feldheim, W (1998) Purification and characterization of retinyl ester hydrolase as a member of the non-specific carboxylesterase supergene family. Eur J Biochem 251, 863–873.CrossRefGoogle ScholarPubMed
Schindler, R, Scholz, M & Feldheim, W (1987) Determination of vitamin A in liver sausage and liver tissue from slaughtered animals using HPLC. Z Lebensm Unters Forsch 185, 208–212.CrossRefGoogle ScholarPubMed
Shetty, PS, Watrasiewics, KE, Jung, RT & James, WPT (1979) Rapid-turnover transport protein: an index of subclinical protein-energy malnutrition. Lancet ii, 230–232.CrossRefGoogle Scholar
Sirajudeen, KNS, Selvi, RT, Babakrishnan, DH & Devaraj, NS (2000) Effect of amiodarone on the membrane bound enzymes of rat intestine. Drug Chem Toxicol 23, 387–400.CrossRefGoogle ScholarPubMed
Smith, JE, DeMoor, LM, Green, EL & Ritter, SJ (1998) The complex between retinol and retinol-binding protein is formed in the rough microsomes of liver following repletion of vitamin A-depleted rats. Biochem Biophys Acta 1380, 10–20.CrossRefGoogle ScholarPubMed
Tsin, ATC & Lam, K-W (1986) Retinyl palmitate hydrolase activity in the bovine retina. Biochem Biophys Res Comm 134, 1209–1214.CrossRefGoogle ScholarPubMed
Veronese, ME, McLean, S & Hendricks, R (1988) Plasma protein binding of amiodarone in a patient population: measurement by erythrocyte partitioning and a novel glass-binding method. Br J Clin Pharmacol 26, 721–731.CrossRefGoogle Scholar
Yeum, K-J, Shang, F, Schalch, W, Russell, RM & Taylor, A (1999) Fat-soluble nutrient concentrations in different layers of human cataractous lens. Curr Eye Res 19, 502–505.CrossRefGoogle ScholarPubMed
Young, RA & Mehendale, HM (1986) In vitro metabolism of amiodarone by rabbit and rat liver and small intestine. Drug Metabol Dispos 14, 423–429.Google ScholarPubMed