Effect of Thioridazine or Chlorpromazine on Increased Hepatic NAD+ Level in Rats Fed Clofibrate, a Hypolipidaemic Drug

The effect of the phenothiazines, thioridazine and chlorpromazine, on the increased hepatic NAD+ level of rats fed clofibrate, a hypolipidaemic drug, has been investigated. Short‐term (6 days) addition of phenothiazines to the diet negatively affected diet intake and body‐weight gain, but increased...

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Published in:	Journal of pharmacy and pharmacology Vol. 50; no. 4; pp. 431 - 436
Main Authors:	SHIN, MARIKO, ASADA, SUMIYO, MIZUMORI, NANAE, SANO, KEIJI, UMEZAWA, CHISAE
Format:	Journal Article Conference Proceeding
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-04-1998 Pharmaceutical Press
Subjects:	Animals Antipsychotic Agents - pharmacology Biological and medical sciences Chlorpromazine - pharmacology Clofibrate - pharmacokinetics General and cellular metabolism. Vitamins Hypolipidemic Agents - pharmacokinetics Liver - enzymology Male Medical sciences NAD - metabolism Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Thioridazine - pharmacology Drug combination Rat Clofibrate Fibrate derivatives Liver Rodentia Lipids Phenothiazine derivatives Metabolism Fatty acids Chlorpromazine NAD Vertebrata Mammalia Thioridazine Animal Peroxisome Drug interaction Oxidation Mechanism of action Antilipemic agent
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Summary:	The effect of the phenothiazines, thioridazine and chlorpromazine, on the increased hepatic NAD+ level of rats fed clofibrate, a hypolipidaemic drug, has been investigated. Short‐term (6 days) addition of phenothiazines to the diet negatively affected diet intake and body‐weight gain, but increased liver weight and hepatic NAD+ levels, which was synergistic to clofibrate. The phenothiazines were shown to inhibit hepatic peroxisomal fatty acid oxidation in‐vivo, as determined by the increased residual catalase activity. In hepatocytes prepared from clofibrate‐fed rats, phenothiazines inhibited not only peroxisomal but also mitochondrial fatty acid oxidation to the same extent. In the hepatocytes, NAD+ was maintained at the high level until the phenothiazine concentration was increased to 0–2 mM. The result suggests that the increase of hepatic NAD+ in rats fed Clofibrate is not related to peroxisomal fatty acid oxidation.
Bibliography:	ArticleID:JPHP6884 ark:/67375/WNG-Z0K6WZR2-N istex:2CC06FAB1B8F8BBF34B379FFDD2CA1F0639161E0 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3573 2042-7158
DOI:	10.1111/j.2042-7158.1998.tb06884.x