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OXIDATIVE STRESS IN SYSTEMIC SCLEROSIS

Year 2010, Volume: 4 Issue: 2, 90 - 96, 25.07.2010

Şükran Erten

Abstract

SSc is a chronic disease of connective tissue causing inflammation, fibrosis and degenerative changes of blood vessels, skin, synovium, skeletal muscle and internal organs like gastrointestinal system , lungs, heart and the kidneys. Etiopathogenesis of the systemic sclerosis is not well known and oxidative stres has been thought to play a role on endothelial damage at early stages of the disease. It was also shown by in vivo and in vitro studies in last ten years that exess free radical production plays a role in pathophysiology of SSc. Functional dysfunction of endothelial cells is mostly seen at early stages of the disease. Ischemia can cause tissue damage especially when it is together with hypoxia. Activated oxygen derivatives both initiate and promote ishemic tissue damage. These include hypoxanthine-xanthin oxidase system, impaired mitochondrial electron transport sytem, activated PMNLs and arachidonic acid mechanism by lipoxygenase pathway. Raynaud phenomenon is associated with proliferative vascular occlusive disease and ultimately increase in oxygen free radicals and tissue damage. Activation of inflammatory cells and oxidative damage biomarkers is much more pronounced at early stages of the disease where there is more intact tissue. Vascular damage may accelerate oxidative stress by stimulating methabolic pathways.

