Effects of low molecular weight chondroitin sulfate on type II collagen-induced arthritis in DBA/1J mice.
In order to evaluate the improvement in the treatment of chronic arthritis, we investigated chondroitin sulfate depolymerization product (low molecular weight chondroitin sulfate, LMWCS) and intact chondroitin sulfate (CS) in vitro and in vivo. LMWCS was prepared by a chemical depolymerization process induced by hydrogen peroxide in the presence of copper salts. LMWCS (300 mg/kg) and CS (1200 mg/kg) were orally administered to DBA/1J mice once daily for 14 d prior to initial immunization with type II collagen. Their elastase activities and the production of cytokines in sera were examined on type II collagen-induced arthritis in DBA/1J mice. We also compared the paracellular transport of LMWCS and CS across Caco-2 cell monolayers and examined the inhibitory effects on elastase activities. LMWCS inhibited elastase activity slightly, but CS did not show inhibition. Hind paw edema was significantly decreased by LMWCS treatment. Levels of anti-type II collagen antibody and tumor necrosis factor-alpha (TNF-alpha) in sera were also reduced by LMWCS treatment but not in case of CS, although no significant difference was observed between LMWCS and CS on interleukin-6 (IL-6) induction. The LMWCS preparation showed preventive effects on the type II collagen-induced arthritis in DBA/1J mice and better permeability through Caco-2 cells.
Cho
So Yean
SY
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 110-460, Korea.
Sim
Joon-Soo
JS
Jeong
Choon Sik
CS
Chang
Seung Yeup
SY
Choi
Don Woong
DW
Toida
Toshihiko
T
Kim
Yeong Shik
YS
D000818:Animals; D000906:Antibodies / Q000032:analysis; D001168:Arthritis / Q000139:chemically induced* / Q000517:prevention & control*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D002809:Chondroitin Sulfates / Q000032:analysis / Q000138:chemical synthesis / Q000494:pharmacology*; D024043:Collagen Type II / Q000276:immunology; D004187:Disaccharides / Q000032:analysis; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008970:Molecular Weight
D000906:Antibodies; D024043:Collagen Type II; D004187:Disaccharides; D002809:Chondroitin Sulfates; D019272:Leukocyte Elastase