Tuberc Respir Dis.  2011 May;70(5):390-396.

The Effect of Hyaluronan Treatment in Endotoxemic Rats

• Rho BH
• Kwon KY
• Choi WI

Abstract

BACKGROUND
Hyaluronan (HA) is an unbranched glycosaminoglycan. It has been proposed that HA acts as a vehicle for cytokines due to the strong negative charge on its surface. We hypothesized that HA would function like a cytokine scavenger and reduce the inflammatory signaling cascade and this would lead to improved survival in rats suffering with endotoxemia.
METHODS
Endotoxin (Salmonella, 10 mg/kg) or an equal amount of 0.9% NaCl (NS) was injected into the jugular vein of rats. HA (1,600 kDa, 0.35%) or NS was given at 0.1 mL/kg/h for 3 hours. HA or NS infusion was started at 4 hour after endotoxin injection. The rats were divided into the control and HA groups (n=16 for each group). The mean arterial pressure (MAP) was monitored during HA or normal saline infusion. Survival was assessed every 12 hours for 3 days throughout the experiment.
RESULTS
The survival rate (%) of the rats treated with HA was higher (60%) than that of the controls (20%) when HA was infused 4 hours after lipopolysaccharide (LPS) injection. The bronchoalveolar lavage (BAL) fluid of the animals surviving HA or NS infusion 4 hours after LPS showed that the total cell counts and number of neutrophils were significantly (p<0.01) reduced in the HA treated groups compared with that of the controls (total cell count, 9.2x10(4)/mL vs. 61x10(4)/mL; neutrophils, 21x10(4)/mL vs. 0.2x10(4)/mL, respectively). There was no significant MAP difference between the HA or control groups either with or without endotoxin.
CONCLUSION
Infusion of hyaluronan (1,600 kDa) reduced the BAL total cell count and the number of neutrophils and it improved the survival rate of the endotoxemic rats.

Keyword

Endotoxemia; Hyaluronic Acid; Survival

MeSH Terms

Animals
Arterial Pressure
Bronchoalveolar Lavage
Cell Count
Cytokines
Endotoxemia
Fees and Charges
Hyaluronic Acid
Jugular Veins
Neutrophils
Rats
Stress, Psychological
Survival Rate
Cytokines
Hyaluronic Acid

Figure

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  Figure 1 Intravenous infusion of hyaluronan (LPS+HA) in endotoxemic rats prolonged the animals' survival compared with that of the saline control (LPS+Saline) (n=16 per group). LPS: lipopolysaccharide; HA: hyaluronan.

• 

  Figure 2 Representative histology findings (hematoxylin and eosin stain, original magnification, ×100). The lungs were removed after three hours of infusion of hyaluroan or 0.9% NaCl in the endotoxemic rats. (A) Control, (B) LPS+0.9% NaCl, (C) LPS+Hyaluronan (1,600 kDa). LPS: lipopolysaccharide.

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  Figure 3 Treatment with hyaluronan (HA) significantly reduced the total number of cells (A) and neutrophils (B) in the bronchoalveolar lavage fluid (n=7 rats per group). *p<0.01 LPS+NS vs. LPS+HA at 7 hours. LPS: lipopolysaccharide; NS: NaCl; HA: hyaluronan.

• 

  Figure 4 The levels of serum tumor necrosis factor-α (TNF-α) (A), interleukin-10 (IL-10) (B), interleukin-6 (IL-6) (C) and macrophage inflammatory protein-2 (MIP-2) (D) were measured at baseline, 4-, 7- and 72 hour after endotoxemia. Treatment with hyaluronan (HA) significantly reduced the serum levels of TNF-α and MIP at 7 h after endotoxemia compared with that of the control (n=7 rats per group). *p<0.01 LPS+NS vs. LPS+HA at 7 hours. LPS: lipopolysaccharide; NS: NaCl.

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  Figure 5 Effect on the mean arterial pressure (MAP) in rats treated with either hyaluronan (HA) or 0.9% NaCl (NS) one hour after endotoxemia (LPS). Hyaluronan infusion did not cause a significant MAP change in the rats with or without endotoxemia (open triangle=LPS+NS; open circle=LPS+HA; closed triangle=NS; closed circle=HA).

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