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Etanercept reduces the oxidative stress marker levels in patients with rheumatoid arthritis

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Abstract

This study was performed to evaluate the effects of the TNF-α inhibitor etanercept on oxidation stress markers representing DNA damage, lipid peroxidation, and protein glycosylation. Twenty-two rheumatoid arthritis (RA) patients underwent etanercept treatment. The levels of serum total, urinary total, and urinary free pentosidine, which is an advanced glycation end-product (AGE), of urinary Nε-hexanoyl lysine (Nε-HEL), and of 8-hydroxy-deoxy guanosine (8-OHdG) were measured at baseline and at 3 and 6 months after the initial treatment with etanercept. Serum total and urinary total pentosidine levels were reduced at 6 months after the initial treatment with etanercept, and urinary free pentosidine levels were reduced at 3 and 6 months. Urinary Nε-HEL levels were also reduced at 3 and 6 months, and urinary 8-OHdG levels were reduced at 6 months. Serum total and urinary total pentosidine levels in RA patients correlated with the number of swelling joints and tender joints, and urinary total pentosidine levels correlated with the Disease Activity Score using 28 joints (DAS28). This study demonstrated that etanercept acts as a regulator against pentosidine formation, oxidative DNA damage, and lipid peroxidation in RA patients.

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References

  1. Hitchon CA, El-Gabalawy HS (2004) Oxidation in rheumatoid arthritis. Arthritis Res Ther 6:265–278

    Article  PubMed  Google Scholar 

  2. Halliwell B (1995) Oxygen radicals, nitric oxide and human inflammatory joint disease. Ann Rheum Dis 54:505–510

    PubMed  CAS  Google Scholar 

  3. Biemond P, Swaak AJ, Koster JF (1984) Protective factors against oxygen free radicals and hydrogen peroxide in rheumatoid arthritis synovial fluid. Arthritis Rheum 27:760–765

    Article  PubMed  CAS  Google Scholar 

  4. Woo CH, Kim TH, Choi JA, et al (2006) Inhibition of receptor internalization attenuates the TNF alpha-induced ROS generation in non-phagocytic cells. Biochem Biophys Res Commun 351:972–978

    Article  PubMed  CAS  Google Scholar 

  5. Sakon S, Xue X, Takekawa M et al (2003) NF-kappaB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. EMBO J 22:3898–3909

    Article  PubMed  CAS  Google Scholar 

  6. Takahashi M, Ohishi T, Aoshima H, Kawana K, Kushida K, Inoue T, Horiuchi K (1993) The Maillard protein cross-link pentosidine in urine from diabetic patients. Diabetologia 36:664–667

    Article  PubMed  CAS  Google Scholar 

  7. Jikimoto T, Nishikubo Y, Koshiba M, et al (2002) Thioredoxin as a biomarker for oxidative stress in patients with rheumatoid arthritis. Mol Immunol 38:765–772

    Article  PubMed  CAS  Google Scholar 

  8. Mitoma H, Horiuchi T, Hatta N, Tsukamoto H, Harashima S, Kikuchi Y, Otsuka J, Okamura S, Fujita S, Harada M (2005) Infliximab induces potent anti-inflammatory responses by outside-to-inside signals through transmembrane TNF-alpha. Gastroenterology 128:376–392

    Article  PubMed  CAS  Google Scholar 

  9. Van den Brande JM, Braat H, van den Brink GR, Versteeg HH, Bauer CA, Hoedemaeker I, van Montfrans C, Hommes DW, Peppelenbosch MP, van Deventer SJ (2003) Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn’s disease. Gastroenterology 124:1774–1785

    Article  PubMed  CAS  Google Scholar 

  10. Lugering A, Schmidt M, Lugering N, Pauels HG, Domschke W, Kucharzik T (2001) Infliximab induces apoptosis in monocytes from patients with chronic active Crohn’s disease by using a caspase-dependent pathway. Gastroenterology 121:1145–1157

    Article  PubMed  CAS  Google Scholar 

  11. Rall LC, Roubenoff R, Meydani SN, Han SN, Meydani M (2000) Urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG) as a marker of oxidative stress in rheumatoid arthritis and aging: effect of progressive resistance training. J Nutr Biochem 11:581–584

