IJCM  Vol.3 No.5 , September 2012
Effect of Colchicine on Total Antioxidant Capacity, Antioxidant Enzymes and Oxidative Stress Markers in Patients with Knee Osteoarthritis
ABSTRACT
Background/Aim: We aimed to investigate the effects of colchicine on clinical recovery, as well as oxidative stress markers and total antioxidant capacity (TAC) in whole blood of patients with knee osteoarthritis (OA). Materials and methods: Sixty patients with grade 2 - 3 knee OA according to ACR knee OA criteria whom examination of the knee joint synovial fluid by polarized light microscopy demonstrated CPDD crystals existence were included in the study. Fifty healthy subjects were included as a control group. Patients were divided randomly into two groups. The first group (paracetamol group) was given only paracetamol 3 gr daily p.o and the second group (colchicine and paracetamol group) was given colchicine 1,5 gr and paracetamol 3 gr daily p.o for six months. For outcome measures WOMAC and VAS were used. Superoxide dismutase (SOD), Catalase (CAT) ezyme activities and Glutathione (GSH) and Malondialdehyde (MDA) levels and TAC all were measured. Results: WOMAC scores were improved in both patient groups compared with pre-treatment evaluation (p < 0.025). WOMAC morning stiffness scores were significantly more improved in colchicine group compared with paracetamol group (p > 0.05). TAC was signifcantly increased only in colchicine/paracetamol group. Oxidant parameter MDA levels were significantly decreased in both paracetamol group and colchicine/paracetamol group. CAT, SOD enzyme activities and GSH levels did not change before and after treatment protocols in both patient groups. Conclusion: Both paracetamol 3000 mg/day and 3000 mg paracetamol plus 1,5 gr/day colchicine is effective in the treatment of patients with knee osteoarthritis. But the addition of colchicine to paracetamol produced significantly greater symptomatic benefit than paracetamol alone. Our study also showed that colchicine lowers whole blood MDA which is a lipid peroxidation compound and elevates TAC levels in patients with knee OA. This may show probable disease modifying effect of colchicine in knee OA which require further long period laboratory and radiologic investigations.

Cite this paper
M. Erden, L. Ediz, Ö. Hız, Y. Tuluce, H. Ozkol, M. Toprak and F. Demirdag, "Effect of Colchicine on Total Antioxidant Capacity, Antioxidant Enzymes and Oxidative Stress Markers in Patients with Knee Osteoarthritis," International Journal of Clinical Medicine, Vol. 3 No. 5, 2012, pp. 377-382. doi: 10.4236/ijcm.2012.35071.
References
[1]   M. B. Goldring and S. R. Goldring, “Osteoarthritis,” Journal of Cellular Physiology, Vol. 213, No. 3, 2007, pp. 626-634. doi:10.1002/jcp.21258

[2]   P. Sarzi-Puttini, M. A. Cimmino, R. Scarpa, R. Caporali, F. Parazzini, A. Zaninelli, F. Atzeni and B. Canesi, “Osteoarthritis: An Overview of the Disease and ?ts Treatment Strategies,” Seminars in Arthritis and Rheumatism, Vol. 35, No. 1, 2005, pp. 1-10.

[3]   Y. Z. Liu, A. P. Jackson and S. D. Cosgrove, “Contribution of Calcium-Containing Crystals to Cartilage Degradation and Synovial ?nflammation in Osteoarthritis,” Osteoarthritis and Cartilage, Vol. 17, No. 10, 2009, pp. 1333-1340.

[4]   K. Jaovisidha and A. K. Rosenthal, “Calcium Crystals in Osteoarthritis,” Current Opinion in Rheumatology, Vol. 14, No. 3, 2002, pp. 298-302.

[5]   H. K. Ea and F. Liote, “Advances in Understanding Calcium-Containing Crystal Disease,” Current Opinion in Rheumatology, Vol. 21, No. 2, 2009, pp. 150-157.

[6]   E. A. Regan, R. P. Bowler and J. D. Crapo, “Joint Fluid Antioxidants Are Decreased in Osteoarthritic Joints Compared to Joints with Macroscropically ?ntact Cartilage and Subacute ?njury,” Osteoarthritis Cartilage, Vol. 16, No. 4, 2008, pp. 515-521.

[7]   O. Altindag, O. Erel, N. Aksoy, S. Selek, H. Celik and M. Karaoglanoglu, “Increased Oxidative Stress and Its Relation with Collagen Metabolism in Knee Osteoarthritis,” Rheumatology International, Vol. 27, No. 4, 2007, pp. 339-344.

