Antioxidant Enzymes in Rheumatoid Arthritis

Journal of Arthritis

ISSN - 2167-7921

Research Article - (2016) Volume 0, Issue 0

Antioxidant Enzymes in Rheumatoid Arthritis

Vivek Kumar1,3, Jaya Prakash2, Varsha Gupta1* and Khan MY3
1Rheumatology Laboratory, Department of Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur, India
2Community Health Centre, Shivrajpur, Kanpur, India
3Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India
*Corresponding Author: Varsha Gupta, Rheumatology Laboratory, Department of Biotechnology, Chhatrapati Shahu Ji Maharaj University, Kanpur, Uttar Pradesh, India, Tel: 09450442861, Fax: +91-512-2570006 Email:


Joint destruction in rheumatoid arthritis (RA) is due to tissue injury in the area caused by inflammatory reactions, release of MMPs and free radicals produced by neutrophils and macrophages. The control of free radical production may have therapeutic roles thus the study was done to check the status of lipid peroxidation product malondialdehyde (MDA) and a few antioxidant enzymes in RA patients. 45 RA patients and 40 controls were selected. Controls were asymptomatic and RA patients were selected according to ACR criteria. RA patients had significantly high MDA, SOD and ALP and reduced activity of catalase and GR as compared to controls. SOD showed positive correlation with ALP. GR was positively related with MDA, SOD and ALP. The study shows that MDA is involved in the pathogenesis of RA. The system is trying to quench free radicals by high SOD activity. Higher production of H2O2 or some other mechanism is responsible for inhibition of catalase and GR. However system is trying to reduce the damage by neutralizing superoxide anion. Therapeutic intervention of the oxidative stress may be considered for effective control of inflammation in RA patients.

Keywords: Malondialdehyde; Superoxide anion; Superoxide dismutase; Catalase; Glutathione S-transferase


RA: Rheumatoid Arthritis; MDA: Malondialdehyde; SOD: Superoxide Dismutase; GST: Glutathione-S-Transferase


Rheumatoid arthritis (RA) is the inflammatory disease which leads to progressive destruction of multiple synovial joints [1]. T-cells and cytokines play an important role along with oxygen radicals as superoxide and hydrogen peroxide released by activated macrophages in the progression of rheumatoid arthritis [2]. These reactive oxygen species (ROS) and reactive nitrogen species (RNS) which are thus produced have both beneficial and toxic effects. Oxidative stress is the condition when concentration of ROS and RNS becomes deleterious and damage the cells and biological macromolecules [3,4] and thus the body. Oxidative stress occurs due to disturbed balance between body’s antioxidant mechanisms and oxidative stress production and has important role in the development of chronic disease as autoimmunity like RA, cancer etc. [5-7].

They are capable of damaging membrane lipids, connective tissue and nucleic acids of the cell. Free radicals and their byproducts are essential mediators of inflammation. Due to chemo-attractant property of synovial fluid, leukocytes accumulate with in the synovial tissue triggering a respiratory burst characterized by increased oxygen consumption and increased anaerobic glycolysis leading to generation of superoxide, hydroxyl, hypochloric radicals etc. [8]. Neutrophils have been shown to be very active in synovial fluid of patients with RA which leads to inflammation and damage [9,10].

In the body free radical generation and enzymes degrading them are in tight homeostasis which prevents damage. However, studies [11,12] show that enzymatic/non enzymatic antioxidant systems are highly deregulated and impaired in RA. Markers of protein and lipid oxidation have been found to be raised in arthritic animals. Therefore there are chances of free radical mediated damage to the body of RA patients due to their higher production or improper scavenging. Thus analysis of activities of different antioxidant enzymes like superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and glutathione reductase (GR) may have effective therapeutic potential [11,13,14]. There is more interest in roles of these in the clinical outcomes of disease like RA, therefore, we were interested in analyzing the level of MDA which is product of lipid peroxidation and level of enzymes of free radical scavenger system like superoxide dismutase (SOD), GR, catalase and levels of alkaline phosphatase (ALP) in RA patients treated with MTX, Folic acid Vit-C and occasional corticosteroids.

