Advertisement

Oxyradicals, inflammation and drugs acting on oxyradical production

  • Dennis V. Parke
  • Andrew M. Symons
  • Ann L. Parke
Part of the Inflammation and Drug Therapy Series book series (IDTH, volume 3)

Abstract

Rheumatoid arthritis is a chronic systemic disease, with an autoimmune component, involving both humoral and cellular mechanisms. The biochemical mechanisms concerned are esoteric and involve the formation of immune complexes resulting in the production of oxygen radicals, with consequent damage of membranes, and activation of phospholipase A2. The subsequent release of arachidonate from membrane phospholipids leads to increased production of prostanoids. The production of oxygen radicals also results in the destruction of microsomal cytochromes, with impairment of corticosteroid biosynthesis, anaemia and accumulation of inorganic iron. All these molecular events, comprising a partly self-promoting cascade of chronic immunological injury, are considered to be initiated, at least originally, by an immune response to some infectious agent or ingested antigen and to be mediated by oxygen radicals (see Figure 1). However, although recent trends have been for physicians and pharmaceutical companies to exploit possible therapeutic benefits of oxygen radical scavengers and antioxidants in the treatment of rheumatoid disease, unequivocal evidence in vivo of oxygen radical involvement in arthritic tissue damage, and of therapeutic benefit of radical scavengers, is somewhat lacking1. This chapter is therefore directed to reviewing existing evidence for the participation of oxygen radicals in rheumatoid disease, and to consider the possible forms of treatment which involve inhibition of oxyradical production and prevention of oxyradical tissue damage.

Keywords

Rheumatoid Arthritis Rheumatoid Arthritis Patient Synovial Fluid Singlet Oxygen Oxygen Radical 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Greenwald, RA (1985). Therapeutic benefits of oxygen radical scavenger treatments remain unproven. J Rheumatol, 7, 212–214Google Scholar
  2. 2.
    Parekh, RB, Dwek, RA, Sutton, BJ et al. (1985). Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature (London), 316, 452–457CrossRefGoogle Scholar
  3. 3.
    Parke, DV and Symons, AM (1977). The biochemical pharmacology of mucus. In Elstein, D and Parke, DV (eds) Mucus in Health and Disease, pp. 423–441 (New York: Plenum)Google Scholar
  4. 4.
    Konttinen, YT, Nordstrom, D, Bergroth, V et al. (1986). Cell-mediated immune response in the diseased joints in patients with reactive arthritis. Scand J Immunol, 23, 685–691PubMedCrossRefGoogle Scholar
  5. 5.
    Bergroth, V, Konttinen, YT, Nykanen, P et al. (1985). Proliferating cells in the synovial fluid in rheumatic disease. Analysis with autoradiography-immunoperoxidase double staining. Scand J Immunol, 22, 383–391PubMedCrossRefGoogle Scholar
  6. 6.
    Cavender, D, Haskard D, Yu, C-L et al. (1987). Pathways to chronic inflammation in rheumatoid synovitis. Fed Proc, 46, 113–117PubMedGoogle Scholar
  7. 7.
    Henderson, B, Pettipher, ER and Higgs, GA (1987). Mediators of rheumatoid arthritis. Br Med Bull, 43, 415–428PubMedGoogle Scholar
  8. 8.
    Mochan, E, Uhl, J and Newton, R (1986). Interleukin I stimulation of synovial cell plasminogen activator production. J Rheumatol, 13, 15–19PubMedGoogle Scholar
  9. 9.
    Prince, RC and Gunson, DE (1987). Superoxide production by neutrophils. Trends Biochem Sci, 12, 86–87CrossRefGoogle Scholar
  10. 10.
    Vapaatalo, H (1986). Free radicals and anti-inflammatory drugs. Med Biol, 64, 1–7PubMedGoogle Scholar
  11. 11.
    Dowling, EJ, Jasani, MK, Parke, DV et al. (1985a). Free radicals lipid peroxidation and prostaglandins during the development and maintenance of foot-pad oedema in the Koch model. Br J Pharmacol, 84, 35PGoogle Scholar
  12. 12.
    Dowling, EJ, Jasani, MK, Parke, DV et al. (1985b). Characterisation of ex-vivo luminol-amplified chemiluminescence accompanying the initiation of foot-pad oedema in the Koch model. Br J Pharmacol, 84, 79PGoogle Scholar
  13. 13.