[8]   S. Sarban, A. Kocyigit, M. Yazar and U. E. Is?kan, “Plasma Total Antioxidant Capacity, Lipid Peroxidation, and Erythrocyte Antioxidant Enzyme Activities in Patients with Rheumatoid Arthritis and Osteoarthritis,” Clinical Biochemistry, Vol. 38, No. 11, 2005, pp. 981-986. doi:10.1016/j.clinbiochem.2005.08.003

[9]   A. F. Chen, C. M. Davies, M. De Lin and B. Fermor, “Oxidative DNA Damage in Osteoarthritic Porcine Articular Cartilage,” Journal of Cellular Physiology, Vol. 217, No. 3, 2008, pp. 828-833. doi:10.1002/jcp.21562

[10]   C. M. Davies, F. Guilak, J. B. Weinberg and B. Fermor, “Reactive Nitrogen and Oxygen Species in ?nterleukin-1-Mediated DNA Damage Associated with Osteoarthritis,” Osteoarthritis Cartilage, Vol. 16, No. 5, 2008, pp. 624- 630. doi:10.1016/j.joca.2007.09.012

[11]   Y. E. Henrotin and B. Kurz, “Oxygen and Reactive Oxygen Species in Cartilage Degradation: Friends or Foes?” Osteoarthritis Cartilage, Vol. 13, No. 8, 2005, pp. 643- 654.

[12]   J. C. Monboisse and J. P. Borel, “Oxidative Damage to Collagen,” EXS, Vol. 62, 1992, pp. 323-327.

[13]   J. M. McCord, “Free Radicals and ?nflammation: Protection of Synovial Fluid by Superoxide Dismutase,” Science, Vol. 185, No. 150, 1974, pp. 529-531.

[14]   A. Klamfeldt and S. Marklund, “Enhanced Breakdown in Vitro of Bovine Articular Cartilage Proteoglycans by Conditional Synovial Medium: The Effect of Superoxide Dismutase and Catalase,” Scandinavian Journal of Rheumatology, Vol. 16, 1987, pp. 41-45.

[15]   H. Burkhardt, M. Schwingel, H. Menninger, H. W. Macartney and H. Tschesche, “Oxygen Radicals as Effectors of Cartilage Destruction: Direct Degradative Effect on Matrix Components and ?ndirect Action via Activation of Latent Collagenase from Polymorphonuclear Leukocytes,” Arthritis & Rheumatism, Vol. 29, 1986, pp. 379-387. doi:10.1002/art.1780290311

[16]   H. M. Lander, A. J. Milbank, J. M. Tauras, D. P. Hajjar, B. L. Hempstead, G. D. Schwartz, et al., “Redox Regulation of Cell Signalling,” Nature, Vol. 381, 1996, pp. 380-381. doi:10.1038/381380a0

[17]   R. H. Burdon, “Superoxide and Hydrogen Peroxide in Relation to Mammalian Cell Proliferation,” Free Radical Biology & Medicine, Vol. 18, 1995, pp. 775-794. doi:10.1016/0891-5849(94)00198-S

[18]   F. J. Blanco, R. L. Ochs, H. Schwarz and M. Lotz, “Chondrocyte Apoptosis ?nduced by Nitric Oxide,” American Journal of Pathology, Vol. 146, No. 1, 1995, pp. 75-85.

[19]   S. B. Abramson, M. Attur, A. R. Amin and R. Clancy, “Nitric Oxide and ?nflammatory Mediators in the Perpetuation of Osteoarthritis,” Current Rheumatology Reports, Vol. 3, No. 6, 2001, pp. 535-541.

[20]   D. Taskiran, M. Stefanovic-Racic, H. Georgescu and C. Evans, “Nitric Oxide Mediates Suppression of Cartilage Proteoglycan Synthesis by ?nterleukin-1,” Biochemical and Biophysical Research Communications, Vol. 200, No. 1, 1994, pp. 142-148.

[21]   Y. Hirai, K. Migita, S. Honda, Y. Ueki, S. Yamasaki and S. Urayama, et al., “Effects of Nitric Oxide on Matrix Metalloproteinase-2 Production by Rheumatoid Synovial Cells,” Life Sciences, Vol. 68, No. 8, 2001, pp. 913-920. doi:10.1016/S0024-3205(00)00998-X

[22]   R. M. Clancy, S. B. Abramson, C. Kohne and J. Rediske, “Nitric Oxide Attenuates Cellular Hexose Monophosphate Shunt Response to Oxidants in Articular Chondrocytes and Acts to Promote Oxidant ?njury,” Journal of Cellular Physiology, Vol. 172, No. 2, 1997, pp. 183-191.