Materials and Methods

45 samples (30 females, 15 males) were randomly selected from the OPD of Orthopaedics from different centers during the study period. Patients were recruited who fulfilled 4 or above criteria of American College of Rheumatology (ACR) [15]. Out of 45 patients with RA, 38 were tested positive for RF factor and anti-cyclic citrullinated protein (CCP) antibody. 40 asymptomatic independent controls (24 females, 16 males) were recruited from local clubs, neighbourhood and volunteers. Controls were asymptomatic (painless, no criptation, no decrease of joint space on X-ray, nonobese and without any other systemic disease) and independent of the patients.

Patients were recommended MTX (15 mg once a week) along with folic acid (1 mg OD) and vitamin C to alleviate symptoms. Whenever the patient complaints about swelling with the existing treatment (usually at the change of season) the local corticosteroid (triamcinolone acetonide 0.5 ml) was given at the swollen joints. The usual requirement was 4-6 times/year. The patients did not had any renal disease and were non hypertensive. Blood was drawn from overnight fasting patients for all the analysis. The study was started after approval from Institutional ethical committee and written informed consent was obtained from all the patients.

Laboratory analysis

MDA which is an indicator of oxidative stress was measured by the production of thiobarbituric acid reactive compounds (TBARS) [16]. Glutathione reductase activity was measured following the oxidation of nicotinamide adenine dinucleotide phosphate reduced (NADPH) in the presence of oxidized glutathione (GSSG). SOD estimation was done according to Mishra and Fridovich, [17]. Catalase activity was analysed according to method of Sinha [18]. Glutathione reductase activity was done as describe by [19]. Alkaline phosphatase level was measured by COGENT Kit, Span Diagnostic Ltd.

Results and Discussion

In our study lipid per-oxidation in terms of MDA production was significantly increased in RA patients (Table 1) which may be due to increased ROS during chronic inflammation. Lipid peroxides are generated at the site of tissue injury due to inflammation and diffuses into blood and can be estimated in serum or plasma [20]. Studies [21-24] have reported raised levels of MDA in the serum, plasma and erythrocytes of RA patients. In our study SOD levels are highly increased (Table 1). Superoxides anion (O2-) has important role in pathogenesis of many diseases (7). It is neutralize by SOD to hydrogen peroxide (H2O2). H2O2 is further quenched by activity of catalase and glutathione peroxidase. Transformation of O2- to H2O2 prevents the formation of aggressive compound as peroxynitrile (ONOO-) and hydroxyl radical (OH-) [25]. The patients showed significantly higher activity of SOD and ALP (Table 1). There was strong positive correlation between SOD and ALP activity (Table 2). They showed reduced activities for catalase and glutathione reductase (Table 1). The GR activity was positively correlated to MDA, SOD and ALP (Table 2).

  Control Rheumatoid arthritis patients
  N=40 N=45
MDA 0.763 ± 0.02134 2.519 ± 0.11784 P**
SOD 484.96 ± 14.55467 1186.08 ± 31.87685 P**
Catalase 1.722 ± 0.0450 1.31 ± 0.0264 P**
GST 25.84 ± 0.7822 20.94 ± 0.3887 P**
ALP 151.17 ± 0.8482 182.86 ± 0.7321 P**

Table 1: The table shows the data for MDA, SOD, catalase, GST and ALP. The p is significant at *p<0.05, **p<0.01.

MDA 1        
SOD -0.049 1      
CATALASE -0.114 -0.111 1    
GST 0.328* 0.486** -0.01 1  
ALP -0.147 0.682** 0.001 0.326* 1

Table 2: Shows the correlation between various parameters in RA patients (N-45). The p is significant at *p<0.05, **p<0.01.

Reactive oxygen species and oxidative stress have a role in the pathogenesis of RA [22]. Free radicals and other reactive species play an important role of super oxidant leading to oxidation of biomolecules like proteins, amino acids, lipids and DNA [26], which are ultimately responsible for cell injury and death [27]. Prime targets of ROS attack are the polyunsaturated fatty acids in the membrane lipids causing lipid peroxidation (LPO) which may lead to disorganization of cell structure and function. Further decomposition of peroxidized lipids yields a wide variety of end-products, including malondialdehyde (MDA) [28]. Malon dialdehyde (MDA) is one of an important lipid peroxide which is high in RA patients [29,30]. Measurement of MDA is widely used as an indicator of LPO.