    Dowling, EJ, Symons, AM and Parke, DV (1986). Free radical production at the site of an acute inflammatory reaction as measured by chemiluminescence. Agents and Actions, 19, 203–207.PubMedCrossRefGoogle Scholar
  14. 14.
    Dowling, EJ, Symons, AM, Andrews, FJ and Blake, DR (1987). Reactive oxygen species, inflammation and drug evaluation. Br J Rheumatol, 26, Abstr Suppl, No.1, p. 19Google Scholar
  15. 15.
    Ozaki, Y, Ohashi, T and Niwa, Y (1986). Oxygen radical production by neutrophils from patients with bacterial infection and rheumatoid arthritis. Inflammation, 10, 119–130PubMedCrossRefGoogle Scholar
  16. 16.
    Biemond, P, Swaak, AJG, Penders, JMA et al. (1986). Superoxide production by polymorphonuclear leucocytes in rheumatoid arthritis and osteoarthritis: in vivo inhibition by the antirheumatic drug piroxicam due to interference with the activation of the NADPH-oxidase. Ann Rheum Dis, 45, 249–255PubMedCrossRefGoogle Scholar
  17. 17.
    Janoff, A (1975). At least three human neutrophil lysosomal proteases are capable of degrading joint connective tissues. Ann NY Acad Sci, 256, 402–408PubMedCrossRefGoogle Scholar
  18. 18.
    Niwa, Y, Sakane, T, Shingu, M and Yokoyama, M (1983). Effect of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes. A possible role of increased oxygen radicals generated by neutrophils. J Clin Immunol, 3, 228–240PubMedCrossRefGoogle Scholar
  19. 19.
    Bender, JG, van Epps, DE, Searles, R and Williams, RC Jr (1986). Altered function of synovial fluid granulocytes in patients with acute inflammatory arthritis: Evidence for activation of neutrophils and its mediation by a factor present in synovial fluid. Inflammation, 10, 443–453PubMedCrossRefGoogle Scholar
  20. 20.
    Niwa, Y, Sakane, T, Shingu, M and Miyachi, Y (1985). Role of stimulated neutrophils from patients with systemic lupus erythematosus in tissue injury, with special reference to serum factors and increased active oxygen species generated by neutrophils. Inflammation, 9, 163–172PubMedCrossRefGoogle Scholar
  21. 21.
    Kovacs, IB, Meyrick Thomas, RH, Mackay, AR et al. (1986). Increased chemilumi-nescence of polymorphonuclear leucocytes from patients with progressive systemic sclerosis. Clin Sci, 70, 257–261PubMedGoogle Scholar
  22. 22.
    Monboisse, JC, Braquet, P, Randoux, A and Borel, JP (1983). Non-enzymatic degradation of acid soluble calf skin collagen by superoxide ion: protective effects of flavonoids. Biochem Pharmacol, 32, 53–58PubMedCrossRefGoogle Scholar
  23. 23.
    Burkhardt, H, Schwingel, M, Menninger, H et al. (1986). Oxygen radicals as effectors of cartilage destruction: Direct degradative effect on matrix components and indirect action via activation of latent collagenase from polymorphonuclear leukocytes. Arthritis Rheum, 29, 379–387PubMedCrossRefGoogle Scholar
  24. 24.
    Blake, DR, Hall, ND, Treby, DA et al. (1981). Protection against superoxide and hydrogen peroxide in synovial fluid from rheumatoid patients. Clin Sci, 61, 483–486PubMedGoogle Scholar
  25. 25.
    van Kuijk, FJGM, Sevanian, A, Handelman, GJ and Dratz, EA (1987). A new major role for phospholipase A2: protection of membranes from lipid peroxidation damage. Trends Biochem Sci, 12, 31–34CrossRefGoogle Scholar
  26. 26.
    Trang, LE, Granstrom, E and Lovgren, O (1977). Levels of prostaglandins F2 and E2 and thromboxane B2 in joint fluid in rheumatoid arthritis. Scand J Rheumatol, 6, 151–154PubMedCrossRefGoogle Scholar
  27. 27.
