Shin M, Asada S, Mizumori N, Sano K, Umezawa C
School of Pharmacy, Kobe Gakuin University, Japan.
J Pharm Pharmacol. 1998 Apr;50(4):431-6. doi: 10.1111/j.2042-7158.1998.tb06884.x.
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.
已对吩噻嗪类药物硫利达嗪和氯丙嗪对喂食降血脂药物氯贝丁酯的大鼠肝脏中烟酰胺腺嘌呤二核苷酸（NAD⁺）水平升高的影响进行了研究。在饮食中短期（6天）添加吩噻嗪类药物对饮食摄入量和体重增加有负面影响，但增加了肝脏重量和肝脏NAD⁺水平，这与氯贝丁酯具有协同作用。通过过氧化氢酶残留活性增加测定表明，吩噻嗪类药物在体内可抑制肝脏过氧化物酶体脂肪酸氧化。在由喂食氯贝丁酯的大鼠制备的肝细胞中，吩噻嗪类药物不仅同等程度地抑制过氧化物酶体脂肪酸氧化，也抑制线粒体脂肪酸氧化。在肝细胞中，直到吩噻嗪类药物浓度增加到0.2 mM时，NAD⁺才维持在高水平。该结果表明，喂食氯贝丁酯的大鼠肝脏中NAD⁺的增加与过氧化物酶体脂肪酸氧化无关。
