PMID- 29644482 OWN - NLM STAT- MEDLINE DCOM- 20181030 LR - 20181202 IS - 1591-9528 (Electronic) IS - 1591-8890 (Linking) VI - 18 IP - 3 DP - 2018 Aug TI - Metabolic syndrome and the decreased levels of uric acid by leflunomide favor redox imbalance in patients with rheumatoid arthritis. PG - 363-372 LID - 10.1007/s10238-018-0500-y [doi] AB - Oxidative stress plays a role in the pathophysiology of rheumatoid arthritis (RA). The aim of the present study was to verify the influence of metabolic syndrome (MetS) and disease-modifying antirheumatic drugs on nitrosative and oxidative biomarkers in patients with RA. A total of 177 patients with RA and 150 healthy volunteers participated in this study, which measured lipid hydroperoxides, advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), carbonyl protein, total radical-trapping antioxidant parameter (TRAP), uric acid (UA), and C-reactive protein (CRP). NOx and the NOx/TRAP ratio were significantly increased in RA, while no significant differences in lipid hydroperoxides, AOPP, UA, and TRAP levels were found between both groups. Treatment with leflunomide was associated with increased levels of carbonyl protein, and lowered levels in TRAP and UA, while the NOx/TRAP ratio further increased. NOx and the NOx/TRAP ratio were significantly higher in women than in men, while TRAP and UA were significantly lower in women. MetS was accompanied by increased AOPP and UA levels. RA was best predicted by increased NOx/TRAP ratio, CRP, and BMI. In conclusion, our data demonstrated that NOx and NOx/TRAP are strongly associated with RA physiopathology. Our findings suggest that inhibition of iNOS may become an interesting therapeutic approach for the treatment of RA. In addition, the presence of MetS and a decrease in levels of UA by leflunomide favor redox imbalance in RA patients. More studies are needed to evaluate the impact of antioxidant capacity reduction on RA progression. FAU - Costa, Neide Tomimura AU - Costa NT AD - Laboratory of Research in Applied Immunology, University of Londrina, Londrina, Parana, Brazil. AD - Department of Internal Medicine, University of Londrina, Londrina, Parana, Brazil. FAU - Scavuzzi, Bruna Miglioranza AU - Scavuzzi BM AD - Laboratory of Research in Applied Immunology, University of Londrina, Londrina, Parana, Brazil. FAU - Iriyoda, Tatiana Mayumi Veiga AU - Iriyoda TMV AD - Department of Rheumatology - PUC, Pontificia Universidade Catolica, Londrina, Parana, Brazil. FAU - Lozovoy, Marcell Alysson Batisti AU - Lozovoy MAB AD - Department of Clinical Pathology, Clinical Analysis and Toxicology - University of Londrina, Robert Koch Avenue No. 60 Bairro Cervejaria, Londrina, Parana, CEP: 86038-440, Brazil. FAU - Alfieri, Daniela Frizon AU - Alfieri DF AD - Laboratory of Research in Applied Immunology, University of Londrina, Londrina, Parana, Brazil. FAU - de Medeiros, Fabiano Aparecido AU - de Medeiros FA AD - Post Graduate Program in Clinical and Laboratory Pathophysiology, University of Londrina, Londrina, Parana, Brazil. FAU - de Sa, Marcelo Candido AU - de Sa MC AD - Post Graduate Program in Clinical and Laboratory Pathophysiology, University of Londrina, Londrina, Parana, Brazil. FAU - Micheletti, Pamela Lonardoni AU - Micheletti PL AD - Post Graduate Program in Clinical and Laboratory Pathophysiology, University of Londrina, Londrina, Parana, Brazil. FAU - Sekiguchi, Bruno Alexandre AU - Sekiguchi BA AD - Laboratory of Research in Applied Immunology, University of Londrina, Londrina, Parana, Brazil. FAU - Reiche, Edna Maria Vissoci AU - Reiche EMV AD - Department of Clinical Pathology, Clinical Analysis and Toxicology - University of Londrina, Robert Koch Avenue No. 60 Bairro Cervejaria, Londrina, Parana, CEP: 86038-440, Brazil. FAU - Maes, Michael AU - Maes M AD - IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, VIC, Australia. FAU - Simao, Andrea Name Colado AU - Simao ANC AUID- ORCID: 0000-0002-2073-6782 AD - Department of Clinical Pathology, Clinical Analysis and Toxicology - University of Londrina, Robert Koch Avenue No. 60 Bairro Cervejaria, Londrina, Parana, CEP: 86038-440, Brazil. deianame@yahoo.com.br. FAU - Dichi, Isaias AU - Dichi I AD - Department of Internal Medicine, University of Londrina, Londrina, Parana, Brazil. LA - eng PT - Journal Article DEP - 20180411 PL - Italy TA - Clin Exp Med JT - Clinical and experimental medicine JID - 100973405 RN - 0 (Advanced Oxidation Protein Products) RN - 0 (Antirheumatic Agents) RN - 0 (Isoxazoles) RN - 0 (Lipid Peroxides) RN - 268B43MJ25 (Uric Acid) RN - 31C4KY9ESH (Nitric Oxide) RN - 9007-41-4 (C-Reactive Protein) RN - EC 1.14.13.39 (NOS2 protein, human) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - G162GK9U4W (Leflunomide) SB - IM MH - Adolescent MH - Adult MH - Advanced Oxidation Protein Products/blood/genetics MH - Aged MH - Antirheumatic Agents/*therapeutic use MH - Arthritis, Rheumatoid/blood/complications/*drug therapy/pathology MH - C-Reactive Protein/metabolism MH - Case-Control Studies MH - Disease Progression MH - Female MH - Gene Expression MH - Humans MH - Isoxazoles/*therapeutic use MH - Leflunomide MH - Lipid Peroxides/blood MH - Male MH - Metabolic Syndrome/blood/complications/*drug therapy/pathology MH - Middle Aged MH - Nitric Oxide/blood MH - Nitric Oxide Synthase Type II/blood/genetics MH - Oxidation-Reduction MH - Oxidative Stress/drug effects MH - Protein Carbonylation MH - Sex Factors MH - Uric Acid/antagonists & inhibitors/*blood OTO - NOTNLM OT - Leflunomide OT - Metabolic syndrome OT - Nitrosative stress OT - Oxidative stress OT - Rheumatoid arthritis EDAT- 2018/04/13 06:00 MHDA- 2018/10/31 06:00 CRDT- 2018/04/13 06:00 PHST- 2018/01/18 00:00 [received] PHST- 2018/04/03 00:00 [accepted] PHST- 2018/04/13 06:00 [pubmed] PHST- 2018/10/31 06:00 [medline] PHST- 2018/04/13 06:00 [entrez] AID - 10.1007/s10238-018-0500-y [pii] AID - 10.1007/s10238-018-0500-y [doi] PST - ppublish SO - Clin Exp Med. 2018 Aug;18(3):363-372. doi: 10.1007/s10238-018-0500-y. Epub 2018 Apr 11.