Keywords

Systemic sclerosis oxidative stress antioxidants

References

  • 1. LeRoy EC, Medsger TA Jr. Criteria for the classification of early systemic sclerosis. J. Rheumatol 2001 ;28: 1573-76
  • 2. Matucci Cerinic M, Kahaleh BM, LeRoy EC. The vascular involvement in systemic sclerosis. In: Clements PJ, Furst DE, eds. Systemic Sclerosis. 2nd ed. Williams and Wilkins; Baltimore, 1996.p.153-74
  • 3. Herrick AL, Matucci Cerinic M. The emerging problem of oxidative stress and the role of antioxidants in systemic sclerosis. Clin Exp Rheumatol 2001;19:4-8
  • 4. Marasini M, Cugno M, Bassani C, Stan-zoni M, Bottasso B, Agostoni A. Tissuetype plasminogen activator and Von Willebrand Factor plasma levels as marker of endothelial involvement in patients with Raynaud’s phenomenon. Int Microcirc Clin Exp1992;11:375-82
  • 5. Murrel DF. A radical proposal for the pathogenesis of scleroderma. J. Am Acad Dermatol 1993;28:78-85
  • 6. McCord JM. Oxygen-derived free radicals in postischemic tissue injury. Lancet 1985;312:159-63
  • 7. Blake DR, Merry P, Unsworth J. Hypoxic-reperfusion injury in the inflamed knee joint. Lancet 1989;1:289-93
  • 8. Halliwel B. Free radicals, antioxidants, and human disease. Curiosity, cause, or consequence? Lancet 1989;1:289-93
  • 9. Gabrielli A, Svegliati S, Moroncini G, Pomponio G, Santillo M, Awedimento EV. Oxidative stress and the pathogenesis of scleroderma: the Murrell’s hypothesis revisited. Semin. Immunopathol. 2008;30: 329-337
  • 10. Devrim E, Erten S, Erguder IB, Namuslu M, Turgay M, Durak I. Malondialdehyde and nitric oxide levels in erythrocytes from patients with systemic sclerosis. Med Prine Pract. 2008;17(4):349-50
  • 11. Sambo P, Jannino L, Candela M. Monocytes of patients with systemic sclerosis (scleroderma) spontaneously release in vitro increased amounts of superoxide anion. J Invest Dermatol 1999;112:78-84
  • 12. Morita A, Minami H, Sakakiba N, Sato K, Tsuji T. Elevated plasma superoxide dismutase activity in patients with systemic sclerosis. J Dermatol Sci 1996;11:196-201
  • 13. Cotton SA, Emerit I. Endothelial expression of nitric oxide synthases and nitrotyrosine in systemic sclerosis skin. J Pathol 1999; 189:273-8
  • 14. Emerit I, Filipe P, Meunier P, Auclair C, Freitas J, DeroussentA, GouyetteA, Fernandes A. Clastogenic activity in plasma of scleroderma patients: a biomarker of oxidative stress. Dermatology 1997;194:140-6
  • 15. Solans R, Motta C, Sola R. Abnormalities of erythrocyte membrane fluidity, lipid composition, and lipid peroxidation in systemic sclerosis:evidence of free radical mediated-injury. Arthritis Rheum 2000;43:894-900
  • 16. Stein CM, Tanner SB, Award JA. Evidence of free radical mediated injury (isoprostane overproduction) in scleroderma. Arthritis Rheum 1996;39:1146-50
  • 17 Cracowski JL, Marpeau C, Carpentier PH. Enhanced in vivo lipid peroxidation in scleroderma spectrum disorders. Arthritis Rheum 2001;44:1143-8
  • 18. Cracowski JL, Carpentier Ph, Imbert B. Increased urinary F2-isoprostanes in systemic sclerosis, but not in primary Raynaud’s Phenomenon. Arhritis Rheum 2002;46:1319-23
  • 19. Rottoli P, Magi B, Cianti R, Bargagli E, Va-gaggini C, Nikiforakis N, et al. Carbonylated proteins in bronchoalveolar lavage of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis. Proteomics 2005;5:2612-18
  • 20. İyidir ÖT, Erten S. Bağ dokusu hastalıklarında otoantikorların klinikte kullanımı. Clinical evaluation of autoantibodies in connective tissue disorders. Türkiye Klinikleri J Med Sci 2007, 27:236-246
  • 21. Lau AT, He QY, Chiu JF. A proteome analysis of the arsenite response in cultured lung cells: evidence for in vitro oxidative stress-induced apoptosis. Biochem. J. 2004; 382:641-50
  • 22. Montuschi P, Ciabattoni G, Paredi P. 8-iso-prostane as a biomarker of oxidative stress in interstitial lung diseases. Am J Resp Crit Care Med 1998;158:1524-7
  • 23. Caramaschi P, Martinelli N, Biasi D, Carletto A, Faccini G, Volpe A, et al. Homocysteine plasma concentration is related to lung impairment in scleroderma. Journal of Rheu- matology 2003;30:298-304
  • 24. Cope KA, Solga SF, Hummers LK, Wigley FM, Diehl AM, Risby TH. Abnormal exhaled ethane concentrations in scleroderma. Biomarkers 2006; 11(1):70-84
  • 25. Simonini G, Cerinic MM, Generini S, Zoppi M, Anichini M, Cesaretti C, Pignone A, Fal-cini F, Lotti T, Cagnoni M. Oxidative stress in systemic sclerosis. Mol Cell Biochem 1999;196:85-91
