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.