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Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia: etiologic and therapeutic concerns


We proposed to assess the oxidant/antioxidant status, lipid peroxidation and nitric oxide (NO) in untreated fibromyalgia (FM) patients and controls. The effect of amitriptyline (A, 20 mg daily) and sertraline (S, 100 mg daily) treatment on patients’ superoxide dismutase (SOD), xanthine oxidase (XO), adenosine deaminase (ADA) enzyme activities, thiobarbituric acid reactive substances (TBARS) and NO levels was investigated. Thirty female patients with primary FM and age-matched 16 healthy female controls were included. Patients received an 8-week course of treatment with either A or S. FM patients had higher serum levels of TBARS (particularly malondialdehyde) and lower levels of nitrite compared to controls whereas enzyme activities were similar. A and S significantly improved Fibromyalgia Impact Questionnaire (FIQ) pain scores, Hamilton anxiety and depression rating scales. But neither A nor S had significant effects on measured oxidative stress parameters, except SOD activity that was significantly reduced after S treatment. Total myalgic scores negatively correlated with XO activity, and depression scales negatively correlated with levels of TBARS. Our results indicate that patients with FM are under oxidative stress. These findings represent a rationale for further research assessing the effect of free radical scavengers or antioxidant agents like vitamins and omega-3 fatty acids on peripheral and central mechanisms in FM.

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Fig. 1
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Nitric oxide






Superoxide dismutase


Xanthine oxidase


Adenosine deaminase


Thiobarbituric acid reactive substances


Fibromyalgia Impact Questionnaire


Reactive oxygen species


Chronic fatigue syndrome

O2 :



Nitric oxide synthase


Pain pressure threshold


Hamilton Depression Rating Scale


Hamilton Anxiety Rating Scale


Polyunsaturated fatty acids


Nitroblue tetrazolium





NO 2 :


NO. :

Nitric oxide radical


  1. Goldenberg DL (1999) Fibromyalgia syndrome a decade later. What have we learned? Arch Intern Med 159:777–785

    Article  PubMed  CAS  Google Scholar 

  2. Cofford LJ, Appleton BE (2000) The treatment of fibromyalgia: a review of clinical trials. Curr Rheum Rep 2:101–103

    Article  Google Scholar 

  3. Akyol O, Isci N, Temel I, Ozgocmen S, Uz E, Murat M, Buyukberber S (2001) The relationships between plasma and erythrocyte antioxidant enzymes and lipid peroxidation in patients with rheumatoid arthritis. Joint Bone Spine 68:311–317

    Article  Google Scholar 

  4. Ozgocmen S, Sogut S, Ardicoglu O, Fadillioglu E, Pekkutucu I, Akyol O (2004) Serum nitric oxide, catalase, superoxide dismutase, and malondialdehyde status in patients with ankylosing spondylitis. Rheumatol Int 24:80–83

    Article  PubMed  CAS  Google Scholar 

  5. Keenoy BM, Moorkens G, Vertommen J, Leeuw ID (2001) Antioxidant status and lipoprotein in chronic fatigue syndrome. Life Sci 68:2037–2049

    Article  PubMed  Google Scholar 

  6. Vecchiet J, Capillone F, Falasca K, Mezzetti A, Pizzigallo E, Bucciarelli T, De Laurentis S, Affaitati G, De Cesare D, Giamberardino MA (2004) Relationship between musculoskeletal symptoms and blood markers of oxidative stress in patients with chronic fatigue syndrome. Neurosci Lett 335:151–154

    Article  Google Scholar 

  7. Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11:81–128

    Article  PubMed  CAS  Google Scholar 

  8. Sogut S, Zoroglu S, Ozyurt H, Yilmaz HR, Ozugurlu F, Sivasli E, Yetkin O, Yanik M, Tutkun H, Savas HA, Tarakcioglu M, Akyol O (2003) Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin Chim Acta 331:111–117

    Article  PubMed  CAS  Google Scholar 

  9. Kigwell BA (2000) Nitric oxide-mediated metabolic regulation during exercise: effect of training in health and cardiovascular disease. FASEB J 14:1685–1696

    Article  PubMed  Google Scholar 

  10. Akyol O, Zoroglu SS, Armutcu F, Sahin S, Gurel A (2004) Nitric oxide as a physiopathological factor in neuropsychiatric disorders. In Vivo 18:377–390

    PubMed  CAS  Google Scholar 

  11. Cepinskas G, Rui T, Kvietys PR (2002) Interaction between reactive oxygen metabolites and nitric oxide in oxidant tolerance. Free Radic Biol Med 33:433–440

    PubMed  Article  CAS  Google Scholar 

  12. Larson AA, Giovengo SL, Russell IJ, Michalek JE (2000) Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways. Pain 87:201–211

    Article  PubMed  CAS  Google Scholar 

  13. Wolfe F, Smythe HA, Yunus MB, Bennet RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P (1990) The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Arthritis Rheum 33:160–172

    PubMed  Article  CAS  Google Scholar 

  14. Catal SA, Erdem HR, Okumus M, Ozgocmen S, Yorgancioglu ZR (2000) The measurement of pain pressure threshold in patients with rheumatoid arthritis. Pain Clin 12:187–191

    Article  Google Scholar 

  15. Okifuji A, Turk DC, Sinclair D, Starz TW, Marcus DA (1997) A standardized manual tender point survey. I. Development and determination of a threshold point for the identification of positive tender points in fibromyalgia syndrome. J Rheumatol 24:377–383

    PubMed  CAS  Google Scholar 

  16. Ozgocmen S, Yoldas T, Kamanli A, Yildizhan H, Yigiter R, Ardicoglu O (2003) Auditory P300 event related potentials and serotonin reuptake inhibitor treatment in patients with fibromyalgia. Ann Rheum Dis 62:551–555

