title: Lazaroid antioxidant reduces incidence of diabetes and insulitis in nonobese diabetic mice.
abstract: Oxygen free radicals have been implicated as mediators of pancreatic islet beta cell damage in autoimmune, insulin-dependent diabetes mellitus (IDDM). We examined the effects of a potent antioxidant compound, U78518F, on the incidence of diabetes and pancreatic islet infiltration with lymphocytes and monocytes (insulitis) in the non-obese diabetic (NOD) mouse, an animal model for human IDDM. U78518F, administered to NOD mice from age 8 to 30 weeks, produced a dose-dependent decrease in diabetes incidence, from 89% (16/18 control NOD mice) to 61% (11/18 NOD mice treated with 2 mg/kg/day U78518F, p < 0.05) and 44% (8/18 NOD mice treated with 16 mg/kg/day U78518F, p < 0.005). Protection against diabetes was associated with significant decreases in pancreatic insulitis and prevention of beta cell loss in the U78518F-treated NOD mice. These results suggest that antioxidants may have therapeutic application in attempts to prevent immune-mediated islet beta cell damage and IDDM.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Rabinovitch
authors.forename: W L
authors.initials: WL
authors.lastname: Suarez
authors.forename: R F
authors.initials: RF
authors.lastname: Power
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000517:prevention & control; D016923:Cell Death / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000494:pharmacology*; D005260:Female; D015994:Incidence; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D010879:Piperazines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D005021:Ethylamines; D007328:Insulin; D010879:Piperazines; D011725:Pyridines; C072017:U 78518F