Antioxidant, probucol, can inhibit the generation of hydrogen peroxide in islet cells induced by macrophages and prevent islet cell destruction in NOD mice.
The preventive effect of antioxidant on the islet cell destruction in NOD mice was studied. Oral administration of probucol prevented the development of cyclophosphamide induced diabetes in NOD mice (incidence of diabetes; probucol: 0/10 vs. control: 9/15) As in vitro studies, the effects of probucol on the generation of H2O2 in the content of H2O2 in islet cells co-cultured with M phi were measured. Intracellular oxidation of 2'7'-dichlorofluorescin by H2O2 was analyzed by flow cytometry. The probucol-treated M phi induced less marked increase of H2O2 in islet cells in comparison with control M phi. The generation of H2O2 by M phi in islet cells from treated mice was less marked than that in controls. These results suggest that the preventive effect of probucol may be mediated by protection of islet cells from oxidative stress induced by M phi.
Fukuda
M
M
Department of Geriatric Medicine, Osaka University Medical School, Japan.
Ikegami
H
H
Kawaguchi
Y
Y
Sano
T
T
Ogihara
T
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002450:Cell Communication; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D011341:Probucol / Q000494:pharmacology*; D012016:Reference Values
D000975:Antioxidants; D006861:Hydrogen Peroxide; D011341:Probucol