Mourelle M, Amezcua J L, Hong E
Pharmacology and Toxicology Department, Centro de Investigación y de Estudios Avanzados del, I.P.N., México, D.F.
Prostaglandins. 1987 Jun;33(6):869-77. doi: 10.1016/0090-6980(87)90115-8.
The effects of colchicine (10 g/day p.o. for 7 days) and rioprostil (2-decarboxy, 2-hydroxymethyl-15-deoxy-16-RS-hydroxy-16-methyl-prostaglandin-E1) (20 g/kg s.c., a single dose) on the enzymatic and histological markers of acute liver damage were studied in rats intoxicated with a single oral dose of CCl4. The rats were sacrificed 24 h after CCl4. The lipid composition of the liver plasma membranes was also determined. The increase in Alk. Phosp., GGTP and GPT activities and bilirubin concentration in serum as well as the histological images produced by CCl4 were equally prevented by the treatments with colchicine or rioprostil. CCl4 changed the lipid composition of the liver plasma membrane by increasing PI and PC and decreasing SM, PS and PEA. There was a decrease in the cholesterol/phospholipid ratio at the expense of a reduction of cholesterol/protein ratio and elevation in phospholipid/protein ratio. Colchicine and rioprostil also prevented these lipid alterations. The results suggest that the plasma membrane is an important site of action of CCl4 and of the 2 drugs studied. We postulate that the plasma membrane rather than other organelles is the target for the cytoprotective actions of prostaglandins.
研究了秋水仙碱（口服，10克/天，持续7天）和利奥前列素（2-脱羧基，2-羟甲基-15-脱氧-16-RS-羟基-16-甲基-前列腺素-E1）（皮下注射，20微克/千克，单次剂量）对单次口服四氯化碳中毒大鼠急性肝损伤的酶学和组织学标志物的影响。在给予四氯化碳24小时后处死大鼠。还测定了肝细胞膜的脂质组成。秋水仙碱或利奥前列素处理同样能阻止血清中碱性磷酸酶、γ-谷氨酰转肽酶和谷丙转氨酶活性以及胆红素浓度的升高，以及四氯化碳所致的组织学图像改变。四氯化碳通过增加磷脂酰肌醇和磷脂酰胆碱以及减少鞘磷脂、磷脂酰丝氨酸和磷脂酰乙醇胺来改变肝细胞膜的脂质组成。胆固醇/磷脂比值降低，同时胆固醇/蛋白质比值降低，磷脂/蛋白质比值升高。秋水仙碱和利奥前列素也能阻止这些脂质改变。结果表明，细胞膜是四氯化碳和所研究的两种药物的重要作用部位。我们推测，细胞膜而非其他细胞器是前列腺素细胞保护作用的靶点。
