Mourelle M, Amezcua J L, Pérez-Alvarez V
Eur J Pharmacol. 1987 Feb 10;134(2):175-80. doi: 10.1016/0014-2999(87)90163-4.
We have compared the effects of BW755C, a dual inhibitor of the arachidonic acid cyclo-oxygenase and lipoxygenase, with the effects of colchicine and indomethacin on the reversion of the biochemical and histochemical signs of rat liver cirrhosis. This was induced by i.p. administration of CCl4 for 11 weeks. At this point the rats were divided into four groups (10 animals each). CCl4 administration was continued for one month along with either colchicine, BW755C or indomethacin. No additional treatment was given to the control group. BW755C consistently improved all the parameters studied. Although colchicine also improved all but two markers (serum ALT activity and serum proteins) it ranked lower than BW755C in most of them. Indomethacin only modified favourably serum alkaline phosphatase activity, serum proteins, cholesterol and bilirubins and liver collagen content. The effects of BW755C could be mainly attributed to the inhibition of the lipoxygenase pathway. A common feature of colchicine, adrenal steroids and BW755C was the ability to inhibit the formation of leukotriene and other lipoxygenase products. The possibility that this property might contribute to their anti-cirrhotic actions is discussed.
我们比较了花生四烯酸环氧化酶和脂氧化酶的双重抑制剂BW755C、秋水仙碱和吲哚美辛对大鼠肝硬化生化及组织化学指标逆转的影响。肝硬化是通过腹腔注射四氯化碳11周诱导而成。此时将大鼠分为四组（每组10只动物）。四氯化碳给药持续一个月，同时分别给予秋水仙碱、BW755C或吲哚美辛。对照组不给予额外治疗。BW755C持续改善了所有研究参数。虽然秋水仙碱也改善了除两项指标（血清谷丙转氨酶活性和血清蛋白）外的所有指标，但在大多数指标上其排名低于BW755C。吲哚美辛仅对血清碱性磷酸酶活性、血清蛋白、胆固醇、胆红素及肝脏胶原含量有有利影响。BW755C的作用可能主要归因于对脂氧化酶途径的抑制。秋水仙碱、肾上腺皮质类固醇和BW755C的一个共同特点是能够抑制白三烯和其他脂氧化酶产物的形成。本文讨论了这一特性可能有助于它们的抗肝硬化作用的可能性。
