Removal Of Hyaluronan Research Articles

Association of galactosamine-induced hepatitis in the rat with hyperhyaluronanaemia and decreased hyaluronan uptake by the isolated, perfused liver

Plasma hyaluronan (HA) concentration and the rate of HA uptake by the isolated, perfused liver were measured in rats treated with saline, D-galactosamine (GaINH 2, 50 mg/100 g body wt), gadolinium chloride (GdCl 3) (0.5 mg/100 g body wt), and GdCl 3 + GaINH 2. GdCl 3 was given 24 hr before GaINH 2 or saline. Plasma L-alanine:2-oxoglutarate aminotransferase (EC 2.6.1.2), a marker for hepatocyte damage, was increased by 8 hr and remained elevated for 24 hr after GaINH 2 injection. GdCl 3 did not affect plasma enzyme levels when given alone or in association with, but prior to, GaINH 2. Plasma HA levels were increased (200%) within 2 hr GaI administration. A plateau was reached at 8 hr, which was maintained for at least 24 hr. Although GdCl 3 alone did not affect plasma HA levels, it slightly delayed the increase in HA concentration in GaINH 2-treated rats. Liver, isolated 24 hr after GaINH 2 treatment, exhibited a severe depression (approximately 67%) of HA uptake. GdCL 3 did not prevent this suppression. The data presented indicate that: (1) one of the sinusoidal endothelial cell-dependent functions of the liver, i.e. removal of HA from the blood stream, is profoundly impaired during galactosamine-induced hepatitis, and (2) the adverse effect of GaINH 2 on this sinusoidal endothelial cell function may not be dependent on GdCl 3-suppressible Kupffer cell functions.

Gram-negative bacterial lipopolysaccharide impairs hyaluronan clearance in vivo and its uptake by the isolated, perfused rat liver

The purpose of this investigation was to examine the effect of gram-negative bacterial lipopolysaccharide on hyaluronan concentration in blood plasma, hyaluronan removal from the blood and hyaluronan uptake by isolated, perfused rat liver. Intravenous administration of Escherichia coli lipopolysaccharide to rats markedly increased plasma hyaluronan concentration in a dose-dependent manner. One day after lipopolysaccharide challenge (0.1 or 1.0 mg per 100 gm body wt), plasma hyaluronan levels were 570.7 +/- 66.8 ng x ml-1 and 1,951.0 +/- 120.3 ng x ml-1, respectively, as compared with 94.2 +/- 12.2 ng x ml-1 in the time-matched control animals. Removal of intravenously injected hyaluronan (30 micrograms per 100 gm body wt) was suppressed 32% by lipopolysaccharide administration (100 micrograms per 100 gm body wt). At the same dose, lipopolysaccharide induced a severe inhibition (60% to 80%) of hyaluronan uptake by perfused livers isolated 3 or 24 hr after lipopolysaccharide administration. The inhibitory effect of lipopolysaccharide on hyaluronan uptake by the isolated, perfused liver was not abolished by pretreatment with either antibodies to tumor necrosis factor-alpha IgG or indomethacin, an inhibitor of the cyclooxygenase pathway. Continuous intravenous infusion of recombinant murine tumor necrosis factor-alpha for 18 to 20 hr did not affect plasma hyaluronan concentration. These data suggest that neither tumor necrosis factor-alpha, an early cytokine induced by lipopolysaccharide, nor prostaglandins are involved in the mechanism of lipopolysaccharide-induced inhibition of hyaluronan uptake by the perfused rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Disappearance of concentrated hyaluronan from the anterior chamber of monkey eyes

The removal of hyaluronan (HYA) from the primate eye has received attention due to the use of the polymer in ophthalmic surgery. The turnover of concentrated HYA injected into the anterior chamber of 12 cynomolgus monkeys was therefore studied using a technique earlier described for rabbits. The technique is based on the observation that when HYA labelled with tritium in the acetyl group leaves the eye and enters the circulation it is rapidly taken up by the liver and degraded to tritiated water. A mixture of tritium-labelled HYA and high concentration, high molecular weight HYA (Healon R) was injected in amounts of 50 μl (or 75 μl, for three monkeys) into the anterior chamber. The concentration of tritiated water in blood plasma was followed for up to 3 weeks. An initial rise of radioactivity in blood was followed by an exponential decrease, representing the turnover of water in the body. The initial rise of tritium could be corrected for water losses and thereafter corresponded to the disappearance of HYA from the eye, plus a 45-min time lag due to the catabolism in the liver. Using this technique it was found that half of the material had left the anterior chamber after 20 hr when 50 μl (or 75 μl) were injected. Four animals were treated with pilocarpine topically during the first day and the corresponding time was then 8·5 hr. Maximal IOP occurred about 6 and 3 hr after the injection for non-treated and pilocarpine treated animals, respectively.

Disappearance of concentrated hyaluronan from the anterior chamber of monkey eyes

Abstract The removal of hyaluronan (HYA) from the primate eye has received attention due to the use of the polymer in ophthalmic surgery. The turnover of concentrated HYA injected into the anterior chamber of 12 cynomolgus monkeys was therefore studied using a technique earlier described for rabbits. The technique is based on the observation that when HYA labelled with tritium in the acetyl group leaves the eye and enters the circulation it is rapidly taken up by the liver and degraded to tritiated water. A mixture of tritium-labelled HYA and high concentration, high molecular weight HYA (HealonR) was injected in amounts of 50 μl (or 75 μl, for three monkeys) into the anterior chamber. The concentration of tritiated water in blood plasma was followed for up to 3 weeks. An initial rise of radioactivity in blood was followed by an exponential decrease, representing the turnover of water in the body. The initial rise of tritium could be corrected for water losses and thereafter corresponded to the disappearance of HYA from the eye, plus a 45-min time lag due to the catabolism in the liver. Using this technique it was found that half of the material had left the anterior chamber after 20 hr when 50 μl (or 75 μl) were injected. Four animals were treated with pilocarpine topically during the first day and the corresponding time was then 8·5 hr. Maximal IOP occurred about 6 and 3 hr after the injection for non-treated and pilocarpine treated animals, respectively.