Generation of hydroxyl radicals mediated by streptozotocin in pancreatic islets of mice in vitro

被引:35
作者
Gille, L
Schott-Ohly, P
Friesen, N
Waide, SSI
Udilova, N
Nohl, H
Gleichmann, H
机构
[1] Univ Dusseldorf, German Diabet Res Inst, Germad Diabet Ctr, D-40225 Dusseldorf, Germany
[2] Vet Univ Vienna, Inst Pharmacol & Toxicol, A-1030 Vienna, Austria
来源
PHARMACOLOGY & TOXICOLOGY | 2002年 / 90卷 / 06期
关键词
D O I
10.1034/j.1600-0773.2002.900605.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Type I diabetes is considered a multifactorial autoimmune process initiated by an environmental factor. There is evidence that reactive oxygen species are involved in destructing insulin-producing beta-cells. In mice, reactive oxygen species and nitric monoxide contribute to beta-cell damage in the non-obese diabetic strain developing spontaneously diabetes and in diabetes induced with multiple low doses of streptozotocin. Previously, we found that zinc sulfate induced metallothionein in pancreatic islets, protected beta-cells against streptozotocin toxicity in vitro, and prevented diabetes induced with multiple low doses of streptozotocin. Since metallothionein is known to scavenge hydroxyl radicals in cell-free systems, we hypothesize that the protective effect of zinc sulfate results from metallothionein induction scavenging hydroxyl radicals generated by multiple low doses of streptozotocin. Therefore, we studied whether levels of hydroxyl radicals are increased by streptozotocin in isolated islets in vitro. Here, we demonstrate basal and streptozotocin-stimulated hydroxyl radicals by electron spin resonance spectroscopy in combination with hydroxyl radical-specific spin trapping in islet homogenates. Furthermore, in islet cultures, streptozotocin augmented generation of reactive oxygen species as determined by fluorescence. Of the group of reactive oxygen species, the streptozotocin-augmented generation of hydrogen peroxide was also specifically determined. We conclude that streptozotocin-mediated hydroxyl radicals and generation of reactive oxygen species may be crucial effectors in beta-cell damage.
引用
收藏
页码:317 / 326
页数:10
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