Generation of hydroxyl radicals mediated by streptozotocin in pancreatic islets of mice in vitro.
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.
Gille
Lars
L
German Diabetes Center, German Diabetes Research Institute at the Heinrich-Heine-University, Düsseldorf.
Schott-Ohly
Patricia
P
Friesen
Nadira
N
Schulte im Walde
Sabine
S
Udilova
Natascha
N
Nowl
Ham
H
Gleichmann
Helga
H
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002374:Catalase / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005296:Ferrous Compounds / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D004369:Pentetic Acid / Q000494:pharmacology; D013311:Streptozocin / Q000008:administration & dosage / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D000975:Antioxidants; D005296:Ferrous Compounds; D013481:Superoxides; D017665:Hydroxyl Radical; C020748:ferrous sulfate; D013311:Streptozocin; D004369:Pentetic Acid; D006861:Hydrogen Peroxide; D002374:Catalase