    Article  PubMed  CAS  Google Scholar 

  17. Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    PubMed  CAS  Article  Google Scholar 

  18. Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55

    PubMed  CAS  Google Scholar 

  19. Sarmer S, Ergin S, Yavuzer G (2000) The validity and reliability of the Turkish version of the Fibromyalgia Impact Questionnaire. Rheumatol Int 20:9–12

    Article  PubMed  CAS  Google Scholar 

  20. Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. In: Packer L, Glazer AN (eds) Oxygen radicals in biological systems, Methods Enzymol. Academic Press, California, 186:407–421

  21. Cortas NK, Wakid NW (1990) Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 36:1440–1443

    PubMed  CAS  Google Scholar 

  22. Sun Y, Oberley LW, Li Y (1988) A simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500

    PubMed  CAS  Google Scholar 

  23. Prajda N, Weber G (1975) Malign transformation-linked imbalance: decreased XO activity in hepatomas. FEBS Lett 59:245–249

    Article  PubMed  CAS  Google Scholar 

  24. Giusti G (1974) Adenosine deaminase. In: Bergmeyer MV (ed) Methods of enzymatic analysis, 2nd edn. Academic Press, New York, pp. 1092–1098

    Google Scholar 

  25. Eisinger J, Gandolfo C, Zakarian H, Ayavou T (1997) Reactive oxygen species, antioxidant status and fibromyalgia. J Musculoskeletal Pain 5:5–15

    Article  Google Scholar 

  26. Lund N, Bengtsson A, Thorborg P (1986) Muscle oxygen tissue pressure in primary fibromyalgia. Scand J Rheumatol 15:165–173

    PubMed  Article  CAS  Google Scholar 

  27. Bennett RM, Clark SR, Goldberg L, Nelson D, Bonafede RP, Porter J, Specht D (1989) Aerobic fitness in patients with fibrositis. A controlled study of respiratory gas exchange and 133xenon clearance from exercising muscle. Arthritis Rheum 32:454–460

    PubMed  Article  CAS  Google Scholar 

  28. Hein G, Franke S (2002) Are advanced glycation end-product-modified proteins of pathogenetic importance in fibromyalgia? Rheumatology 41:1163–1167

    Article  PubMed  CAS  Google Scholar 

  29. Lindh MH, Johansson LG, Hedberg M, Henning GB, Grimby G (1995) Muscle fiber characteristics, capillaries and enzymes in patients with fibromyalgia and controls. Scand J Rheumatol 24:34–37

    PubMed  Article  CAS  Google Scholar 

  30. Jeschonneck M, Graohmann G, Hein G, Sprott H (2000) Abnormal microcirculation and temperature in skin above tender points in patients with fibromyalgia. Rheumatology 39:917–921

    Article  PubMed  CAS  Google Scholar 

  31. Fulle S, Mecocci P, Fano G, Vecchiet I, Vecchini A, Racciotti D, Cherubini A, Pizzigallo E, Vecchiet L, Senin U, Beal MF (2000) Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome. Free Radic Biol Med 29:1252–1259

    Article  PubMed  CAS  Google Scholar 

  32. Sackner MA, Gummels EM, Adams JA (2004) Say NO to fibromyalgia and chronic fatigue syndrome: an alternative and complementary therapy to aerobic exercise. Med Hypotheses 63:118–123

    Article  PubMed  CAS  Google Scholar 

  33. Bagis S, Tamer L, Sahin G, Bilgin R, Guler H, Ercan B, Erdogan C (2005) Free radicals and antioxidants in primary fibromyalgia: an oxidative stress disorder? Rheumatol Int 25:188–190

    Article  PubMed  CAS  Google Scholar 

  34. Bilici M, Efe H, Koroglu MA, Uydu HA, Bekaroglu M, Deger O (2001) Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord 64:43–51

    Article  PubMed  CAS  Google Scholar 

  35. Park DC, Glass JM, Minear M, Crofford LJ (2001) Cognitive function in fibromyalgia patients. Arthritis Rheum 44:2125–2133

    Article  PubMed  CAS  Google Scholar 

  36. Delibas N, Ozcankaya R, Altuntas I (2002) Clinical importance of erythrocyte malondialdehyde levels as a marker of cognitive deterioration in patients with dementia of Alzheimer type: a repeated study in 5-year interval. Clin Biochem 32:137–141

    Article  Google Scholar 

  37. Merchant RE, Carmack CA, Wise CM (2000) Nutritional supplementation with Chlorella pyrenoidosa for patients with fibromyalgia syndrome: a pilot study. Phytother Res 14:167–173

    Article  PubMed  CAS  Google Scholar 

  38. Ozgocmen S, Catal SA, Ardicoglu O, Kamanli A (2000) Effect of omega-3 fatty acids in the management of fibromyalgia syndrome. Int J Clin Pharmacol Ther 38:362–363

    PubMed  CAS  Google Scholar 

  39. Hostmark AT, Lystad E, Vellar OD, Hovi K, Berg JE (1993) Reduced plasma fibrinogen, serum peroxides, lipids, and apolipoproteins after a 3-week vegetarian diet. Plant Foods Hum Nutr 43:55–61

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Salih Ozgocmen.

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Ozgocmen, S., Ozyurt, H., Sogut, S. et al. Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia: etiologic and therapeutic concerns. Rheumatol Int 26, 598–603 (2006).

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  • Fibromyalgia
  • Superoxide dismutase
  • Lipid peroxidation
  • Nitric oxide
  • Oxidative stress