Luminescence experiments involved in the mechanism of streptozotocin diabetes and cataract formation
- 23 July 2008
- journal article
- research article
- Published by Wiley in Luminescence
- Vol. 23 (6), 386-391
- https://doi.org/10.1002/bio.1050
Abstract
Streptozotocin (STZ)-induced diabetes is linked to excessive nitric oxide (NO), and possibly peroxynitrite (OONO–) and/or other nitrogen oxides, e.g. nitrogen trioxide (N2O3), which damages DNA of pancreatic β cells, causing death and loss of insulin. Simultaneous injection of carboxy-PTIO (CPTIO) and STZ prevents diabetes and cataract formation in rats, whereas 4-hydroxy-Tempo (4HT) does not. CPTIO oxidizes nitric oxide to nitrite, which prevents production of the diabetogenic toxin. Peroxynitrite may not be involved, since 4HT (converts O2– to H2O2) injected with STZ produces diabetes. All six of the control rats injected with STZ became diabetic and developed cataracts after 3 months. Eight rats injected with STZ and CPTIO were non-diabetic with no cataracts up to a year. This work establishes the idea that excessive nitric oxide is a primary initiator in STZ diabetes. Luminescence experiments using OONO– generation from SIN-1 with L-012 indicates that 4HT is an effective inhibitor, while CPTIO is ineffective. Experiments with dilute solutions of nitrogen trioxide added to ladder or plasmid DNA reveal extensive nicking of DNA, thereby raising the possibility that other oxides of nitrogen could be involved with the damage to DNA. It can be concluded that diabetes can be prevented by oxidizing excessive NO from STZ. Copyright © 2008 John Wiley & Sons, Ltd.Keywords
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