Hostname: page-component-cd9895bd7-7cvxr Total loading time: 0 Render date: 2024-12-23T15:43:18.243Z Has data issue: false hasContentIssue false
  • English
  • Français

Flupenthixol and cefotiam: effects on vitamin A metabolism in rats

Published online by Cambridge University Press:  09 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-24105, Germany
Tanja Fielenbach
Affiliation:
Department of Human Nutrition and Food Science, Christian-Albrechts-University zu Kiel, D-24105, Germany
Gerhard Rave
Affiliation:
Institute for Variationsstatistik, Christian-Albrechts-University zu Kiel, D-24105, Germany
*
*Corresponding author: Dr Rainer 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.

We examined the alterations in vitamin A metabolism as a result of flupenthixol or cefotiam administration. The impact of these drugs on indices of vitamin A status was evaluated in Brown Norway and Long–Evans rats. Intramuscular drug administration for 28 d resulted in a decline in systemic retinol. Changes in circulating retinol with time for chronic dosing showed drug treatment (P<0·001) and time (P<0·03) to be significant factors, but rat strain (P=0·33) was not a significant factor. Flupenthixol was the most active retinol-lowering compound (P<0·005). At the end of the 28 d period, hepatic retinyl ester hydrolase activity was greater in drug-treated rats than in controls (P<0·05). With regard to effects on liver reserves: (1) flupenthixol treatment resulted in vitamin A depletion (P<0·05); (2) cefotiam treatment stimulated vitamin A accumulation; (3) distinctive patterns of retinol and its esters were seen in response to treatment. It is reasonable to assume that the drugs interfere with vitamin A in at least two ways: (1) lowering of plasma retinol, an early event in the interaction, may be caused by inhibition of hepatic holo-retinol-binding protein secretion or stimulation of clearance, or both; (2) when plasma retinol levels are persistently low, and as the hepatic deposits of the xenobiotics build up, there are changes in the vitamin A pool size and composition of the liver. Candidate enzymes are retinyl ester hydrolase and cytochrome P450. The relationship between these two events will be studied in further detail.

Keywords

Flupenthixol–vitamin A interactionCefotiam–vitamin A interactionRetinyl ester hydrolase
Type
Research Article
Information
British Journal of Nutrition , Volume 92 , Issue 4 , October 2004 , pp. 597 - 605
Copyright
Copyright © The Nutrition Society 2004

