Study of the pharmacological effect of the bile salt, sodium scymnol sulfate, from Rhizoprionodon acutus. III. Protective effect of scymnol against vascular endothelial cell damage in a rat peripheral arterial occlusion model

The prophylactic action of scymnol in a rat peripheral arterial occlusion m odel, involving injection of 5% lactic acid into the femoral artery, was in vestigated, Increases in serum lactate dehydrogenase (LDH), glutamic oxaloa cetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities and in plasma levels of thrombin and antithrombin III complex (TAT) were o bserved in this model 3 h after injection of lactic acid. Changes in LDH ac tivity were characterized by increases in isozymes LDH4 and LDH5 and an ele vated LDH4/LDH5 ratio. The ratio of the LDH4 to LDH5 increments was similar to that seen in a rat endothelial cell culture. Oral preadministration of scymnol had a preventive effect on the developmen t of lesions in this model, It significantly reduced the LDH4 and LDH5 acti vity; the LDH4/LDH5 ratio and the TAT levels dose-dependently over the rang e 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 in effective, ev en at a dose of 10 mg/kg. The effects of scymnol were also co mpared with those of ticlopidine and argatroban. The findings show that scymnol may be useful in preventing thrombotic perip heral arterial occlusive disorders and that it potently protects endothelia l cells against lactic acidosis in this model.