    Salmon, JA, Higgs, GA, Vane, JR et al. (1983). Synthesis of arachidonate cyclooxygenase products by rheumatoid and non-rheumatoid synovial lining in non-proliferative organ culture. Ann Rheum Dis, 42, 36–39PubMedCrossRefGoogle Scholar
  28. 28.
    Moilanen, E, Seppala, E, Nissila, M and Vapaatalo, H (1987). Differences in prostanoid production between healthy and rheumatic synovia in vitro. Agents Actions, 20, 98–103PubMedCrossRefGoogle Scholar
  29. 29.
    Seitz, M, Deimann, W, Gram, N et al. (1982). Characterisation of blood mononuclear cells of rheumatoid arthritis patients. I. Depressed lymphocyte proliferation and enhanced prostanoid release from monocytes. Clin Immunol Immunopathol, 25, 405–416PubMedCrossRefGoogle Scholar
  30. 30.
    Bomalaski, JS, Clark, MA and Zurier, RB (1986). Enhanced phospholipase activity in peripheral blood monocytes from patients with rheumatoid arthritis. Arthritis Rlieum, 29, 312–318CrossRefGoogle Scholar
  31. 31.
    Flower, RJ (1985). Background and discovery of lipocortins. Agents Actions, 17, 255–262CrossRefGoogle Scholar
  32. 32.
    Hirata, F, del Carmine, R, Nelson, CA et al. (1981). Presence of autoantibody for phospholipase inhibitory protein, lipomodulin, in patients with rheumatic diseases. Proc Natl Acad Sci, USA, 78, 3190–3194PubMedCrossRefGoogle Scholar
  33. 33.
    Buchar, E and Janku, I (1985). The effect of adjuvant-induced arthritis on rat liver microsomal phospholipid metabolism. Methods Findings Exp Clin Pharmacol, 7, 469–472Google Scholar
  34. 34.
    Salmon, JA and Higgs, GA (1987). Prostaglandins and leukotrienes as inflammatory mediators. Br Med Bull, 43, 285–296PubMedGoogle Scholar
  35. 35.
    Reilly, IAG, Roy, L and Fitzgerald, GA (1986). Biosynthesis of thromboxane in patients with systemic sclerosis and Raynaud’s phenomenon. Br Med J, 292, 1037–1039CrossRefGoogle Scholar
  36. 36.
    Editorial (1985). Metal chelation therapy, oxygen radicals and human disease. Lancet, i, 143–145Google Scholar
  37. 37.
    Biemond, P, Swaak, AJG, van Eijk, HG and Koster, JF (1986). Intraarticular ferritin-bound iron in rheumatoid arthritis. Arthritis Rheum, 29, 1187–1193PubMedCrossRefGoogle Scholar
  38. 38.
    Blake, DR, Hall, ND, Bacon, PA et al. (1981). The importance of iron in rheumatoid disease. Lancet, ii, 1142–1144CrossRefGoogle Scholar
  39. 39.
    Rowley, D, Gutteridge, JMC, Blake, D et al. (1984). Lipid peroxidation in rheumatoid arthritis: thiobarbituric-acid reactive material and catalytic iron salts in synovial fluid from rheumatoid patients. Clin Sci, 66, 691–695PubMedGoogle Scholar
  40. 40.
    Winyard, PG, Blake, DR, Chirico, S et al. (1987). Mechanism of exacerbation of rheumatoid synovitis by total-dose iron-dextran infusion: in vivo demonstration of iron-promoted oxidant stress. Lancet, i, 69–72CrossRefGoogle Scholar
  41. 41.
    Vane, JR (1971). Inhibition of prostaglandin synthesis as a mechanism of action for aspirin like drugs. Nature New Biol, 231, 232–235PubMedGoogle Scholar
  42. 42.
    Gay, JC, Lukens, JN and English, DK (1984). Differential inhibition of neutrophil superoxide generation by non-steroidal anti-inflammatory drugs. Inflammation, 8, 209–222PubMedCrossRefGoogle Scholar
  43. 43.
    Harth, M, Keown, PA and Orange, JF (1983). Monocyte dependent excited oxygen radical generation in rheumatoid arthritis: inhibition by gold sodium thiomalate. J Rheumatol, 10, 701–707PubMedGoogle Scholar
  44. 44.