[23]   N. Alaaeddine, J. A. Di Battista, J. P. Pelletier, J. M. Cloutier, K. Kiansa, et al., “Osteoarthritic Synovial Fibroblasts Possess an ?ncreased Level of Tumor Necrosis Factor-Receptor 55 (TNF-R55) That Mediates Biological Activation by TNF-Alpha,” Journal of Rheumtology, Vol. 24, No. 10, 1997, pp. 1985-1994.

[24]   M. Lotz, “The Role of Nitric Oxide in Articular Cartilage Damage,” Rheumatic Disease Clinics of North America, Vol. 25, No. 2, 1999, pp. 269-282.

[25]   A. Anandacoomarasamy and L. March, “Current Evidence for Osteoarthritis Treatments,” Therapeutic Advances in Musculoskeletal Disease, Vol. 2, No. 1, 2010, pp. 17-28.

[26]   M. Fajardo and P. E. Di Cesare, “Disease-Modifying Therapies for Osteoarthritis: Current Status,” Drugs Aging, Vol. 22, No. 2, 2005, pp. 141-161. doi:10.2165/00002512-200522020-00005

[27]   M. E. Zagaria, “Osteoarthritis in Seniors,” US Pharmacist, Vol. 31, No. 1, 2006, pp. 20-24.

[28]   S. K. Das, S. Ramakrishnan, K. Mishra, et al., “A Randomized Controlled Trial to Evaluate the Slow-Acting Symptom-Modifying Effects of Colchicine in Osteoarthritis of the Knee: A Preliminary Report,” Arthritis & Rheumatism, Vol. 47, No. 3, 2002, pp. 280-284. doi:10.1002/art.10455

[29]   M. Modriansky, Y. Y. Tyurina, V. A. Tyurin, T. Matsura, A. A. Shvedova, J. C. Yalowich and V. E. Kagan, “Anti-/ Pro-Oxidant Effects of Phenolic Compounds in Cells: Are Colchicine Metabolites Chain-Breaking Antioxidants?” Toxicology, Vol. 177, No. 1, 2002, pp. 105-117. doi:10.1016/S0300-483X(02)00199-3

[30]   D. Das, P. W. Pemberton, P. C. Burrows, C. Gordon, A. Smith, R. F. McMahon and T. W. Warnes, “Antioxidant Properties of Colchicine in Acute Carbon Tetrachloride ?nduced Rat Liver ?njury and ?ts Role in the Resolution of Established Cirrhosis,” Biochimica et Biophysica Acta, Vol. 1502, 2000, pp. 351-362. doi:10.1016/S0925-4439(00)00059-4

[31]   E. W. Chia, R. Grainger and J. L. Harper, “Colchicine Suppresses Neutrophil Superoxide Production in a Murine Model of Gouty Arthritis: A Rationale for Use of Low-Dose Colchicine,” British Journal of Pharmacology, Vol. 153, No. 6, 2008, pp. 1288-1295.

[32]   E. H. Tüzün, L. Eker, A. Aytar, A. Da?kapan and M. Bayramo?lu, “Acceptability, Reliability, Validity and Responsiveness of the Turkish Version of WOMAC Osteoarthritis Index,” Osteoarthritis Cartilage, Vol. 13, No. 1, 2005, pp. 28-33. doi:10.1016/j.joca.2004.10.010

[33]   K. R. Hegde, M. G. Henein and S. D. Varma, “Establishment of Mouse as an Animal Model for Study of Diabetic Cataracts: Biochemical Studies,” Diabetes, Obesity and Metabolism, Vol. 5, No. 2, 2003, pp. 113-119.

[34]   L. Ediz and I. Tekeo?lu, “Symptom Modifying Effect of Colchicine in Patients with Knee Osteoarthritis,” Journal of Clinical and Analytical Medicine, Vol. 3, No. 1, 2012, pp. 63-67. doi:10.4328/JCAM.563

[35]   A. Mahajan, S. Verma and V. Tandon, “Osteoarthritis,” Journal of the Association of Physicians of India, Vol. 53, 2005, pp. 634-641.

[36]   P. R. Colville-Nash and D. A. Willoughby, “COX-1, COX-2 and Articular Joint Disease: A Role of Chondro-protective Agents,” Biorheology, Vol. 39, No. 1-2, 2002, pp. 171-179.

 
 
Top