Many studies have reported high MDA in the serum, plasma and synovial fluid of RA patients [22,28,31]. MDA has an important role in pathogenesis of RA. There is growing awareness that reactive oxygen species and free radicals may play an important role in mediating cellular injury and tissue damage in rheumatoid arthritis. Thiele et al. [32] have reported malondialdehyde-acetaldehyde (MAA) adduct formation is increased in RA. They appear to result in robust antibody responses which are strongly associated with anti citrullinated protein antigens (ACPAs) suggesting that MAA formation may be a cofactor that drives tolerance loss, resulting in the autoimmune responses characteristic of RA.

Higher levels may be the result of respiratory burst triggered by leucocytes. A study has shown activation of neutrophilic myeloperoxidase-hydrogen peroxide system in RA synovial tissue which may contribute to cyclic self-perpetuating inflammation [10]. Methotrexate treatment has been reported to increase Zn-SOD activity but it has no effects on GSH-Px in rats [33,34].

But possibly increased activity of SOD [35,36] may be attributed to increased O2- production by hyperactive cells leading to SOD induction [37,38]. Another possibility may be excessive free radical production through the xanthine-xanthine oxidase system is the primary factors in RA, rather than an impaired antioxidant system [36]. Else higher SOD levels may be a change to nullify excessive free radical production. Post treatment the antioxidants are increased which lead to lower plasma MDA and increased total antioxidant capacity (TAC) [3,39].

However lower SOD has also been reported in patients with RA on MTX therapy in comparison with RA without MTX therapy [40]. It has also being observed that MTX can suppress directly or indirectly the generation of active oxygen metabolites induced by IL-6, which is produced in response to TNF-α stimulation in synovial cells of RA [41] as well as in polymorphnuclear cells. The increased levels serum Cu/Zn SOD may support the hypothesis of radical- mediated injury.

Over expression of extracellular SOD leads to dismutation of superoxide resulting in H2O2 accumulation. Analysis of H2O2 in different settings is being done and authors conclude, more SOD does not mean more H2O2 [42]. The formation of H2O2 due to dismutation of superoxide is limited by the amount of superoxide, not by the rate it is converted to H2O2. Accumulation of superoxide leads to the oxidation of NO forming peroxynitrite. There more H2O2 is unlikely to be toxic as this would amount to substituting a very mild cytokine (H2O2) for a potant (peroxynitrite) [43].

Decreased activity of SOD in RA patients has also been reported [44]. However our study is in line with [13,22] who have reported increased SOD levels in RA patients. Mazetti et al. [13] have reported higher serum copper/Zn superoxide in patients with RA. Igari et al. [45] have reported correlation between the overall synovial SOD activity and both the clinical severity of the disease and the CRP levels. Mazetti et al. [13] have concluded that exercise induced hypoxic reperfusion mechanism with in the inflamed joint in RA may lead to increased production of Cu/Zn SOD. Mateen et al. [46] have shown that increase of oxidative stress increases with the progression of RA.

H2O2 formed due to activity of superoxide dismutase need to be detoxified by glutathione peroxidase and catalase activity. Catalase plays an important role in preventing ROS mediated damage by using H2O2 and converting it to water and oxygen. In our RA patients, catalase activity is significantly decreased as compared to control. Lower catalasae activity may be due to interaction of catalase by hydrogen peroxide [44]. Lowered activities of their enzymes may lead to conversion of H2O2 to hydroxyl radical by iron released from hemoglobin of lysed erythrocytes [47]. However unaltered catalase activity in RA patients has been reported [48].

Catalase activity was not found in serum of RA patients. Decreased erythrocytes catalase activity is also being reported [47]. Our study is in accordance with 28,36 and shows lower catalase activity in serum of RA patients. Catalase expression affects expression of genes which influence inflammation [49]. Lower levels of catalase may be responsible for high inflammation in RA. Cimen et al. [36] have reported higher SOD activity and MDA levels and unchanged catalase and GSH-Px activities in RA patients. The study by Gonzalez et al. [50] observed the positive correlation between antioxidant GPx and lipid peroxidation levels. Their results suggest that GPx activity is involved in the primary mechanisms against oxidative stress in RA patients. Both GPx and catalase use H2O2 as substrate where catalase acts in the presence of high concentration of the substrate while GPx acts at lower concentrations. They also suggested that H2O2 concentration may be lower than in other chronic inflammatory diseases, with oxidative damage being mediated possibly by Ho [51].

Glutathione reductase (GR), an oxidative stress inducible enzyme, plays a significant role in the peroxyl scavenging mechanism and in maintaining functional integration of the cell membranes.