    Article  PubMed  CAS  Google Scholar 

  12. Jaswal S, Mehta HC, Sood AK, Kaur J (2003) Antioxidant status in rheumatoid arthritis and role of antioxidant therapy. Clin Chim Acta 338:123–129

    Article  PubMed  CAS  Google Scholar 

  13. Kato Y, Mori Y, Makino Y, Morimitsu Y, Hiroi S, Ishikawa T, Osawa T (1999) Formation of Nepsilon-(hexanonyl)lysine in protein exposed to lipid hydroperoxide. A plausible marker for lipid hydroperoxide-derived protein modification. J Biol Chem 274:20406–20414

    Article  PubMed  CAS  Google Scholar 

  14. Winrow VR, Winyard PG, Morris CJ, Blake DR (1993) Free radicals in inflammation: second messengers and mediators of tissue destruction. Br Med Bull 49:506–522

    PubMed  CAS  Google Scholar 

  15. Mapp PI, Grootveld MC, Blake DR (1995) Hypoxia, oxidative stress and rheumatoid arthritis. Br Med Bull 51:419–436

    PubMed  CAS  Google Scholar 

  16. Kumar DA, Raju KV, Settu K, Kumanan K, Puvanakrishnan R (2006) Effect of a derivatized tetrapeptide from lactoferrin on nitric oxide mediated matrix metalloproteinase-2 production by synovial fibroblasts in collagen-induced arthritis in rats. Peptides 27:1434–1442

    Article  PubMed  CAS  Google Scholar 

  17. Bates EJ, Johnson CC, Lowther DA (1985) Inhibition of proteoglycan synthesis by hydrogen peroxide in cultured bovine articular cartilage. Biochim Biophys Acta 838:221–228

    PubMed  CAS  Google Scholar 

  18. Baker MS, Bolis S, Lowther DA (1991) Oxidation of articular cartilage glyceraldehyde-3-phosphate dehydrogenase (G3PDH) occurs in vivo during carrageenin-induced arthritis. Agents Actions 32:299–304

    Article  PubMed  CAS  Google Scholar 

  19. Schalkwijk J, van den Berg WB, van de Putte LB, Joosten LA (1986) An experimental model for hydrogen peroxide-induced tissue damage. Effects of a single inflammatory mediator on (peri)articular tissues. Arthritis Rheum 29:532–538

    Article  PubMed  CAS  Google Scholar 

  20. Garrett IR, Boyce BF, Oreffo RO, Bonewald L, Poser J, Mundy GR (1990) Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J Clin Invest 85:632–639

    PubMed  CAS  Google Scholar 

  21. Bax BE, Alam AS, Banerji B et al (1992) Stimulation of osteoclastic bone resorption by hydrogen peroxide. Biochem Biophys Res Commun 183:1153–1158

    Article  PubMed  CAS  Google Scholar 

  22. Bonizzi G, Piette J, Merville MP, Bours V (2000) Cell type-specific role for reactive oxygen species in nuclear factor-κB activation by interleukin-1. Biochem Pharmacol 59:7–11

    Article  PubMed  CAS  Google Scholar 

  23. Bonizzi G, Piette J, Schoonbroodt S, Greimers R, Havard L, Merville MP, Bours V (1999) Reactive oxygen intermediate-dependent NF-kappaB activation by interleukin-1beta requires 5-lipoxygenase or NADPH oxidase activity. Mol Cell Biol 19:1950–1960

    PubMed  CAS  Google Scholar 

  24. Jacquier-Sarlin MR, Jornot L, Polla BS (1995) Differential expression and regulation of hsp70 and hsp90 by phorbol esters and heat shock. J Biol Chem 270:14094–14099

    Article  PubMed  CAS  Google Scholar 

  25. Sung JY, Hong JH, Kang HS, Choi I, Lim SD, Lee JK, Seok JH, Lee JH, Hur GM (2000) Methotrexate suppresses the interleukin-6 induced generation of reactive oxygen species in the synoviocytes of rheumatoid arthritis. Immunopharmacology 47:35–44

    Article  PubMed  CAS  Google Scholar 

  26. Miesel R, Murphy MP, Kroger H (1996) Enhanced mitochondrial radical production in patients which rheumatoid arthritis correlates with elevated levels of tumor necrosis factor alpha in plasma. Free Radic Res 25:161–169

