Abstract
Arthritis is a joint disorder where the joint damage is associated with elevated levels of inflammatory mediators and reactive oxygen species (ROS). The inflammatory hyperalgesia associated with arthritis has been shown to be attenuated by anti-hyperlipidemic drug, atorvastatin. The present study was carried out to evaluate the effect of atorvastatin on joint inflammation and associated oxidative stress markers in a rat model where arthritis was induced by inra-articular injection of 0.1 ml of 0.1% Freund’s Complete Adjuvant (FCA). Atorvastatin (10 mg and 50 mg/kg) and diclofenac (5 mg/kg) were administered orally, daily during the study period of 4 days and their effect on joint inflammation was evaluated by measuring joint diameter, levels of glutathione (GSH), thiobarbituric acid reactive substances (TBARS), activity of super oxide dismutase (SOD) and tissue histology. Atorvastatin produced a dose-dependent reduction in joint inflammation that was associated with normalization of levels of oxidative stress markers and tissue histology and its effect was found to be comparable to that of diclofenac.
Similar content being viewed by others
References
Abramson SB, Attur M, Amin AR, Clancy R (2001) Nitric oxide and inflammatory mediators in the perpetuation of osteoarthritis. Curr Rheumatol Rep 3:535–541
Adam O, Laufs U (2008) Antioxidative effects of statins. Arch Toxicol 82:885–892
Barsante MM, Roffé E, Yokoro CM, Tafuri WL, Souza DG, Pinho V et al (2005) Anti-inflammatory and analgesic effects of atorvastatin in a rat model of adjuvant induced arthritis. Eur J Pharmacol 516:282–289
Blum A, Shamburek R (2009) The pleiotropic effects of statins on endothelial function, vascular inflammation, immunomodulation and thrombogenesis. Atherosclerosis 203:325–330
Bradford MM (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Butler SH, Godefroy F, Besson JM, Weil-Fugazza J (1992) A limited arthritic model for chronic pain studies in the rat. Pain 48:73–81
Cerhan JR, Saag KG, Merlino LA, Mikuls TR, Criswell LA (2003) Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort older women. Am J Epidemiol 157:345–354
Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA et al (1998) Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 279:1615–1622
Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77
Funk JL, Chen J, Downey KJ, Clark RA (2008) Bone protective effect of simvastatin in experimental arthritis. J Rheumatol 35:1083–1091
Ghaisas MM, Dandawate PR, Zawar SA, Ahire YS, Gandhi SP (2010). Antioxidant, antinoceptive and anti-inflammatory activities of atorvastatin and rosuvastatin in various experimental models. Inflammopharmacology 18:169–177
Haflah NH, Jaarin K, Abdullah S, Omar M (2009) Palm vitamin E and glucosamine sulphate in the treatment of osteoarthritis of the knee. Saudi Med J 30:1432–1438
Hershko AY, Rivera J (2010) Mast cell and T cell communication; amplification and control of adaptive immunity. Immunol Lett 128:98–104
Hitchon CA, EL-Gabalawy HS (2004) Oxidation in rheumatoid arthritis. Arthritis Res Ther 6:265–278
Kakkar P, Das B, Vishwanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21:130–132
Kohen R, Nyska A (2002) Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions and methods for their quantification. Toxicol Pathol 30:620–650
Lansberg P (2009) Pleiotropic effects of statins and beyond. Cardiology 112:1–3
Leung BP, Sattar N, Crilly A, Prach M, McCarey DW, Payne H et al (2003) A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol 170:1524–1530
Majlesi Y, Samorapoompichit P, Hauswirth AW, Schernthaner GH, Ghannadan M Baghestanian M et al (2003) Cerivastatin and atorvastatin inhibit IL-3-dependent differentiation and IgE-mediated histamine release in human basophils and downmodulate expression of the basophil-activation antigen CD203c/E-NPP3. J Leukoc Biol 73:107–117
McCarey DW, Mclnnes IB, Madhok R, Hampson R, Scherbakov O, Ford I et al (2004) Trial of atorvastatin in rheumatoid arthritis (TARA): double-blind, randomized placebo-controlled trial. Lancet 363:2015–2021
Nasu K, Tsuchikane E, Katoh O, Tanaka N, Kimura M, Ehara M et al (2009) Effect of fluvastatin on progression of coronary atherosclerotic plaque evaluated by virtual histology intravascular ultrasound. JACC Cardiovasc Interv 2:689–696
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Remans PH, van Oosterhout M, Smeets TJ, Sanders M, Frederiks WM, Reedquist KA et al (2005) Intracellular free radical production in synovial T lymphocytes from patients with rheumatoid arthritis. Arthritis Rheum 52:2003–2009
Sawara Y, Takei T, Uchida K, Ogawa T, Yoshida T, Tsuchiya K et al (2008) Effects of lipid-lowering therapy with rosuvastatin on atherosclerotic burden in patients with chronic kidney disease. Intern Med 47:1505–1510
Shaw SM, Fildes JE, Yonan N, Williams SG (2009) Pleiotropic effects and cholesterol-lowering therapy. Cardiology 112:4–12
Szekanecz Z, Halloran MM, Volin MV, Woods JM, Strieter RM, Kenneth Haines G 3rd et al (2000) Temporal expression of inflammatory cytokines and chemokines in rat adjuvant-induced arthritis. Arthritis Rheum 43:1266–1277
Van Doornum S, McColl G, Wicks IP (2004) Atorvastatin reduces arterial stiffness in patients with rheumatoid arthritis. Ann Rheum Dis 63:1571–1575
Wahane VD, Kumar VL (2010) Atorvastatin ameliorates inflammatory hyperalgesia in rat model of monoarticular arthritis. Pharmacol Res 61:329–333
Yamada K, Nakamura T, Utsumi H (2006) Enhanced intraarticular free radical reactions in adjuvant arthritis rats. Free Radic Res 40:455–460
Yamagata T, Kinoshita K, Nozaki Y, Sugiyama M, Ikoma S, Funauchi M (2007) Effects of pravastatin in murine collagen-induced arthritis. Rheumatol Int 27:531–539
Yokota K, Miyazaki T, Hirano M, Alciyama Y, Mimura T (2006) Simvastatin inhibits production of interleukin 6 (IL-6) and IL-8 and cell proliferation induced by tumor necrosis factor-alpha in fibroblast-like synoviocytes from patients with rheumatoid arthritis. J Rheumatol 33:463–471
Yudoh K, Nguyen T, Nakamura H, Hongo-Masuko K, Kato T, Nishioka K (2003) Potential involvement of oxidative stress in cartilage senescence and development of osteoarthritis: oxidative stress induces chondrocyte telomere instability and downregulation of chondrocyte function. Arthritis Res Ther 7:380–391
Zarbock A, Ley K (2009) Neutrophil adhesion and activation under flow. Microcirculation 16:31–42
Author information
Authors and Affiliations
Corresponding author
Additional information
An erratum to this article can be found online at http://dx.doi.org/10.1007/s10787-013-0185-5.
Rights and permissions
About this article
Cite this article
Kumar, V.L., Guruprasad, B. & Wahane, V.D. Atorvastatin exhibits anti-inflammatory and anti-oxidant properties in adjuvant-induced monoarthritis. Inflammopharmacol 18, 303–308 (2010). https://doi.org/10.1007/s10787-010-0057-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-010-0057-1