Glutathione reductase is a flavoenzyme dependent on NADPH that catalyzes the reduction of GSSH to GSH. Feijoo et al. [52] observed that myeloperoxidase levels are elevated in patients with chronic inflammatory disease, especially those with active disease, and that high myeloperoxidase levels are related to an increase in oxidative damage and the inflammatory response, for myeloperoxidase and GR seem to show a similar activity pattern based on the availability of NADPH. Erythrocyte GSH and glutathione reductase levels rise in healthy individuals exposed to chronic oxidative stress [53]. These findings suggest that GSH levels may be inappropriate in patients with active rheumatoid arthritis, perhaps reflecting impaired glutathione reductase activity as observed in our study. The study by Aryaein et al. [54] showed that GR, vitamin E, Beta-carotene was lower and MDA was higher in the patient group than in controls. Kamanli et al. [22] observed significantly lower GSH-Px, catalase, levels of GSH in plasma of RA patients. However higher GR activity have also been reported in RA [55]. Kerimova et al. [56] also reported decreased catalase and unaffected GR activities in RA subjects. Low GR activities in the red blood cells and polymorphonuclear leucocytes of patients with RA was reported by Mulherin et al. [57]. Vanella et al. [58] described reduced EGR activity in 15 patients with rheumatoid arthritis and Tarp et al. recorded a similar finding in nine patients with rheumatoid arthritis [59].

In our patients alkaline phosphatase (ALP) activity is higher relative to control. ALP showed strong positive and significant relationship with SOD. ALPs role is implicated in osteoid formation and mineralization and expression of its isoform is in osteoblasts, leucocytes, liver, kidney, breast and brain [60,61]. The bone formation markers are measured in serum and about half of ALP in serum comes from bone. Several studies [62-64] have reported high serum ALP levels in RA patients. The increased activity may be due to inflammatory cytokines as interleukin-1 (IL-1) which has been correlated with the acute phase reactants [62] and CRP levels. The role of T-cells is well documented in the pathogenesis of RA. Raised ALP may be due to its leakage from injured or killed cells.

Alkaline phosphatase has been implicated as marker in RA patients. It can provide diagnostic information by determination of isoform of ALP derived from liver or bone [65]. Thus MDA and antioxidants systems work reciprocally to keep oxidative stress mediated damage in control. An inverse association between serum antioxidant levels and inflammation have been reported [66].

Study by Jalili et al. [67] showed that antioxidants may significantly improve disease activity but do not affect the number of painful and swollen joints. Thus antioxidants may be helpful in control of clinical outcomes and oxidative stress in RA patients. In conclusion oxidative stress management may be considered a therapeutic option for RA along with DMARD. Supplementation of antioxidants along with catalase and/or GPX may confer more protection.


The work was supported by grant of Department of Biotechnology, Ministry of Science and Technology, Govt. of India (BT/ PR10980/GBD/27/134/2008). Fellowship grant to Vivek Kumar by Indian Council of Medical Research (3/1/3/JRF-2009/MPD-66(34495)) is duly acknowledged.


The authors have no conflict of interest.