References

Ahmad, M, Nicholls, PJ, Smith, HJ & Ahamadi, M (2000) Effect of P450 isozyme-selective inhibitors on in-vitro metabolism of retinoic acid by rat hepatic microsomes. J Pharm Pharmacol 52, 311–314.CrossRefGoogle ScholarPubMed
Azaïs, V, Rachman, F, Gros, S, Pascal, G, Amédée-Manesme, O (1987) Cyclosporine administration decreases liver vitamin A stores in normal and vitamin A-deficient rats. Drug Nutr Interact 5, 81–88.Google ScholarPubMed
Barnard, DL & Heaton, KW (1973) Bile acids and vitamin A absorption in man: the effect of two bile acid-binding agents, cholestyramine and lignin. Gut 14, 316–318.CrossRefGoogle ScholarPubMed
Bender, K, Adams, M & Baverstock, PR (1984) Biochemical markers in inbred strains of the rat ( Rattus norvegicus ). Immunogenetics 19, 257–266.CrossRefGoogle ScholarPubMed
Bhat, PV & Lacroix, A (1983) Separation and estimation of retinyl fatty acyl esters in tissue of normal rat by high-performance liquid chromatography. J Chromatogr 272, 269–278.CrossRefGoogle ScholarPubMed
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, 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
Brogard, JM, Jehl, F, Willemin, B, Lamalle, AM, Blickle, JF & Moteil, H (1989) Clinical pharmacokinetics of cefotiam. Clin Pharmacokinet 17, 163–174.CrossRefGoogle ScholarPubMed
Dollery, C (1991) Therapeutic Drugs, vol. 1, pp. F79–F83Edinburgh: Churchill Livingstone.Google Scholar
Faloon, WW, Paes, IC, Woolfolk, D, Nankin, H, Wallace, K & Haro, EN (1966) Effect of neomycin and kanamycin upon intestinal absorption. Ann NY Acad Sci 132, 879–887.CrossRefGoogle Scholar
Favaro, RMD, Silva, HS & Vannucchi, H (1994) Bioavailability of vitamin A in the rat following ingestion of neomycin sulfate or aluminium hydroxyde. Int J Vitam Nutr Res 64, 98–103.Google ScholarPubMed
Fernández, E, Borström, B (1990) Intestinal absorption of retinol and retinyl palmitate in the rat. Effect of tetrahydrolipstatin. Lipid 25, 549–552.CrossRefGoogle ScholarPubMed
Harrison, EH (1998) Lipases and carboxylesterases: possible roles in the hepatic metabolism of retinal. Annu Rev Nutr 18, 259–276.CrossRefGoogle Scholar
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
Hedrich, HJ (1990) Genetic Monitoring of Inbred Strains of Rats, pp. 322–332Stuttgart: Gustav Fischer Verlag.Google Scholar
Huang, HS & Goodman, DS (1985) Vitamin A and carotenoids. J Biol Chem 240, 2839–2844.CrossRefGoogle Scholar
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
Lahmame, A & Armario, A (1996) Differential responsiveness of inbred strains of rats to antidepressants in the forced swimming test: Are Wistar Kyoto rats an animal model of subsensitivity to antidepressants?. Psychopharmacology 123, 191–198.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 (1984) Decreased hepatic vitamin A after drug administration in men and in rats. Am J Clin Nutr 40, 1131–1136.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
Löscher, W, Ungemach, FR & Kroker, R (1991) Grundlagen der Pharmakotherapie bei Haus- und Nutztieren, pp 342–343Berlin and Hamburg: Verlag Paul Parey.Google Scholar
Martini, R & Murray, M (1993) Participation of P450 3A enzymes in rat hepatic microsomal retinoic acid 4-hydrolylation. Arch Biochem Biophys 303, 57–66.CrossRefGoogle Scholar
Mentlein, R & Heymann, E (1984) Hydrolysis of ester- and amide-type drugs by the purified isoenzymes of nonspecific carboxylesterase from rat liver. Biochem Pharmacol 33, 1243–1248.CrossRefGoogle ScholarPubMed
Mentlein, R & Heymann, E (1987) Hydrolysis of retinyl esters by non-specific carboxylesterases from rat liver endoplasmic reticulum. Biochem J 245, 863–867.CrossRefGoogle ScholarPubMed
Murray, M (1992) Inhibition and induction of cytochrome P450 2B1 in rat liver by promazine and chlorpromazine. Biochem Pharmacol 44, 1219–1222.CrossRefGoogle ScholarPubMed
Mutschler, E, Schäfer-Korting, M (1996) Arzneimittelwirkungen, 7th ed., pp. 670Stuttgart: Wissenschaftliche Verlagsgesellschaft mbH.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
Perry, CM & Brogden, RN (1996) Cefuroxime axetil. Drugs 52, 125–158.CrossRefGoogle ScholarPubMed
Pirovino, M, Honegger, U, Müller, O, Zysset, Th, Küpfer, A, Tinel, A & Pessayre, D (1990) Differences in hepatic drug accumulation and enzyme induction after chronic amiodarone feeding of two rat strains: role of the hydroxylator phenotype?. Br J Pharmacol 99, 35–40.CrossRefGoogle ScholarPubMed
Pitts, SM & Horvitz, JC (2000) Similar effects of D 1 /D 2 receptor blockade on feeding and locomotor behaviour. Pharmacol Biochem Behav 65, 433–438.CrossRefGoogle Scholar
Riegel, W, Hörl, WH (1993) Potenielle nephrotoxizität von cephalosporinen der 2. Generation: cefuroxim versus cefotiam. Infection 21, Suppl., S14–S16.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 Scholar
Samuel, P, Hobart, C & Shalchi, OB (1965) Serum cholesterol reduction by para-aminosalicylates in man. I-131 triolein absorption studies. Proc Soc Exp Biol Med 118, 654–658.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, Berndt, S, Schroeder, P, Oster, O, Rave, G, Sievers, H-H (2003) Plasma vitamin E and A changes during cardiopulmonary bypass and in the postoperative course. Langenbecks Arch Surg 387, 372–378.CrossRefGoogle Scholar
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, Klop, A, Gorny, C & Feldheim, W (1985) Comparison between three fluorometric micromethods for determination of vitamin A in serum. Int 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
Seifert, WF, Bosma, A, Hendricks, HFJ, Blaner, WS, van Leuwenvan, RE, van Thiel-de, Ruiter, GCF, Wilson, JHP, Knook, DL, Brouwer A (1991) Chronic administration of ethanol with high vitamin A supplements in a liquid diet to rats does not cause liver fibrosis. J Hepatol 13, 249–255.CrossRefGoogle Scholar
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
Smith, JE, Lawless, DC, Green, MH & Moon, RC (1992) Secretion of vitamin A and retinol-binding protein into plasma is depressed in rats by N-(4-hydroxyphenyl)retinamide (Fenretinide). J Nutr 122, 1999–2009.CrossRefGoogle Scholar
Sporn, MB, Roberts, AB & Goodman, DWS (1984) The Retinoids, 1st ed. London: Academic Press.Google ScholarPubMed
Tateishi, T, Kumai, K, Watanabe, M, Tanaka, M & Kobayashi, S (1999) A comparison of the effect of five phenothiazines on hepatic CYP isozymes in rats. Pharmacol Toxicol 85, 252–256.CrossRefGoogle ScholarPubMed
Thomas, PE, Reik, LM, Ryan, DE & Levin, W (1983) Induction of two immunochemically related rat liver cytochrome P-450 isozymes, cytochromes P-450c and P-450d, by structurally diverse xenobiotics. J Biol Chem 258, 4590–4598.CrossRefGoogle ScholarPubMed
Thompson, JN, Erdody, P, Brien, R & Murray, TK (1971) Fluorometric determination of vitamin A in human blood and liver. Biochem Med 5, 67–89.CrossRefGoogle Scholar
Tuitoek, PJ, Lakey, JRT, Rajotte, RV & Basu, TK (1996) Strain variation in vitamin A (retinol) status of streptozotocin-induced diabetic rats. Int J Vitam Nutr Res 66, 101–105.Google ScholarPubMed
Vannucchi, MIT, Vannucchi, H & Humphreys, M (1992) Serum levels of vitamin A and retinol binding protein in chronic renal patients treated by continuous ambulatorial peritoneal dialysis. Int J Vitam Nutr Res 62, 107–112.Google ScholarPubMed
Werb, R, Clark, WF, Lindsay, RM, Jones, EOP & Linton, AL (1979) Serum vitamin A levels and associated abnormalities in patients on regular dialysis treatment. Clin Nephrol 12, 63–68.Google ScholarPubMed