    Pinals, RS, Kaplan, SB, Lawson, JG and Hepburn, B (1986). Sulfasalazine in rheumatoid arthritis. A double-blind, placebo-controlled trial. Arthritis Rheum, 29, 1427–1434PubMedCrossRefGoogle Scholar
  45. 45.
    Miyachi, Y, Yoshioka, A, Imamura, S and Niwa, Y (1987). Effect of sulphasalazine and its metabolites on the generation of reactive oxygen species. Gut, 28, 190–195PubMedCrossRefGoogle Scholar
  46. 46.
    Prouse, P, Shawe, D and Gumpel, JM (1987). Macrocytic anaemia in patients treated with sulphasalazine for rheumatoid arthritis. Br Med J, 294, 904–905CrossRefGoogle Scholar
  47. 47.
    Muller-Peddinghaus, R and Wurl, M (1987). The amplified chemiluminescence test to characterize antirheumatic drugs as oxygen radical scavengers. Biochem Pharmacol, 36, 1125–1132PubMedCrossRefGoogle Scholar
  48. 48.
    Cuperus, RA, Muijsers, AO and Wever, R (1985). Antiarthritic drugs containing thiol groups scavenge hypochlorite and inhibit its formation by myeloperoxidase from human leukocytes. Arthritis Rheum, 28, 1128–1133CrossRefGoogle Scholar
  49. 49.
    Madhok, R, Capell, HA and Waring, R (1987). Does sulphoxidation state predict gold toxicity in rheumatoid arthritis. Br Med J, 294, 483CrossRefGoogle Scholar
  50. 49a.
    Pekoe, G, Van Dyke, K, Peden, D et al. (1982). Antioxidant theory of non-steroidal anti-inflammatory drugs based on the inhibition of luminol-enhanced chemiluminescence from the myeloperoxidase reaction. Agents Actions, 12, 371–376PubMedCrossRefGoogle Scholar
  51. 50.
    Staite, ND, Messner, RP and Zoschke, DC (1985). In vitro production and scavenging of hydrogen peroxide by D-penicillamine. Arthritis Rheum, 28, 914–921PubMedCrossRefGoogle Scholar
  52. 51.
    Corey, EJ, Mehrotra, MM and Khan, AU (1987). Antiarthritic gold compounds effectively quench electronically excited singlet oxygen. Science, 236, 68–69PubMedCrossRefGoogle Scholar
  53. 52.
    Cleland, LG, Betts, WH, Vernon-Roberts, B and Bielicki, J (1982). Role of iron and influence of anti-inflammatory drugs on oxygen-derived free radical production and reactivity. J Rheumatol, 9, 885–892PubMedGoogle Scholar
  54. 53.
    Shimada, O and Yasuda, H (1986). Hydroxyl radical scavenging action of tinoridine. Agents Actions, 19, 208–214PubMedCrossRefGoogle Scholar
  55. 54.
    Sugioka, K, Shimosegawa, Y and Nakano, M (1987). Estrogens as natural antioxidants of membrane phospholipid peroxidation. FEBS Lett, 210, 37–39PubMedCrossRefGoogle Scholar
  56. 55.
    Parke, AL (1985). Rheumatoid arthritis and oral contraceptives. Intern Med, 6, 105–111CrossRefGoogle Scholar
  57. 56.
    Halliwell, B, Gutteridge, JMC and Blake, D (1985). Metal ions and oxygen radical reactions in human inflammatory joint disease. Phil Trans R Soc, Lond, B, 311, 659–671CrossRefGoogle Scholar
  58. 57.
    Giordano, N, Sancasciani, S, Borghi, C et al. (1986). Antianaemic and potential antiinflammatory activity of desferoxamine: possible usefulness in rheumatoid arthritis. Clin Exp Rheumatol, 4, 25–29PubMedGoogle Scholar
  59. 58.
    Poison, RJ, Jawad, ASM, Bomford, A et al. (1986). Treatment of rheumatoid arthritis and desferoxamine. Q J Med, N.S., 61, 1153–1158Google Scholar
  60. 59.
    Orton, RB, de Veber, LL and Sulh, HMB (1985). Ocular and auditory toxicity of long-term, high-dose, subcutaneous desferoxamine therapy. Can J Ophthalmol, 20, 153–156PubMedGoogle Scholar
  61. 60.