    Article  PubMed  CAS  Google Scholar 

  27. Mur E, Zabernigg A, Hilbe W, Eisterer W, Halder W, Thaler J (1997) Oxidative burst of neutrophils in patients with rheumatoid arthritis: influence of various cytokines and medication. Clin Exp Rheumatol 15:233–237

    PubMed  CAS  Google Scholar 

  28. den Broedr AA (2003) Neutrophil migration and production of reactive oxygen species during treatment with a fully human anti-tumor necrosis factor-alpha monoclonal antibody in patients with rheumatoid arthritis. J Rheumatol 30:232–237

    Google Scholar 

  29. Kirchner S, Holler E, Haffner S, Andreesen R, Eissner G (2004) Effect of different tumor necrosis factor (TNF) reactive agents on reverse signaling of membrane integrated TNF in monocytes. Cytokine 28:67–74

    Article  PubMed  CAS  Google Scholar 

  30. Sieper J, Van Den Brande J (2005) Diverse effects of infliximab and etanercept on T lymphocytes. Semin Arthritis Rheum 34(Suppl1):23–27

    Article  PubMed  CAS  Google Scholar 

  31. Halliwell B, Hoult JR, Blake DR (1988) Oxidants, inflammation, and anti-inflammatory drugs. FASEB J 2:2867–2873

    PubMed  CAS  Google Scholar 

  32. Takahashi M (2006) Pentosidine, an advanced glycation endproduct, and arthritis. Curr Rheumatol Rev 2:319–324

    Article  CAS  Google Scholar 

  33. Erhola M, Toyokuni S, Okada K, Tanaka T, Hiai H, Ochi H, Uchida K, Osawa T, Nieminen MM, Alho H, Kellokumpu-Lehtinen P (1997) Biomarker evidence of DNA oxidation in lung cancer patients: association of urinary 8-hydroxy-2’-deoxyguanosine excretion with radiotherapy, chemotherapy, and response to treatment. FEBS Lett 409:287–291

    Article  PubMed  CAS  Google Scholar 

  34. Rodriguez-Garcia J, Requena JR, Rodriguez-Segade S (1998) Increased concentrations of serum pentosidine in rheumatoid arthritis. Clin Chem 44:250–255

    PubMed  CAS  Google Scholar 

  35. Takahashi M, Kushida K, Ohishi T et al (1994) Quantitative analysis of crosslinks pyridinoline and pentosidine in articular cartilage of patients with bone and joint disorders. Arthritis Rheum 37:724–728

    Article  PubMed  CAS  Google Scholar 

  36. Verzijl N, DeGroot J, Bank RA, Bayliss MT, Bijlsma JW, Lafeber FP, Maroudas A, TeKoppele JM. (2001) Age-related accumulation of the advanced glycation endproduct pentosidine in human articular cartilage aggrecan: the use of pentosidine levels as a quantitative measure of protein turnover. Matrix Biol 20:409–417

    Article  PubMed  CAS  Google Scholar 

  37. Takahashi M, Suzuki M, Kushida K, Miyamoto S, Inoue T (1997) Relationship between pentosidine levels in serum and urine and activity in rheumatoid arthritis. Br J Rheumatol 36:637–642

    Article  PubMed  CAS  Google Scholar 

  38. Schraufstatter IU, Hyslop PA, Jackson JH, Cochrane CG (1988) Oxidant-induced DNA damage of target cells. J Clin Invest 82:1040–1050

    PubMed  CAS  Google Scholar 

  39. Kasai H, Crain PF, Kuchino Y, Nishimura S, Ootsuyama A, Tanooka H (1986) Formation of 8-hydroxyguanine moiety in cellular DNA by agents producing oxygen radicals and evidence for its repair. Carcinogenesis (Lond) 7:1849–1851

    Article  CAS  Google Scholar 

  40. Toyokuni S (1999) Reactive oxygen species-induced molecular damage and its application in pathology. Pathol Int 49:91–102

    Article  PubMed  CAS  Google Scholar 

  41. Honda M, Yamada Y, Tomonaga M, Ichinose H, Kamihira S (2000) Correlation of urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, and clinical features of hematological disorders: a pilot study. Leuk Res 24:461–468

