Singh Y, Liu G A, Krishna G
Section on Drug-Tissue Interaction, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
J Toxicol Environ Health. 1987;22(4):459-69. doi: 10.1080/15287398709531085.
Valproic acid induced a dose-dependent increase in carnitine acetyltransferase (CAT) activity in rat hepatic mitochondrial fractions isolated by differential centrifugation. An increase in CAT and carnitine palmitoyltransferase (CPT) also occurred in cultured rat hepatocytes in a concentration-and time-dependent fashion. A maximal increase of 8-fold in the activity of CAT and 2-fold in the activity of CPT was induced by 3 mM valproic acid in 72 h. Valproic acid had no effect on cytochrome P-450 levels in cultured rat hepatocytes. Electron-microscopic examination of rat hepatocytes showed that there was no increase in the number of peroxisomes but there was a marked proliferation of mitochondria in parallel with an increase in glutathione level and succinic dehydrogenase in the liver cells after incubation with valproic acid in vitro.
通过差速离心分离得到的大鼠肝脏线粒体组分中，丙戊酸可诱导肉碱乙酰转移酶（CAT）活性呈剂量依赖性增加。在培养的大鼠肝细胞中，CAT和肉碱棕榈酰转移酶（CPT）活性也呈浓度和时间依赖性增加。在72小时内，3 mM丙戊酸可使CAT活性最大增加8倍，CPT活性增加2倍。丙戊酸对培养的大鼠肝细胞中细胞色素P-450水平没有影响。对大鼠肝细胞进行电子显微镜检查发现，过氧化物酶体数量没有增加，但在体外与丙戊酸孵育后，肝细胞中线粒体显著增殖，同时谷胱甘肽水平和琥珀酸脱氢酶增加。