  • 26. Granger DN, Rutili G, Mccord JM. Superoxide radicals in feline intestinal ischemia. Gastroenterology 1981 ;81:22-9
  • 27. Bulkley GB. Reactive oxygen metabolites and reperfusion injury: Aberrant triggerin of reticuloendothelial function. Lancet 1994;344:934-6
  • 28 Denton CP, Bickerstaff MCM, Shiwen X. Serial circulating adhesion molecule levels reflect disease severity in systemic sclerosis. Br J Rheumatol 1995;34:1048-54
  • 29. Bland AD, Herrick A, Jayson MIV. Altered levels of soluble adhesion molecules in rheumatoid arhritis, vasculitis and systemic sclerosis. Br J Rheumatol 1995;34:814-9
  • 30. Anderson GN, Caidahl K, Kazzam E. Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis. Arhritis Rheum 2000;43:1085-93
  • 31. Mcinnes IB, Leung BP, Field M, Wei XO. Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients. J Exp Med 1996;184:1519-24
  • 32. Yamamoto T, Sawada Y, Katayama I, Nishioka K. Increased production of nitric oxide stimulated by interleukin-1 b in peripheral blood mononuclear cells in patients with systemic sclerosis. Br J Rheum 1998;37:1123-5
  • 33. Cavallo G, Sabadini L, Rollo L. Nitric oxide synthesis in peripheral blood mononuclear and polymorphonuclear cells from patients with systemic sclerosis. Rheumatology 1999;38:1301-4
  • 34. Matucci Cerinic M, Generini S, Pignone A, Cagnoni M. From Raynaud’s phenomenon to systemic sclerosis (scleroderma). Lack or exhaustion of adaptation? Ad Organ Biol 1998;6:241-53
  • 35. Housset E, Emerit I, Baulon A, De Grouchy J. Anomalies chromosomiques dans la scle-rodermie generalisee. Etude de dix malades. CR Acad Sci (Paris) 1969;269:413-19
  • 36. Peng SL, Fatenejad S, Craft J. Scleroderma:A disease related to damaged proteins? Nature Med 1997;3:276-8
  • 37. Halliwell B, Chirico S. Lipid peroxidation: Its mechanism, measurement, and significance. Am J Clin Nut 1993;57(suppl.):715-25
  • 38. Witztum JL, Steinberg D. Role of oxidised low density lipoprotein in atherogenesis. J Clin Invest 1991;88:1785-92
  • 39. Herrick AL, Illingworth KJ; Hollis S, Gomez-Zumaquero JM, Tinahones FJ: Antibodies against oxidised low density lipoproteins in systemic sclerosis. Rheumatology (Oxford) 2001;40(4):401-5
  • 40. Ingrassia TS, Ryu JH, Trastek VF, Rosenow EC. Oxygen exacerbated bleomycin pulmonary toxicity. Mayo Clin Oroc 1991;66:173-8
  • 41. Yoshida SH, German JB, Fletcher MP, Gershwin ME. The toxic oil syndrome: A perspective on immunotoxicologic mechanisms. Regul Toxicol Pharmacol 1994 Feb;19(1):60-79
  • 42. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 2nd ed. Oxford:Clarendon press; 1989. p.89
  • 43. Halliwell B, Gutteridge JMC, Cross CE. Free radicals, antioxidants and human disease: where are now? J Lab Clin Med 1992;119:589-620
  • 44. Wayner DDM, Burton GW, Ingold KU, Barclay LRC, Locke SJ. The relative contributions of vitamin E, urate, ascorbate and proteins to the peroxylradical trapping capacity of human blood plasma. Biochem Biophys Acta 1987;924:408-19
  • 45. Burton GW, Traber MG. Vitamin E: antioxidant activity, biokinetics and bioavailability. Ann Rev Nutr 1990;10:281-5
  • 46. Halliwell B, Grootveld M. The measurement of free radical reactions in humans. Some thoughts for future experimentation. FEBS Lett 1987;213:9-14
  • 47. Cranfield LM, Gollan JL, White AG, Doman-dy TL. Serum antioxidant activity in normal and abnormal subjects. Ann Clin Biochem 1979 Nov;16(6):299-306
  • 48. Me Quaid KE, Keenan AK. Endothelial barrier dysfunction and oxidative stress: roles for nitric oxide? Exp Physiol 1997;82:369-76
  • 49. Kaneko M, Hayashi J, Sato I, Miyasaka N. Probukol downregulates E-selectin expression on cultured human vascular endpthe-lial cells. Arterioscler Thromb Vase Biol 1996;16:1047-51
  • 50. Keaney JF, Xu A, Cunningham D, Jackson T, Frei B, Vita JA. Dietary probucol deserves endothelial functions in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation. J Clin Invest 1995;95:2520-9
  • 51. Reither RJ. Oxidative damage in the central nervous system: protection by melatonin. Prog Neurobiol 1998;56:359-84
  • 52. Reiter RJ, Tan DX, Cabrera J, et al. The oxi-dant/antioxidant network: role of melatonin. Biol Signals Recept 1999;8:56-63
  • 53. Wayne MC, Hazel SJ, Coull BM. Lazaroids. Drugs 1995;50:863-971
  • 54. Del Maestro RF, Thaw HH, Bjork J. Free radicals as mediators of tissue injury. Acta Physiol Scand 1980,492:43-57

