Facultad de Ciencias Experimentales y Técnicas, Universidad San Pablo-CEU, P.O. Box 67, 28660 Boadilla del Monte, Madrid, Spain.
Environ Toxicol Pharmacol. 1998 Aug 4;6(1):59-66. doi: 10.1016/s1382-6689(98)00020-9.
In vitro effects of pantethine on adipose tissue lipolysis and on both hepatic and intestinal cholesterol and fatty acid synthesis in normolipidemic rats are determined and related to their respective in vivo hypolipidemic effects after acute oral administration. At 3, 5, 7 and 24 h after a single high dose of pantethine to rats, free fatty acids (FFA), cholesterol and triglycerides levels decreased whereas plasma glycerol increased, the effect becoming significant at 7 h. The release of glycerol and FFA by epididymal fat pad pieces from rats was measured in Krebs Ringer bicarbonate-albumin buffer supplemented or not with epinephrine and several concentrations of pantethine (0, 10(-5), 10(-4), or 10(-3) M), and it turned out to be enhanced as pantethine concentration increased. Besides, when glucose was present in the medium, this drug lowered fatty acid re-esterification in a dose-dependent manner, the effect being specially evident in the presence of epinephrine. In vitro synthesis of both cholesterol and fatty acids by slices of liver or intestinal epithelial cells was depressed as the concentration of pantethine increased in the medium. Thus, an inhibition of both cholesterolgenesis and lipogenesis seems to contribute to the hypocholesterolemic and hypotriglyceridemic effects of pantethine. On the other hand, the stimulation of lipolysis and the inhibition of fatty acid re-esterification on adipose tissue caused by pantethine must be counteracted by a high fatty acid oxidation in the liver which would explain the decrease in FFA and the increase in glycerol levels detected in the plasma of the pantethine-treated animals.
在正常脂质的大鼠中，测定了泛硫乙胺对脂肪组织脂解作用以及对肝脏和肠道胆固醇和脂肪酸合成的体外影响，并将其与急性口服后的各自体内降血脂作用相关联。在大鼠单次给予高剂量泛硫乙胺后 3、5、7 和 24 小时，游离脂肪酸（FFA）、胆固醇和甘油三酯水平降低，而血浆甘油增加，7 小时后作用变得显著。在补充或不补充肾上腺素和几种浓度的泛硫乙胺（0、10(-5)、10(-4)或 10(-3)M）的 Krebs-Ringer 碳酸氢盐-白蛋白缓冲液中，测量来自大鼠附睾脂肪垫的甘油和 FFA 的释放，结果表明随着泛硫乙胺浓度的增加而增强。此外，当培养基中存在葡萄糖时，该药物以剂量依赖的方式降低脂肪酸再酯化，在存在肾上腺素的情况下，这种作用特别明显。当培养基中泛硫乙胺浓度增加时，肝脏或肠上皮细胞的胆固醇和脂肪酸的体外合成受到抑制。因此，胆固醇生成和脂肪生成的抑制似乎有助于泛硫乙胺的降胆固醇和降甘油三酯作用。另一方面，泛硫乙胺引起的脂肪组织脂解的刺激和脂肪酸再酯化的抑制必须被肝脏中的高脂肪酸氧化所抵消，这可以解释在泛硫乙胺处理的动物的血浆中检测到的 FFA 减少和甘油水平增加。