  1. Bodman KB, Roitt IM (1994) The pathophysiology of rheumatoid arthritis. Fund Am ClinImmunol 2: 73.
  2. Feldmann M, Brennan FM, Maini RN (1996) Role of cytokines in rheumatoid arthritis.Annu Rev Immunol 14: 397-440.
  3. Jaswal S, Mehta HC, Sood AK, Kaur J (2003) Antioxidant status in rheumatoid arthritis and role of antioxidant therapy.ClinChimActa 338: 123-129.
  4. Mahajan A, Tandon VR (2004) Antioxidants and rheumatoid arthritis. J Indian RheumatolAssoc 12: 139–142.
  5. Demirbag R, Yilmaz R, Erel O, Gultekin U, Asci D, et al. (2005) The relationship between potency of oxidative stress and severity of dilated cardiomyopathy.Can J Cardiol 21: 851-855.
  6. Ozgocmen S, Ozyurt H, Sogut S, Akyol O (2006) Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stress and nitric oxide.RheumatolInt 26: 585-597.
  7. Henrotin Y, Kurz B, Aigner T (2005) Oxygen and reactive oxygen species in cartilage degradation: friends or foes?Osteoarthritis Cartilage 13: 643-654.
  8. Marshall WJ, Bangert SK (1995) Clinical Biochemistry – Metabolic and clinical aspects. Free radicals.
  9. Vasudevan DM, Sreekumari S (2001) Textbook of Biochemistry for Medical students. 3rd edtn. Jaypee Digital Publishers, India.
  10. Nurcomb HL, Bucknall RC, Edward SW (1991) Activation of neutrophil myeloperoxidase – hydrogen peroxide system in synovial fluid isolated from patients with rheumatoid arthritis. Ann Rheum Dis 50: 237-242.
  11. Blake DR, Hall ND, Treby DA, Halliwell B, Gutteridge JM (1981) Protection against superoxide and hydrogen peroxide in synovial fluid from rheumatoid patients.ClinSci (Lond) 61: 483-486.
  12. Heliövaara M, Knekt P, Aho K, Aaran RK, Alfthan G, et al. (1994) Serum antioxidants and risk of rheumatoid arthritis.Ann Rheum Dis 53: 51-53.
  13. Mazzetti I, Grigolo B, Borzì RM, Meliconi R, Facchini A (1996) Serum copper/zinc superoxide dismutase levels in patients with rheumatoid arthritis.Int J Clin Lab Res 26: 245-249.
  14. Shah ZA, Vohora SB (2002) Antioxidant/restorative effects of calcined gold preparations used in indian systems ofmedicine against global and focal models of ischaemia. PharmacolToxicol 90: 254–259.
  15. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, et al. (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31: 315–324.
  16. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction.Anal Biochem 95: 351-358.
  17. Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase.J BiolChem 247: 3170-3175.
  18. Sinha AK (1972) Colorimetric assay of catalase.Anal Biochem 47: 389-394.
  19. Bergmayer HU (1963) Method of enzymatic analysis. Wiley, New York, USA.
  20. Gutteridge JM (1995) Lipid peroxidation and antioxidants as biomarkers of tissue damage.ClinChem 41: 1819-1828.
  21. Ali AM, Habeeb RA, El-Azizi NO, Khattab DA, Abo-Shady RA, et al. (2014) Higher nitric oxide levels are associated with disease activity in Egyptian rheumatoid arthritis patients. Rev Bras Reumatol 54: 446-451.
  22. Kamanli A, Naziroqlu M, Aydilek N, Hacievliyagil C (2004) Plasma lipid peroxidation and antioxidant levels in patients with rheumatoid arthritis.Cell BiochemFunct 22: 53-57.
  23. Sarban S, Kocyigit A, Yazar M, Isikan UE (2005) Plasma total antioxidant capacity, lipid peroxidation, and erythrocyte antioxidant enzyme activities in patients with rheumatoid arthritis and osteoarthritis. ClinBiochem 38: 981-986.
  24. Hassan MQ, Hadi RA, Al-Rawi ZS, Padron VA, Stohs SJ (2001) The glutathione defense system in the pathogenesis of rheumatoid arthritis.J ApplToxicol 21: 69-73.
  25. Afonso V, Champy R, Mitrovic D, Collin P, Lomri A (2007) Reactive oxygen species and superoxide dismutases: role in joint diseases.Joint Bone Spine 74: 324-329.
  26. Mirshafiey A, Mohsenzadegan M (2008) The role of reactive oxygen species in immunopathogenesis of rheumatoid arthritis.Iran J Allergy Asthma Immunol 7: 195-202.
  27. McCord JM (2000) The evolution of free radicals and oxidative stress.Am J Med 108: 652-659.
