Studies on Oxidized Starch Sulfates for Medical Purposes

VI. Clearing Activity, Hypocholesteremic Action, and Inhibition of Experimental Atherosclerosis of Oxidized Starch Sulfates

Abstract

After synthesizing Oxidized Starch Sulfates (OS-S) with various chemical properties (molecular weight and sulfur content), investigations were made on the relationships between chemical properties of OS-S and their several biological properties in order to use them for medical purposes such as hypercholesteremia and atherosclerosis.
Outlines of the experimental methods used and the conclusions obtained were as follows. Clearing activity: In order to demonstrate the different behaviours of clearing activity induced by heparin or OS-S, samples were administered intravenously to rabbits and blood samples were drawed repeatedly at appropriate time intervals to analyze clearing activity.
The lipemia clearing activity of OS-S was then compared with that of heparin and it was observed that maximal activation of clearing activity by OS-S occurred within 60 to 90 minutes after administration and duration of the activity was prolonged while the maximum was reached within 15 to 30 minutes and the activity declined rapidly in the case of heparin.
Relationships between the clearing activity of OS-S and molecular weight (viscosity) or degree of sulfation of it was studied. It was recognized that the lipemia clearing activity of OS-S was parallel with their sulfur content but not with molecular weight (viscosity). It was also revealed that there was no direct correlation between clearing activity and blood anticoagulant activity of OS-S.
Hypocholesteremic aciton: Hypocholesteremic action of the OS-S which has strong clearing activity, was examined using hypercholesteremic rabbits. It was observed that OS-S reduced turbidity and serum total cholesterol significantly and this hypocholesteremic action of OS-S was more effective than that of heparin. Since the peak of the decrease of cholesterol occurred slower than that of turbidity, it was considered that the decrease of the former was induced indirectly by clearing factor which hydrolyzes the triglycerides in β-lipoprotein and produced umballance in β-lipoprotein.
Inhibition of Atherosclerosis: Simultaneously with the beginning of cholesterol feeding the treatment of these animals with 5mg/kg of OS-S (sulfur content 16.00, [η] 0.0078) twice daily was begun and continued for fifty days. OS-S prevented significantly the rises of serum turbidity and serum total cholesterol. The values of serum turbidity and cholesterol treated with OS-S were less than half of the values untreated controls at the end of the experiment.
OS-S also inhibited the development of atherosclerosis as judged by naked eyes. The average aorta of the animals treated with OS-S presented less than one sixth the atheroma area of the untreated control aorta. The differences between the mean blood clotting time of the rabbits treated with OS-S and untreated control were not significant.
From the above experiments it is concluded that OS-S which have sulfur content ranging from 13 to 16% and molecular weight about 3, 000 are suitable for clearing action of hyperlipemia, hypocholesteremic action, and inhibition of atherosclerosis.