Effect of Alginic Acid on Experimentally Induced Arthropathy in Rabbit Model

토끼의 관절병증에 미치는 알긴산올리고당의 치료효과

  • Accepted : 2002.04.30
  • Published : 2002.06.29


For the induction of arthropathy, 5% hydrogen peroxide($H_2O_2$) was injected for 5 weeks into the intraarticular space of the New Zealand white rabbits to damage articular cartilage. Alginic acid of low molecular weight (2%) made from macromolecular alginate treated with enzyme was administered into articular space at the dose of 5 mg/kg twice a week for 3 and 6 weeks using 1 ml syringe and 26 G needle. Saline was injected for the control. Tissues surrounding the articulation were obtained for the measurements of superoxide dismutase(SOD) activity as a major antioxidant enzyme and malondialdehyde (MDA) as a lipid peroxidation level. Histopathologic examination on the surface of articular cartilage was carried out. Data showed that injection of hydrogen peroxide for 5 weeks had led to the induction of free radical damage and of articular cartilage change as confirmed by microscopic observation. The application of hydrogen peroxide caused a gradual increase in the SODs and MDA. These patterns were similar after 3 and 6 weeks of alginate treatment. Furthermore, microscopic examinations revealed that hydrogen peroxide caused flaking, fibrillation, fissuring, denudation, and hypocellularity in the articular surfaces. In conclusion, lipid peroxidation was demonstrated in the articular cartilage by the administration of hydrogen peroxide in the rabbit model. This lipid peroxidation could be caused by oxygen free radicals. The histologic and enzymatic correlations on lipid peroxidation in the articulation have provided a better understanding of arthropathy. It is possible to take advantage of these findings to evaluate effective alginate dosage more efficiently.


  1. Abatangelo G, Botti P, Del Bue M. Gei G, Samson JC, Cortivo R, De Galateo A, Martelli M. lntraarticular sodium hyaluionate injection in the Pond-Nuki experimental model of osteoarthritis in dogs. I. Biochemical results. Clin Orthop, 241:278-285, 1989
  2. Mitrovic DR, Garcia F, Front P, Guillermet V. Histochemical and cellular changes induced in the rabbit knee joint by an intraarticular implantation of a sheet of polyethylene. Lab Invest, 53:228-239, 1985
  3. Minns, R. J. Steven, F. S. Haidinge, K. Osteoarthrotic articular cartilage lesions of the femoral head observed in the scanning electron nncioscope. J Pathol, 122:63-70, 1977
  4. Walker ER, Boyd RD, Wu DD, Lukoschek M, Burr DB, Radin EL. Morphologic and morphometric changes in synovial membrane associated with rnechanically induced osteoarthrosis. Arthritis Rheum, 34:515-524, 1991
  5. van Valburg AA, van Roermund PM, Marijnissen AC, Wenting MJ, Verbout AJ, Lafeber FP, Bijlsma JW. Joint distiaction in tneatment of osteoarthritis (II): effects on cartilage in a canine model. Osteoarthritis Cartilaee, 8:1-8, 2000
  6. Videman T, Eronen I, Candolin T. [$^3H$]proline incorporation and hydroxyproline concentration in articular cartilage during the development of osteoarthritis caused by immobilization. A study in vivo with rabbits. Biochem J, 200:435-440, 1981
  7. Kim NH, Han CD, Lee HM, Yang IH. Effect of sodium hyaluronate on prevention of osteoarthritis. Yonsei Med J, 32:139-146, 1991
  8. Yoshimi T, Kikuchi T, Obara T, Yamaguchi T, Sakakibara Y, Itoh H, Iwata H, Miura T. Effects of high-molecular-wight sodium hyaluronate on experimental osteoarthrosis induced by the resection of rabbit anterior cruciate ligament. Clin Orthop, 298:296-304, 1994
  9. Bentley G. Papain-induced degenerative arthritis of the hip in rabbits. J Bone Joint Surg Br, 53:324-337, 1971
  10. Tsai CL, Liu TK. Inhibition of estiadiol-induced early osteoarthritic changes by tamoxifen. Life Sci, 50:1943-1951, 1992
  11. Kikuchi T, Sakuta T, Yamaguchi T. Intra-articular injection of collagenase induces experimental osteoarthritis in mature rabbits. Osteoarthritis Cartilage, 6:177-186, 1998
  12. Kaiki G, Tsuji H, Yonezawa T, Sekido H, Takano T, Yamashita S, Hirano N, Sano A. Osteoarthrosis induced by intra-articular hydrogen peroxide injection and running load. J Orthop Res, 8:731-740, 1990
  13. Yutaka N, Sato T, Nishi Y, Takeuch T, Muiata K, Kusakabe I. Purification and characterization of extracellular alginate lyase from Enterobacter cloacae M-l. Biosci Biotech Biochem, 59:632-637, 1995
  14. McCord JM, Fridovich I. Superoxide dismutase: an enzymatic function for erythtocuprein (hemocuprein). J Biol Chem, 244:6049-6055, 1969
  15. Okawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95:351-358, 1979
  16. Hutadilok N, Smith MM, Ghosh P. Effects of hydiogen peroxide on the metabolism of human rheumatoid and osteoarthritic synovial fibroblasts in vitro. Ann Rheum Dis, 50:219-226, 1991
  17. Chrisman OD, Ladenbauer-Bellis IM. Panjabi M, Goeltz S. The relationship of mechanical trauma and the early biochemical reactions of osteoarthritic cartilage. Clin Orthop. 161:275-284, 1981