SİSTEMİK SKLEROZDA OKSİDATİF STRES

Year 2010, Volume: 4 Issue: 2, 90 - 96, 25.07.2010

Şükran Erten

Abstract

Sistemik skleroz (SSc), bağ dokusunun kan damarlarında, deride, sinoviumda, iskelet kasında ve gastrointestinal sistem, akciğerler, kalp ve böbrekler gibi bazı iç organlarda infla-masyon, fibrozis ve dejeneratif değişikliklere yol açan kronik bir hastalığıdır. Sistemik sklerozun etyopatogenezi iyi bilinmemektedir ve başlangıç dönemindeki endotel hasarında oksidatif stresin rol oynadığı düşünülmektedir. Son 10 yıl içinde in vitro ve in vivo yapılan çalışmalarda da, aşırı serbest radikal üretiminin, sistemik skleroz patofizyolojisinde rol oynadığı gösterilmiştir. Endotel hücrelerinin fonksiyonel bozukluğu en çok hastalığın erken dönemlerinde ortaya çıkar. İskeminin kendisi özellikle de hipoksiyle birlikteyse doku hasarına neden olabilir. Aktive olmuş oksijen türevleri, hasarı hem başlatıp her de ilerlemesine neden olurlar. Bunlar arasında hipoksantin-ksantin oksidaz sistemi, bozulmuş mitokondrial elektron transport sistemi, aktive olmuş polimorfonük-leer lökositler(PMNL)’ler ve lipoksijenaz yoluyla araşidonik asit metabolizması vardır. Sistemik sklerozda Raynaud Fenomeni, proliferatif okluzif vasküler hastalıkla ve sonuçta serbest oksijen radikallerinde artışla ve doku hasarıyla ilişkilidir. İnflamatuvar hücrelerin ve oksidatif hasar biyo-markırlarının aktivasyonu, iskemik atakların daha sık olduğu ve daha fazla sağlam dokunun bulunduğu, hastalığın erken döneminde daha fazladır. Vasküler hastalık, metabolik yolları uyararak oksidatif stresi artırabilir.

Dr. Şükran ERTEN,
Dr. Murat TURGAY

Keywords

Sistemik skleroz oksidatif stress antioksidan.

