This study showed that citiolone (CIT), a free radical scavenger, sign
ificantly increased superoxide dismutase (P < 0.001 vs. untreated NOD,
NMMA-treated, and silica-treated animals), catalase (P < 0.01 vs. unt
reated NOD), and glutathione peroxidase (P < 0.001 vs. untreated NOD a
nd C57BL6/J) values. Silica treatment was capable of counteracting the
plasma antioxidant capacity (TRAP) decrease observed in untreated NOD
mice, although it did not block the blood glucose rise and insulitis
progression in type 1 diabetes significantly. Conversely, early silica
administration was able to deplete macrophages (as demonstrated by im
munocytochemistry) and to block the rise in blood glucose levels and i
nsulitis progression significantly. Silica-treated animals in this stu
dy showed the highest TRAP levels, demonstrating that depletion of mac
rophages also was able to improve the antioxidant status. This study s
uggested that macrophages are essential for type 1 diabetes developmen
t and showed that they also are involved when the antioxidant status i
s affected. The reported findings are significant in view of previous
studies indicating that oxygen and/or nitrogen free radicals contribut
e to the islet beta-cell destruction in type 1 diabetes animal models.
(C) 1998 Wiley-Liss, Inc.