Physico-chemical properties and the structure of dermatan sulfate fractions purified from plasma after oral administration in healthy human volunteers.
Dermatan sulfate (DS) was administered by oral route in healthy human volunteers. The structure, physico-chemical properties and biological activity of DS purified from human plasma after oral administration were studied and compared with those of native DS. DS extracted and purified from pig mucosa has a relative molecular mass (Mr) of about 23,100 and is composed of about 10% nonsulfated disaccharide, 80% monosulfated disaccharides and about 10% disulfated disaccharides, with a sulfate to carboxyl ratio of 1.00 and a heparin cofactor II (HCII) activity of about 160 units/mg. This native polysaccharide is composed of about 94% iduronic acid. One gram of native DS was orally administered to five healthy human volunteers, and 50 ml of blood were collected after 4 h. DS possibly present in plasma after oral administration was extracted and purified. About 130 +/- 42 micrograms of DS per 50 ml of blood were detected by agarose-gel electrophoresis and DMB assay. This DS shows a broad Mr range. After oral absorption, substantial amounts of species with a Mr of about 7,500 are detected in blood but chains with Mr ranging from 7,500 to 20,000 are also found. Moreover, some very low-Mr species are detected, with a prevalence of disaccharides. After oral absorption, DS is sulfated above all in position 4 of the N-acetyl-galactosamine (60%), with a sulfate to carboxyl ratio of about 0.64, demonstrating that DS is desulfated during or after oral absorption by about 30-40%, A small amount of disulfated disaccharide (in particular 2,4-disulfated, 1.4%) is preserved from catabolic processes, as DS extracted from human plasma is able to inhibit thrombin activity mediated by HCII (about 16 U/mg).
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Department of Biologia Animale, University of Modena, Italy.
D000328:Adult; D000818:Animals; D002240:Carbohydrate Sequence; D005591:Chemical Fractionation; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003871:Dermatan Sulfate / Q000097:blood / Q000737:chemistry* / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015394:Molecular Structure; D008970:Molecular Weight; D012016:Reference Values; D013552:Swine
D003871:Dermatan Sulfate