{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:34:40Z","timestamp":1786977280812,"version":"build-2736575974"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,27]],"date-time":"2020-01-27T00:00:00Z","timestamp":1580083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["ZIAAR041199"],"award-info":[{"award-number":["ZIAAR041199"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007820","name":"Alliance for Lupus Research","doi-asserted-by":"publisher","award":["TIL"],"award-info":[{"award-number":["TIL"]}],"id":[{"id":"10.13039\/100007820","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>A role for mitochondrial dysfunction has been proposed in the immune dysregulation and organ damage characteristic of systemic lupus erythematosus (SLE). Idebenone is a coenzyme Q10 synthetic quinone analog and an antioxidant that has been used in humans to treat diverse diseases in which mitochondrial function is impaired. This study was undertaken to assess whether idebenone ameliorates lupus in murine models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Idebenone was administered orally to MRL\/\n                      <jats:italic>lpr<\/jats:italic>\n                      mice at 2 different doses (1 gm\/kg or 1.5 gm\/kg idebenone\u2010containing diet) for 8 weeks. At peak disease activity, clinical, immunologic, and metabolic parameters were analyzed and compared to those in untreated mice (n = 10 per treatment group). Results were confirmed in the lupus\u2010prone NZM2328 mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In MRL\/\n                      <jats:italic>lpr<\/jats:italic>\n                      mice, idebenone\u2010treated mice showed a significant reduction in mortality incidence (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.01 versus untreated mice), and the treatment attenuated several disease features, including glomerular inflammation and fibrosis (each\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05 versus untreated mice), and improved renal function in association with decreased renal expression of interleukin\u201017A (IL\u201017A) and mature IL\u201018. Levels of splenic proinflammatory cytokines and inflammasome\u2010related genes were significantly decreased (at least\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05 and some with higher significance) in mice treated with idebenone, while no obvious drug toxicity was observed. Idebenone\u00a0inhibited neutrophil extracellular trap formation in neutrophils from lupus\u2010prone mice (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05) and human patients with SLE. Idebenone also improved mitochondrial metabolism (30% increase in basal respiration and ATP production), reduced the extent of heart lipid peroxidation (by one\u2010half that of untreated mice), and significantly improved endothelium\u2010dependent vasorelaxation (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001). NZM2328 mice exposed to idebenone also displayed improvements in renal and systemic inflammation, reducing the kidney pathology score (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05), IgG\/C3 deposition (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05), and the gene expression of interferon, proinflammatory, and inflammasome\u2010related genes (at least\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.05 and some with higher significance).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Idebenone ameliorates murine lupus disease activity and the severity of organ damage, supporting the hypothesis that agents that modulate mitochondrial biologic processes may have a therapeutic role in human SLE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.41128","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:55:51Z","timestamp":1569891351000},"page":"454-464","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Improved Mitochondrial Metabolism and Reduced Inflammation Following Attenuation of Murine Lupus With Coenzyme Q10 Analog Idebenone"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8468-6518","authenticated-orcid":false,"given":"Luz P.","family":"Blanco","sequence":"first","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hege L.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghao","family":"Wang","sequence":"additional","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u00edma L.","family":"Lightfoot","sequence":"additional","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nickie","family":"Seto","sequence":"additional","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Carmona\u2010Rivera","sequence":"additional","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu\u2010Xi","family":"Yu","sequence":"additional","affiliation":[{"name":"National Heart, Lung, and Blood Institute NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"NIH  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S. 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