  28. Gambhir JK, Lali P, Jain AK (1997) Correlation between blood antioxidant levels and lipid peroxidation in rheumatoid arthritis.ClinBiochem 30: 351-355.
  29. Mishra R, Singh A, Chandra V, Negi MP, Tripathy BC, et al. (2012) A comparative analysis of serological parameters and oxidative stress in osteoarthritis and rheumatoid arthritis.RheumatolInt 32: 2377-2382.
  30. Patel SL, Kumar V, Mishra R, Vishal C, Mahendra N, et al. (2015) Effectiveness of methotrexate therapy with occasional corticosteroid in rheumatoid arthritis. Current orthopaedic Practice 26: 148-154.
  31. Pallinti V, Ganesan N, Anbazhagan M, Rajasekhar G (2009) Serum biochemical markers in rheumatoid arthritis.Indian J BiochemBiophys 46: 342-344.
  32. Thiele GM, Duryee MJ, Anderson DR, Klassen LW, Mohring SM, et al. (2015) Malondialdehyde-acetaldehyde adducts and anti-malondialdehyde-acetaldehyde antibodies in rheumatoid arthritis. Arthritis Rheumatol 67: 645-655.
  33. Armagan A, Uzar E, Uz E, Yilmaz HR, Kutluhan S, et al. (2008) Caffeic acid phenethyl ester modulates methotrexate-induced oxidative stress in testes of rat. Hum ExpToxicol 27: 547–552.
  34. Al-Saleh E, Al-Harmi J, Nandakumaran M, Al-Shammari M, Al-Jassar W (2009) Effect of methotrexate administration on status of some essential trace elements and antioxidant enzymes in pregnant rats in late gestation. GynecolEndocrinol 25: 816–822
  35. Vijayakumar D, Suresh K, Manoharan S (2006) Lipid peroxidation and antioxidant status in blood of rheumatoid arthritis patients.Indian J ClinBiochem 21: 105.
  36. Cimen MY, Cimen OB, Kacmaz M, Ozturk HS, Yorgancioglu R, et al. (2000) Oxidant/antioxidant status of the erythrocytes from patients with rheumatoid arthritis.ClinRheumatol 19: 275-277.
  37. Gregory EM, Fridovich I (1973) Induction of superoxide dismutase by molecular oxygen.J Bacteriol 114: 543-548.
  38. Hassan HM, Fridovich I (1977) Regulation of the synthesis of superoxide dismutase in Escherichia coli. Induction by methyl viologen.J BiolChem 252: 7667-7672.
  39. Nourmohammadi I, Athari-Nikazm S, Vafa MR, Bidari A, Jazayeri S, et al. (2010) Effect of antioxidant supplementations on oxidative stress in rheumatoid arthritis patients. J BiolScien 10: 63-66.
  40. Al-Youzbaki WB, Fatehi HIA, Yassen AT (2013) Oxidant and Antioxidant Status in Patients with Rheumatoid Arthritis Treated by Methotrexate. Iraqi J Comm Med.
  41. Sung JY, Hong JH, Kang HS, Choi I, Lim SD, et al. (2000) Methotrexate suppresses the interleukin-6 induced generation of reactive oxygen species in the synoviocytes of rheumatoid arthritis.Immunopharmacology 47: 35-44.
  42. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases.Nature 443: 787-795.
  43. Zaghloul N, Patel H, Codipilly C, Marambaud P, Dewey S, et al. (2014) Overexpression of Extracellular Superoxide Dismutase Protects against Brain Injury Induced by Chronic Hypoxia. PLoS One 9: e108168.
  44. Mohamad A, Khaleka MAA, Elsalawya AM, Hazaab SM (2011) Assessment of lipid peroxidation and antioxidant status in rheumatoid arthritis and osteoarthritis patients. Egyptian Rheumatologist 33: 179-185.
  45. Igari T, Kaneda H, Horiuchi S, Ono S (1982) A remarkable increase of superoxide dismutase activity in synovial fluid of patients with rheumatoid arthritis. ClinOrthopRelat Res pp: 282-287.
  46. Mateen S, Moin S, Khan AQ, Zafar A, Fatima N (2016) Increased Reactive Oxygen Species Formation and Oxidative Stress in Rheumatoid Arthritis.PLoS One 11: e0152925.
  47. Taysi S, Polat F, Gul M, Sari RA, Bakan E (2002) Lipid peroxidation, some extracellular antioxidants, and antioxidant enzymes in serum of patients with rheumatoid arthritis.RheumatolInt 21: 200-204.
  48. Veselinovic M, Barudzic N, Vuletic M, Zivkovic V, Tomic-Lucic A, et al. (2014) Oxidative stress in rheumatoid arthritis patients: relationship to diseases activity. Mol Cell Biochem 391: 225–232.
  49. Benhamou PY, Moriscot C, Richard MJ, Beatrix O, Badet L, et al. (1998) Adenovirus-mediated catalase gene transfer reduces oxidant stress in human, porcine and rat pancreatic islets. Diabetologia 41: 1093-1100.
