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 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.
Shin
M
M
School of Pharmacy, Kobe Gakuin University, Japan.
Asada
S
S
Mizumori
N
N
Sano
K
K
Umezawa
C
C
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology*; D002994:Clofibrate / Q000493:pharmacokinetics*; D000960:Hypolipidemic Agents / Q000493:pharmacokinetics*; D008099:Liver / Q000201:enzymology*; D008297:Male; D009243:NAD / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013881:Thioridazine / Q000494:pharmacology*
D014150:Antipsychotic Agents; D000960:Hypolipidemic Agents; D009243:NAD; D002994:Clofibrate; D013881:Thioridazine; D002746:Chlorpromazine