References

  • 1. LeRoy EC, Medsger TA Jr. Criteria for the classification of early systemic sclerosis. J. Rheumatol 2001 ;28: 1573-76
  • 2. Matucci Cerinic M, Kahaleh BM, LeRoy EC. The vascular involvement in systemic sclerosis. In: Clements PJ, Furst DE, eds. Systemic Sclerosis. 2nd ed. Williams and Wilkins; Baltimore, 1996.p.153-74
  • 3. Herrick AL, Matucci Cerinic M. The emerging problem of oxidative stress and the role of antioxidants in systemic sclerosis. Clin Exp Rheumatol 2001;19:4-8
  • 4. Marasini M, Cugno M, Bassani C, Stan-zoni M, Bottasso B, Agostoni A. Tissuetype plasminogen activator and Von Willebrand Factor plasma levels as marker of endothelial involvement in patients with Raynaud’s phenomenon. Int Microcirc Clin Exp1992;11:375-82
  • 5. Murrel DF. A radical proposal for the pathogenesis of scleroderma. J. Am Acad Dermatol 1993;28:78-85
  • 6. McCord JM. Oxygen-derived free radicals in postischemic tissue injury. Lancet 1985;312:159-63
  • 7. Blake DR, Merry P, Unsworth J. Hypoxic-reperfusion injury in the inflamed knee joint. Lancet 1989;1:289-93
  • 8. Halliwel B. Free radicals, antioxidants, and human disease. Curiosity, cause, or consequence? Lancet 1989;1:289-93
  • 9. Gabrielli A, Svegliati S, Moroncini G, Pomponio G, Santillo M, Awedimento EV. Oxidative stress and the pathogenesis of scleroderma: the Murrell’s hypothesis revisited. Semin. Immunopathol. 2008;30: 329-337
  • 10. Devrim E, Erten S, Erguder IB, Namuslu M, Turgay M, Durak I. Malondialdehyde and nitric oxide levels in erythrocytes from patients with systemic sclerosis. Med Prine Pract. 2008;17(4):349-50
  • 11. Sambo P, Jannino L, Candela M. Monocytes of patients with systemic sclerosis (scleroderma) spontaneously release in vitro increased amounts of superoxide anion. J Invest Dermatol 1999;112:78-84
  • 12. Morita A, Minami H, Sakakiba N, Sato K, Tsuji T. Elevated plasma superoxide dismutase activity in patients with systemic sclerosis. J Dermatol Sci 1996;11:196-201
  • 13. Cotton SA, Emerit I. Endothelial expression of nitric oxide synthases and nitrotyrosine in systemic sclerosis skin. J Pathol 1999; 189:273-8
  • 14. Emerit I, Filipe P, Meunier P, Auclair C, Freitas J, DeroussentA, GouyetteA, Fernandes A. Clastogenic activity in plasma of scleroderma patients: a biomarker of oxidative stress. Dermatology 1997;194:140-6
  • 15. Solans R, Motta C, Sola R. Abnormalities of erythrocyte membrane fluidity, lipid composition, and lipid peroxidation in systemic sclerosis:evidence of free radical mediated-injury. Arthritis Rheum 2000;43:894-900
  • 16. Stein CM, Tanner SB, Award JA. Evidence of free radical mediated injury (isoprostane overproduction) in scleroderma. Arthritis Rheum 1996;39:1146-50
  • 17 Cracowski JL, Marpeau C, Carpentier PH. Enhanced in vivo lipid peroxidation in scleroderma spectrum disorders. Arthritis Rheum 2001;44:1143-8
  • 18. Cracowski JL, Carpentier Ph, Imbert B. Increased urinary F2-isoprostanes in systemic sclerosis, but not in primary Raynaud’s Phenomenon. Arhritis Rheum 2002;46:1319-23
  • 19. Rottoli P, Magi B, Cianti R, Bargagli E, Va-gaggini C, Nikiforakis N, et al. Carbonylated proteins in bronchoalveolar lavage of patients with sarcoidosis, pulmonary fibrosis associated with systemic sclerosis and idiopathic pulmonary fibrosis. Proteomics 2005;5:2612-18
  • 20. İyidir ÖT, Erten S. Bağ dokusu hastalıklarında otoantikorların klinikte kullanımı. Clinical evaluation of autoantibodies in connective tissue disorders. Türkiye Klinikleri J Med Sci 2007, 27:236-246
  • 21. Lau AT, He QY, Chiu JF. A proteome analysis of the arsenite response in cultured lung cells: evidence for in vitro oxidative stress-induced apoptosis. Biochem. J. 2004; 382:641-50
  • 22. Montuschi P, Ciabattoni G, Paredi P. 8-iso-prostane as a biomarker of oxidative stress in interstitial lung diseases. Am J Resp Crit Care Med 1998;158:1524-7
  • 23. Caramaschi P, Martinelli N, Biasi D, Carletto A, Faccini G, Volpe A, et al. Homocysteine plasma concentration is related to lung impairment in scleroderma. Journal of Rheu- matology 2003;30:298-304
  • 24. Cope KA, Solga SF, Hummers LK, Wigley FM, Diehl AM, Risby TH. Abnormal exhaled ethane concentrations in scleroderma. Biomarkers 2006; 11(1):70-84
  • 25. Simonini G, Cerinic MM, Generini S, Zoppi M, Anichini M, Cesaretti C, Pignone A, Fal-cini F, Lotti T, Cagnoni M. Oxidative stress in systemic sclerosis. Mol Cell Biochem 1999;196:85-91
  • 26. Granger DN, Rutili G, Mccord JM. Superoxide radicals in feline intestinal ischemia. Gastroenterology 1981 ;81:22-9
  • 27. Bulkley GB. Reactive oxygen metabolites and reperfusion injury: Aberrant triggerin of reticuloendothelial function. Lancet 1994;344:934-6
