Combination therapy with an antioxidant and a corticosteroid prevents autoimmune diabetes in NOD mice.
Oxygen free radicals have been implicated as mediators of pancreatic islet beta cell damage in autoimmune, insulin-dependent diabetes mellitus (IDDM). In this study, we show that the antioxidant, probucol, produced only a small decrease in diabetes incidence in nonobese diabetic (NOD) mice, an animal model for human IDDM. However, combination of probucol with the antiinflammatory corticosteroid, deflazacort, produced an early synergistic effect, delaying diabetes onset by 3 weeks, and a later additive effect, decreasing diabetes incidence from 68% (17 of 25 mice) to 23% (6 of 26 mice, p < 0.005). Protection against diabetes by the combination of probucol and deflazacort was associated with a significant decrease in pancreatic islet infiltration by macrophages/lymphocytes (insulitis) and prevention of islet beta cell loss.
Rabinovitch
A
A
Department of Medicine, University of Alberta, Edmonton, Canada.
Suarez
W L
WL
Power
R F
RF
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D015994:Incidence; D007328:Insulin / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D011282:Pregnenediones / Q000008:administration & dosage* / Q000627:therapeutic use; D011341:Probucol / Q000008:administration & dosage* / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001786:Blood Glucose; D007328:Insulin; D011282:Pregnenediones; C021988:deflazacort; D011341:Probucol