Study of te Pharmacological Effect of the Bile Salt, Sodium Scymnol Sulfate, from Phizoprionodon acutus. III. Protective Effect of Scymnol against Vascular Endothelial Cell Damage in a Rat Peripheral Arterial Occlusion Model

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The prophylactic action of scymnol in a rat peripheral arterial occlusion model, involving injection of 5% lactic acid into the femoral artery, was investigated. Increases in serum lactate dehydrogenase (LDH), glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities and in plasma levels of thrombin and antithrombin III complex (TAT) were observed in this model 3 h after injection of lactic acid. Changes in LDH activity were characterized by increases in isozymes LDH_4 and LDH_5 and an elevated LDH_4/LDH_5 ratio. The ratio of the LDH_4 to LDH_5 increments was similar to that seen in a rat endothelial cell culture.Oral preadministration of scymnol had a preventive effect on the development of lesions in this model. It significantly reduced the LDH_4 and LDH_5 activity, the LDH_4/LDH_5 ratio and the TAT levels dose-dependently over the range 1,3 or 10 mg/kg, compared with the values in control rats. However, its administration after lactic acid injection, or to sham-operated rats was ineffective, even at a dose of 10 mg/kg. The effects of scymnol were also compared with those of ticlopidine and argatroban.The findings show that scymnol may be useful in preventing thrombotic peripheral arterial occlusive disorders and that it potently protects endothelial cells against lactic acidosis in this model.
公益社団法人日本薬学会の論文
1999-08-15