  • 28 Denton CP, Bickerstaff MCM, Shiwen X. Serial circulating adhesion molecule levels reflect disease severity in systemic sclerosis. Br J Rheumatol 1995;34:1048-54
  • 29. Bland AD, Herrick A, Jayson MIV. Altered levels of soluble adhesion molecules in rheumatoid arhritis, vasculitis and systemic sclerosis. Br J Rheumatol 1995;34:814-9
  • 30. Anderson GN, Caidahl K, Kazzam E. Correlation between increased nitric oxide production and markers of endothelial activation in systemic sclerosis. Arhritis Rheum 2000;43:1085-93
  • 31. Mcinnes IB, Leung BP, Field M, Wei XO. Production of nitric oxide in the synovial membrane of rheumatoid and osteoarthritis patients. J Exp Med 1996;184:1519-24
  • 32. Yamamoto T, Sawada Y, Katayama I, Nishioka K. Increased production of nitric oxide stimulated by interleukin-1 b in peripheral blood mononuclear cells in patients with systemic sclerosis. Br J Rheum 1998;37:1123-5
  • 33. Cavallo G, Sabadini L, Rollo L. Nitric oxide synthesis in peripheral blood mononuclear and polymorphonuclear cells from patients with systemic sclerosis. Rheumatology 1999;38:1301-4
  • 34. Matucci Cerinic M, Generini S, Pignone A, Cagnoni M. From Raynaud’s phenomenon to systemic sclerosis (scleroderma). Lack or exhaustion of adaptation? Ad Organ Biol 1998;6:241-53
  • 35. Housset E, Emerit I, Baulon A, De Grouchy J. Anomalies chromosomiques dans la scle-rodermie generalisee. Etude de dix malades. CR Acad Sci (Paris) 1969;269:413-19
  • 36. Peng SL, Fatenejad S, Craft J. Scleroderma:A disease related to damaged proteins? Nature Med 1997;3:276-8
  • 37. Halliwell B, Chirico S. Lipid peroxidation: Its mechanism, measurement, and significance. Am J Clin Nut 1993;57(suppl.):715-25
  • 38. Witztum JL, Steinberg D. Role of oxidised low density lipoprotein in atherogenesis. J Clin Invest 1991;88:1785-92
  • 39. Herrick AL, Illingworth KJ; Hollis S, Gomez-Zumaquero JM, Tinahones FJ: Antibodies against oxidised low density lipoproteins in systemic sclerosis. Rheumatology (Oxford) 2001;40(4):401-5
  • 40. Ingrassia TS, Ryu JH, Trastek VF, Rosenow EC. Oxygen exacerbated bleomycin pulmonary toxicity. Mayo Clin Oroc 1991;66:173-8
  • 41. Yoshida SH, German JB, Fletcher MP, Gershwin ME. The toxic oil syndrome: A perspective on immunotoxicologic mechanisms. Regul Toxicol Pharmacol 1994 Feb;19(1):60-79
  • 42. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 2nd ed. Oxford:Clarendon press; 1989. p.89
  • 43. Halliwell B, Gutteridge JMC, Cross CE. Free radicals, antioxidants and human disease: where are now? J Lab Clin Med 1992;119:589-620
  • 44. Wayner DDM, Burton GW, Ingold KU, Barclay LRC, Locke SJ. The relative contributions of vitamin E, urate, ascorbate and proteins to the peroxylradical trapping capacity of human blood plasma. Biochem Biophys Acta 1987;924:408-19
  • 45. Burton GW, Traber MG. Vitamin E: antioxidant activity, biokinetics and bioavailability. Ann Rev Nutr 1990;10:281-5
  • 46. Halliwell B, Grootveld M. The measurement of free radical reactions in humans. Some thoughts for future experimentation. FEBS Lett 1987;213:9-14
  • 47. Cranfield LM, Gollan JL, White AG, Doman-dy TL. Serum antioxidant activity in normal and abnormal subjects. Ann Clin Biochem 1979 Nov;16(6):299-306
  • 48. Me Quaid KE, Keenan AK. Endothelial barrier dysfunction and oxidative stress: roles for nitric oxide? Exp Physiol 1997;82:369-76
  • 49. Kaneko M, Hayashi J, Sato I, Miyasaka N. Probukol downregulates E-selectin expression on cultured human vascular endpthe-lial cells. Arterioscler Thromb Vase Biol 1996;16:1047-51
  • 50. Keaney JF, Xu A, Cunningham D, Jackson T, Frei B, Vita JA. Dietary probucol deserves endothelial functions in cholesterol-fed rabbits by limiting vascular oxidative stress and superoxide generation. J Clin Invest 1995;95:2520-9
  • 51. Reither RJ. Oxidative damage in the central nervous system: protection by melatonin. Prog Neurobiol 1998;56:359-84
  • 52. Reiter RJ, Tan DX, Cabrera J, et al. The oxi-dant/antioxidant network: role of melatonin. Biol Signals Recept 1999;8:56-63
  • 53. Wayne MC, Hazel SJ, Coull BM. Lazaroids. Drugs 1995;50:863-971
  • 54. Del Maestro RF, Thaw HH, Bjork J. Free radicals as mediators of tissue injury. Acta Physiol Scand 1980,492:43-57
There are 54 citations in total.

Details

Primary Language Turkish
Subjects Rheumatology and Arthritis
Journal Section Reviews
Authors

Şükran Erten

Publication Date July 25, 2010
Published in Issue Year 2010 Volume: 4 Issue: 2

Cite

APA Erten, Ş. (2010). SİSTEMİK SKLEROZDA OKSİDATİF STRES. Türk Tıp Dergisi, 4(2), 90-96.
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