Plasma clearance, tissue distribution and metabolism of hyaluronic acid injected intravenously in the rabbit

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Abstract
The plasma clearance, tissue distribution and metabolism of hyaluronic acid were studied with a high average MW. [3H]acetyl-labeled hyaluronic acid synthesized in synovial cell cultures. After i.v. injection in the rabbit, the label disappeared from the plasma with a half-life of 2.5-4.5 min, which corresponds to a normal hyaluronic acid clearance of .apprx. 10 mg/day per kg body wt. Injection of unlabeled hyaluronic acid 15 min after the tracer failed to reverse its absorption. Clearance of labeled polymer was retarded by prior injection of excess unlabeled hylauronic acid. The maximum clearance capacity was estimated in these circumstances to be .apprx. 30 mg/day per kg body wt. The injected material was concentrated in the liver and spleen. As much as 88% of the label was absorbed by the liver, where it was found almost entirely in nonparenchymal cells. Degradation was rapid and complete, since volatile material, presumably 3H2O, appeared in the plasma within 20 min. Undegraded [3H]hyaluronic acid, small labeled residues and 3H2O were detected in the liver, but there was little evidence of intermediate oligosaccharides. No metabolite except 3H2O was recognized in plasma or urine. Two-thirds of the radioactivity was retained in the body water 24 h later and small amounts were found in liver lipids. Radioactivity did not decline in the spleen as rapidly as in the liver. The upper MW limit for renal excretion was .apprx. 25,000. Renal excretion played a negligible part in clearance. Hyaluronic acid is removed from the plasma and degraded quickly by an efficient extrarenal system with a high reserve capacity, sited mainly in the liver.