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- Title
A salen-manganese catalytic free radical scavenger inhibits type 1 diabetes and islet allograft rejection.
- Authors
Olcott, Angelica P.; Tocco, Georges; Tian, Jide; Zekzer, Dan; Fukuto, Jon; Ignarro, Louis; Kaufman, Daniel L.
- Abstract
Reactive oxygen species, such as superoxide, and nitrogen oxides, such as peroxynitrite, are thought to contribute to beta-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 beta-cell damage. Antioxidants designed to prevent the formation of both cytotoxic reactive oxygen and nitrogen species may effectively protect beta-cells from spontaneous autoimmunity and alloresponses.
- Subjects
REACTIVE oxygen species; NITROGEN oxides; NITROGEN; DIABETES; LABORATORY mice
- Publication
Diabetes, 2004, Vol 53, Issue 10, p2574
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.53.10.2574