    Article  PubMed  CAS  Google Scholar 

  42. Kim JY, Mukherjee S, Ngo LC, Christiani DC (2004) Urinary 8-hydroxy-2’-deoxyguanosine as a biomarker of oxidative DNA damage in workers exposed to fine particulates. Environ Health Perspect 112:666–671

    Article  PubMed  CAS  Google Scholar 

  43. Kato Y, Mori Y, Makino Y, Morimitsu Y, Hiroi S, Ishikawa T, Osawa T (1999) Formation of Nepsilon-(hexanonyl)lysine in protein exposed to lipid hydroperoxide. A plausible marker for lipid hydroperoxide-derived protein modification. J Biol Chem 274:20406–20414

    Article  PubMed  CAS  Google Scholar 

  44. Kato Y, Yoshida A, Naito M, Kawai Y, Tsuji K, Kitamura M, Kitamoto N, Osawa T (2004) Identification and quantification of N(epsilon)-(Hexanoyl)lysine in human urine by liquid chromatography/tandem mass spectrometry. Free Radic Biol Med 37:1864–1874

    Article  PubMed  CAS  Google Scholar 

  45. Thannickal VJ, Fanburg BL (2000) Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol 279:1005–1028

    Google Scholar 

  46. Thabrew MI, Senaratna L, Samarawickrema N, Munasinghe C (2001) Antioxidant potential of two polyherbal preparations used in Ayurveda for the treatment of rheumatoid arthritis. J Ethnopharmacol 76:285–291

    Article  PubMed  CAS  Google Scholar 

  47. Halliwell B (1994) Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 344:721–724

    Article  PubMed  CAS  Google Scholar 

  48. Bae SC, Kim SJ, Sung MK (2003) Inadequate antioxidant nutrient intake and altered plasma antioxidant status of rheumatoid arthritis patients. J Am Coll Nutr 22:311–315

    PubMed  CAS  Google Scholar 

  49. Kamanli A, Naziroglu M, Aydilek N, Hacievliyagil C (2004) Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid arthritis. Cell Biochem Funct 22:53–57

    Article  PubMed  CAS  Google Scholar 

  50. Araujo V, Arnal C, Boronat M, Ruiz E, Dominguez C (1998 ) Oxidant-antioxidant imbalance in blood of children with juvenile rheumatoid arthritis. Biofactors 8:155–159

    PubMed  CAS  Google Scholar 

  51. Karatas F, Ozates I, Canatan H, Halifeoglu I, Karatepe M, Colakt R (2003) Antioxidant status & lipid peroxidation in patients with rheumatoid arthritis. Indian J Med Res 118:178–181

    PubMed  CAS  Google Scholar 

  52. Cao G, Prior RL (1998) Comparison of different analytical methods for assessing total antioxidant capacity of human serum. Clin Chem 44:1309–1325

    PubMed  CAS  Google Scholar 

  53. Wang CC, Chu CY, Chu KO, Choy KW, Khaw KS, Rogers MS, Pang CP (2004) Trolox-equivalent antioxidant capacity assay versus oxygen radical absorbance capacity assay in plasma. Clin Chem 50:952–954

    Article  PubMed  CAS  Google Scholar 

  54. Schofield D, Braganza JM (1996) Shortcomings of an automated assay for total antioxidant status in biological fluids. Clin Chem 42:1712–1714

    PubMed  CAS  Google Scholar 

  55. Lamont J, Campbell J, FitzGerald P. (1997) Measurement of individual vs total antioxidants. Clin Chem 43:852–854

    PubMed  CAS  Google Scholar 

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Acknowledgments

In this study, I wish to express my gratitude to the offer of patient’s data for the orthopedics clinic of Shimazu (Sizuoka, Japan).

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3125, Japan

    Yasunori Kageyama, Masaaki Takahashi, Tetsuyuki Nagafusa, Eiji Torikai & Akira Nagano

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  1. Yasunori Kageyama
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  2. Masaaki Takahashi
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  3. Tetsuyuki Nagafusa
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  4. Eiji Torikai
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Correspondence to Yasunori Kageyama.

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Kageyama, Y., Takahashi, M., Nagafusa, T. et al. Etanercept reduces the oxidative stress marker levels in patients with rheumatoid arthritis. Rheumatol Int 28, 245–251 (2008). https://doi.org/10.1007/s00296-007-0419-1

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  • DOI: https://doi.org/10.1007/s00296-007-0419-1

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