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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]
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Abstract

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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

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