A salen-manganese catalytic free radical scavenger inhibits type 1 diabetes and islet allograft rejection
| Autor: | Jide Tian, Louis J. Ignarro, Angelica P. Olcott, Daniel L. Kaufman, Dan Zekzer, Georges Tocco, Jon M. Fukuto |
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| Rok vydání: | 2004 |
| Předmět: |
Graft Rejection
medicine.medical_specialty Endocrinology Diabetes and Metabolism Islets of Langerhans Transplantation Catalysis Nitric oxide Superoxide dismutase chemistry.chemical_compound Mice Mice Inbred NOD Internal medicine Internal Medicine medicine Organometallic Compounds Animals NOD mice chemistry.chemical_classification Reactive oxygen species Mice Inbred BALB C biology Superoxide Free Radical Scavengers Free radical scavenger Ethylenediamines Endocrinology Diabetes Mellitus Type 1 chemistry Manganese Compounds Catalase biology.protein Female Peroxynitrite |
| Zdroj: | Diabetes. 53(10) |
| ISSN: | 0012-1797 |
| Popis: | Reactive oxygen species, such as superoxide, and nitrogen oxides, such as peroxynitrite, are thought to contribute to β-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 β-cell damage. Antioxidants designed to prevent the formation of both cytotoxic reactive oxygen and nitrogen species may effectively protect β-cells from spontaneous autoimmunity and alloresponses. |
| Databáze: | OpenAIRE |
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