  50. García-González A, Gaxiola-Robles R, Zenteno-Savín T (2015) Oxidative stress in patients with rheumatoid arthritis.Rev Invest Clin 67: 46-53.
  51. Prego EC, Balboa JP, Miranda EC (1997) Enzymes involved as physiological barriers to scavenge free radicals: III. glutathione peroxidase. Rev Cubana Invest Biomed 16: 10-15.
  52. Feijóo M, Túnez I, Ruiz A, Tasset I, Muñoz E, et al. (2010) [Oxidative stress biomarkers as indicator of chronic inflammatory joint diseases stage].ReumatolClin 6: 91-94.
  53. Evelo CTA, Palmen NGM, Artur Y, Janssen GME (1992) Changes in blood glutathione concentrations, and in erythrocyte glutathione reductase and glutathione S-transferase activity after running training and after participation in contests. Eur J ApplPhysiolOccupPhysiol 64: 354-358.
  54. Aryaeian N, Djalali N, Shahram F, Jazayeri SH, Chamari M, et al. (2011) Beta-Carotene, Vitamin E, MDA, Glutathione Reductase and Arylesterase Activity Levels in Patients with Active Rheumatoid Arthritis. Iranian J Publ Health 40: 102-109.
  55. Bazzichi L, Ciompi ML, Betti L, Rossi A, Melchiorre D, et al. (2002) Impaired glutathione reductase activity and levels of collagenase and elastase in synovial fluid in rheumatoid arthritis.ClinExpRheumatol 20: 761-766.
  56. Kerimova AA, Atalay M, Yusifov EY, Kuprin SP, Kerimov TM (2000) Antioxidant enzymes; possible mechanism of gold compound treatment in rheumatoid arthritis.Pathophysiology 7: 209-213.
  57. Mulherin DM, Thurnham DI, Situnayake RD (1996) Glutathione reductase activity, riboflavin status, and disease activity in rheumatoid arthritis.Ann Rheum Dis 55: 837-840.
  58. Vanella A, Raqusa N, Campisi A, Sorrenti V, Murabito L, et al. (1987) Antioxidant enzymatic systems in erythrocytes from patients with rheumatoid arthritis. Med Sci Res 15: 1187-1188.
  59. Tarp U, Stengaard-Pedersen K, Hansen JC, Thorling EB (1992) Glutathione redox cycle enzymes and selenium in severe rheumatoid arthritis: lack of antioxidative response toselenium supplementation in polymorphonuclear leucocytes. Ann Rheum Dis 51: 1044-1049.
  60. Weiss MJ, Henthorn PS, Lafferty MA, Slaughter C, Raducha M, et al. (1986) Isolation and characterization of a cDNA encoding a human liver/bone/kidney-type alkaline phosphatase.ProcNatlAcadSci U S A 83: 7182-7186.
  61. Gum JR, Hicks JW, Sack TL, Kim YS (1990) Molecular cloning of complementary DNAs encoding alkaline phosphatase in human colon cancer cells.Cancer Res 50: 1085-1091.
  62. Thompson PW, Houghton BJ, Clifford C, Jones DD, Whitaker KB, et al. (1990) The source and significance of raised serum enzymes in rheumatoid arthritis.Q J Med 76: 869-879.
  63. Nanke Y, Kotake S, Akama H, Kamatani N (2002) Alkaline phosphatase in rheumatoid arthritis patients: possible contribution of bone-type ALP to the raised activities of ALP in rheumatoid arthritis patients. ClinRheumatol21: 198-202.
  64. Spooner RJ, Smith DH, Bedford D, Beck PR (1982) Serum gamma-glutamyltransferase and alkaline phosphatase in rheumatoid arthritis.J ClinPathol 35: 638-641.
  65. Vaithialingam A, Lakshmi TM, Suryaprakash G, Edukondalu AD, Reddy EP (2013) Alkaline phosphatase levels in Rheumatoid arthritis and Osteoporosis in clinical practice. Journal of current trends in clinical Medicine and laboratory biochemistry 1: 20-23.
  66. Paredes S, Girona J, Hurt-Camejo E, Vallvé JC, Olivé S, et al. (2002) Antioxidant vitamins and lipid peroxidation in patients with rheumatoid arthritis: association with inflammatory markers.J Rheumatol 29: 2271-2277.
  67. Jalili M, Kolahi S, Aref-Hosseini SR, Mamegani ME, Hekmatdoost A (2014) Beneficial role of antioxidants on clinical outcomes and erythrocyte antioxidant parameters in rheumatoid arthritis patients.Int J Prev Med 5: 835-840.
Citation: Kumar V, Prakash J, Gupta V, Khan MY (2016) Antioxidant Enzymes in Rheumatoid Arthritis. J Arthritis 5:206.

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