Effect of thioridazine or chlorpromazine on increased hepatic NAD(+) levelin rats fed clofibrate, a hypolipidaemic drug

The effect of the phenothiazines, thioridazine and chlorpromazine, on the i ncreased hepatic NAD(+) level of rats fed clofibrate, a hypolipidaemic drug , has been investigated. Short-term (6 days) addition of phenothiazines to the diet negatively affec ted diet intake and body-weight gain, but increased liver weight and hepati c NAD+ levels, which was synergistic to clofibrate. The phenothiazines were shown to inhibit hepatic peroxisomal fatty acid oxidation in-vivo, as dete rmined by the increased residual catalase activity. In hepatocytes prepared from clofibrate-fed rats, phenothiazines inhibited not only peroxisomal bu t also mitochondrial fatty acid oxidation to the same extent. In the hepato cytes, NAD(+) was maintained at the high level until the phenothiazine conc entration was increased to 0.2 mM. The result suggests that the increase of hepatic NAD(+) in rats fed clofibr ate is not related to peroxisomal fatty acid oxidation.