Effect of alpha-phenyl-N-tert-butylnitrone on diabetes and lipid peroxidation in BB rats

Citation
G. Iovino et al., Effect of alpha-phenyl-N-tert-butylnitrone on diabetes and lipid peroxidation in BB rats, CAN J PHYSL, 77(3), 1999, pp. 166-174
Citations number
64
Categorie Soggetti
Pharmacology & Toxicology
Journal title
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
ISSN journal
00084212 → ACNP
Volume
77
Issue
3
Year of publication
1999
Pages
166 - 174
Database
ISI
SICI code
0008-4212(199903)77:3<166:EOAODA>2.0.ZU;2-F
Abstract
Oxygen free radicals have been shown to interfere with pancreatic islet bet a cell function and integrity, and have been implicated in autoimmune type 1 diabetes. We hypothesized that the spontaneous autoimmune type I diabetes of the BE rat would be prevented by in vivo administration of a free-radic al 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 sid e effects. Sixteen control BBdp rats became diabetic (BBd, mean age 77 +/- 6 days) and six demonstrated impaired glucose tolerance (IGT rats). The inc idence of diabetes and IGT was not different in PBN-treated BBdp rats. Sali ne-treated rats showed no differences in pancreatic malondialdehyde (MDA) c ontents 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 salin e controls (p < 0.05). Thus, PBN is remarkably nontoxic and is able to decr ease MDA in the absence of the autoimmune process, but does not prevent dia betes. A combination of PEN with other complementary antioxidant agents may hold better promise for disease prevention.