title: Effect of alpha-phenyl-N-tert-butylnitrone on diabetes and lipid peroxidation in BB rats.
abstract: Oxygen free radicals have been shown to interfere with pancreatic islet beta cell function and integrity, and have been implicated in autoimmune type 1 diabetes. We hypothesized that the spontaneous autoimmune type 1 diabetes of the BB rat would be prevented by in vivo administration of a free-radical spin trap, alpha-phenyl-N-tert-butylnitrone (PBN). Twenty-eight diabetes-prone (BBdp) and 13 non-diabetes-prone (BBn) rats received PBN (10 mg/kg) subcutaneously twice daily, and 27 BBdp and 12 BBn rats received saline as controls. Rats were treated from age 47 +/- 6 days until diabetes onset or age 118 +/- 7 days. PBN caused no growth, biochemical, or hematological side effects. Sixteen control BBdp rats became diabetic (BBd, mean age 77 +/- 6 days) and six demonstrated impaired glucose tolerance (IGT rats). The incidence of diabetes and IGT was not different in PBN-treated BBdp rats. Saline-treated rats showed no differences in pancreatic malondialdehyde (MDA) contents of BBd, IGT rats, and the BBdp that did not develop diabetes, versus BBn rats (2.38 +/- 0.35 nmoL/g). Among rats receiving PBN, BBn had lower pancreatic MDA than BBd and IGT rats (1.38 +/- 0.15 vs. 1.88 +/- 0.15 and 2.02 +/- 0.24 nmoL/g, p < 0.05), but not than BBdp rats (1.78 +/- 0.12 nmoL/g, ns). BBn rats receiving PBN also had lower pancreatic MDA than the saline controls (p < 0.05). Thus, PBN is remarkably nontoxic and is able to decrease MDA in the absence of the autoimmune process, but does not prevent diabetes. A combination of PBN with other complementary antioxidant agents may hold better promise for disease prevention.
authors.affiliation: McGill Nutrition and Food Science Centre, Royal Victoria Hospital, Montréal, QC, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Iovino
authors.forename: S
authors.initials: S
authors.lastname: Kubow
authors.forename: E B
authors.initials: EB
authors.lastname: Marliss
mesh_terms: D000818:Animals; D003497:Cyclic N-Oxides; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D005951:Glucose Tolerance Test; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009589:Nitrogen Oxides / Q000494:pharmacology / Q000627:therapeutic use*; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB; D013113:Spin Labels
chemical_list: D003497:Cyclic N-Oxides; D009589:Nitrogen Oxides; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone; D008315:Malondialdehyde