    Poison, RJ, Jawad, A, Bomford, A et al. (1985). Treatment of rheumatoid arthritis with desferoxamine: relation between stores of iron before treatment and side effects. Br Med J, 291,(ii), 448Google Scholar
  62. 61.
    Longeville, A and Crichton, RR (1986). An animal model of iron overload and its application to study hepatic ferritin iron mobilisation by chelators. Biochem Pharmacol, 35, 3669–3678CrossRefGoogle Scholar
  63. 62.
    Haataja, M, Nissila, M and Ruutsalo, H-M (1978). Serum sulphydryl levels in rheumatoid patients treated with gold thiomalate and penicillamine. Scand J Rheumatol, 7, 212–214PubMedCrossRefGoogle Scholar
  64. 63.
    Munthe, E, Kass, E and Jellum, E (1981). D-Penicillamine-induced increase in intracellular glutathione correlating to clinical response in rheumatoid arthritis. J Rheumatol, 8,Suppl. 7, 14–19Google Scholar
  65. 64.
    Sree Kumar, K, Chirigos, MA and Weiss, JF (1979). Protection of rat liver microsomes from NADPH-, ascorbate-, and X-irradiation-induced lipid peroxidation by levamisole. Int J Immunopharmacol, 1, 85–91CrossRefGoogle Scholar
  66. 65.
    Tarp, U, Overvad, K, Thorling, EB et al. (1985). Selenium treatment in rheumatoid arthritis. Scand J Rheumatol, 14, 364–368PubMedCrossRefGoogle Scholar
  67. 66.
    McCord, JM, Stokes, SH and Wong, K (1979). Superoxide radicals as phagocyte-produced chemical mediators of inflammation. In Weissmann, G (ed) Advances in Inflammation Research. (New York: Raven Press), Vol. 1, pp. 273–280Google Scholar
  68. 67.
    Boctor, AM and Pugsley, TA (1986). Effect of CI-922, a potential new antiallergy agent, on arachidonic acid metabolism in vitro. Inflammation, 10, 435–441PubMedCrossRefGoogle Scholar
  69. 68.
    Hope, WC, Welton, AF, Fielder-Nagy, C et al. (1983). In vitro inhibition of the biosynthesis of slow-reacting substance of anaphylaxis (SRS-A) and lipoxygenase activity by quercetin. Biochem Pharmacol, 32, 367–371PubMedCrossRefGoogle Scholar
  70. 69.
    Capasso, F, Tavares, IA, Tsang, R and Bennett, A (1985). Effects of d-penicillamine, levamisole and tiopronin on eicosanoid synthesis by rat gut tissue. Agents Actions, 17, 395–396CrossRefGoogle Scholar
  71. 70.
    Lee, TH, Hoover, RL, Williams, JD et al. (1985). Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med, 312, 1217–1224PubMedCrossRefGoogle Scholar
  72. 71.
    Leslie, CA, Gonnerman, WA, Ullman, MD et al. (1985). Dietary fish oil modules macrophage fatty acids and decreases arthritis susceptibility in mice. J Exp Med, 162, 1336–1349PubMedCrossRefGoogle Scholar
  73. 72.
    Prickett, JD, Trentham, DE and Robinson, DR (1984). Dietary fish oil augments the induction of arthritis in rats immunized with type II collagen. J Immunol, 132, 725–729PubMedGoogle Scholar
  74. 73.
    Kremer, JM, Bigaouette, J, Michalek, AV et al. (1985). Effects of manipulation of dietary fatty acids on clinical manifestations of rheumatoid arthritis. Lancet, 1, 184–187PubMedCrossRefGoogle Scholar
  75. 74.
    Kremer, JM, Jubiz, W, Michalek, A et al. (1987). Fish-oil fatty acid supplementation in active rheumatoid arthritis. Ann Intern Med, 106, 497–502PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Dennis V. Parke
    • 1
    • 2
  • Andrew M. Symons
    • 1
    • 2
  • Ann L. Parke
    • 1
    • 2
  1. 1.Department of BiochemistryUniversity of SurreyGuildfordUK
  2. 2.Division of Rheumatic DiseasesUniversity of Connecticut Health CenterFarmingtonUSA

Personalised recommendations