Effect of methotrexate on blood purine and pyrimidine levels in patients with rheumatoid arthritis

Smoleńska, Żaneta; Kaznowska, Z; Zarowny, Donald P.; Simmonds, H. Anne; Smolenski, R.T.

doi:10.1093/rheumatology/38.10.997

Cited by 56 publications

(42 citation statements)

References 20 publications

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“…Moreover, it has been also reported that uric acid has not been a strong antioxidant and might not protect against free radicals (Smolenska et al 1999). In the present study, there was no significant difference between the BD and the control groups in the levels of albumin, bilirubin and uric acid.…”

Section: Discussioncontrasting

confidence: 58%

Decreased Total Antioxidant Response and Increased Oxidative Stress in Behcet's Disease

Işık

Koca

Üstündağ

et al. 2007

Tohoku J. Exp. Med.

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Behcet's disease (BD) is a chronic systemic inflammatory disease. Inflammatory reactions trigger the oxidative stress and oxidants decrease the level of antioxidants. In the present study, we aimed to determine serum oxidative/antioxidative status in patients with BD. Serum antioxidative status was evaluated by measuring total antioxidant capacity (TAC), paraoxonase 1, arylesterase, sulfhydryl groups and ceruloplasmin in patients with BD and in healthy controls. Serum oxidative status was evaluated by measuring total peroxide (TP), lipid hydroperoxides and oxidative stress index (OSI). OSI was calculated by percent ratio of TP to TAC. Serum levels of TAC, sulfhydryl groups and activities of paraoxonase 1, arylesterase, and ceruloplasmin were significantly lower in patients than in controls ( p < 0.001 for all). In contrast, TP, lipid hydroperoxides and OSI values were significantly higher in patients than in controls ( p < 0.001 for all). Further, the level of TAC was negatively correlated with the levels of TP, lipid hydroperoxides and OSI both in the BD (r = −0.578, p < 0.01; r = −0.559, p < 0.01 and r = −0.552, p < 0.01, respectively) and the control groups (r = −0.469, p < 0.05; r = −0.351, p < 0.05 and r = −0.391, p < 0.05, respectively). These results indicate that the oxidant parameters increased and antioxidant parameters decreased in patients with BD; therefore, these patients might have been exposed to oxidative stress. We suggest that impaired oxidant/ antioxidant balance should be taken into consideration in the follow-up of patients with BD.

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Section: Discussioncontrasting

confidence: 58%

Decreased Total Antioxidant Response and Increased Oxidative Stress in Behcet's Disease

Işık

Koca

Üstündağ

et al. 2007

Tohoku J. Exp. Med.

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“…In the work by Smolenska et al (1999), a single dose of methotrexate significantly reduced purine synthesis for a day without any concomitant increase in erythrocyte AICAR concentration. The observation that purine synthesis is inhibited for a day after a dose of methotrexate is consistent with and probably accounts for the methotrexate-mediated reduction in antigen-induced proliferation of T cells, although the clinical importance of reduced cellular proliferation 1 day a week is unknown.…”

Section: Methotrexate Increases Extracellular Adenosine Concentratmentioning

confidence: 97%

“…Other evidence against the hypothesis that methotrexate promotes adenosine release and adenosine mediates the anti-inflammatory effects were provided by two recent clinical studies (Egan et al, 1999;Smolenska et al, 1999). In the work by Smolenska et al (1999), a single dose of methotrexate significantly reduced purine synthesis for a day without any concomitant increase in erythrocyte AICAR concentration.…”

Section: Methotrexate Increases Extracellular Adenosine Concentratmentioning

confidence: 99%

Low-Dose Methotrexate: A Mainstay in the Treatment of Rheumatoid Arthritis

Cronstein¹

2005

Pharmacol Rev

466

311

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“…33 In patients with RA, MTX is thought to act through inhibition of T cell proliferation. 35 We therefore hypothesized that genetic susceptibility markers may also be important predictors of MTX outcome. We report that the RA susceptibility allele of the SNP marker rs6920220 (OLIG3/TNFAIP3) was associated with being less likely to maintain MTX monotherapy by year 1 and year 2, in both IP and RA (Table 2).…”

Section: Discussionmentioning

confidence: 99%

A genetic marker at the OLIG3/TNFAIP3 locus associates with methotrexate continuation in early inflammatory polyarthritis: results from the Norfolk Arthritis Register

et al. 2010

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Whole-genome association studies in rheumatoid arthritis have identified single-nucleotide polymorphisms (SNPs) predisposing to disease with moderate risk. We aimed to investigate the role of these markers in predicting methotrexate (MTX) response, measured by continuation on MTX monotherapy in patients with recent onset inflammatory polyarthritis (IP). In all, 19 SNPs were genotyped in 736 patients treated with MTX following registration, or not more than 3 months before registration, to the Norfolk Arthritis Register. The association of SNPs with MTX continuation by year 1 and by year 2 was investigated using Cox proportional hazard regression models. A SNP within the OLIG3/TNFAIP3 locus (rs6920220) was associated with being less likely to maintain MTX monotherapy at year 1, hazards ratio (HR) 1.73 (1.18, 2.52) and year 2, HR 1.49 (1.11, 2.00); correlating with an increased in adverse events. Weak evidence for an effect at the PTPN22 locus was also observed. These findings require replication in other large datasets.

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Effect of methotrexate on blood purine and pyrimidine levels in patients with rheumatoid arthritis

Cited by 56 publications

References 20 publications

Decreased Total Antioxidant Response and Increased Oxidative Stress in Behcet's Disease

Decreased Total Antioxidant Response and Increased Oxidative Stress in Behcet's Disease

Low-Dose Methotrexate: A Mainstay in the Treatment of Rheumatoid Arthritis

A genetic marker at the OLIG3/TNFAIP3 locus associates with methotrexate continuation in early inflammatory polyarthritis: results from the Norfolk Arthritis Register

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