{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T05:09:39Z","timestamp":1767676179335},"reference-count":50,"publisher":"American Diabetes Association","issue":"10","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,10,1]]},"abstract":"<jats:p>Reactive oxygen species, such as superoxide, and nitrogen oxides, such as peroxynitrite, are thought to contribute to \u03b2-cell destruction during the disease process that leads to type 1 diabetes. EUK-8 is a member of a new class of synthetic salen-manganese compounds with low toxicity that possess catalytic superoxide dismutase, peroxidase, and catalase activity that can inactivate superoxide and nitrogen oxides (e.g., peroxynitrite and nitrogen dioxide). We observed that EUK-8 administration inhibited the adoptive transfer of type 1 diabetes to NOD mice. In addition, administration of EUK-8 to NOD mice with established autoimmunity completely prevented the development of type 1 diabetes for up to 1 year in age, even though the treatment was discontinued after 35 weeks of age. EUK-8 treatment also prolonged the survival of islet allografts in newly diabetic NOD mice. Thus, reactive oxygen and nitrogen species contribute to the pathoetiology of both spontaneous type 1 diabetes and allograft rejection. In cultures of NIT-1 cells, EUK-8 inhibited cytotoxicity caused by superoxide as well as nitric oxide. Collectively, our findings implicate a greater role for nitrogen oxides (other than peroxynitrite) in \u03b2-cell damage. Antioxidants designed to prevent the formation of both cytotoxic reactive oxygen and nitrogen species may effectively protect \u03b2-cells from spontaneous autoimmunity and alloresponses.<\/jats:p>","DOI":"10.2337\/diabetes.53.10.2574","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"2574-2580","update-policy":"http:\/\/dx.doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":18,"title":["A Salen-Manganese Catalytic Free Radical Scavenger Inhibits Type 1 Diabetes and Islet Allograft Rejection"],"prefix":"10.2337","volume":"53","author":[{"given":"Angelica P.","family":"Olcott","sequence":"first","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georges","family":"Tocco","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jide","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Zekzer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon","family":"Fukuto","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Ignarro","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel L.","family":"Kaufman","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031207301855200_R1","unstructured":"Rabinovitch A: Free radicals as mediators of pancreatic islet beta-cell injury in autoimmune diabetes. 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