Oxidative damage in cerebral vessels of diabetic db/db mice.

BACKGROUND: Oxidative stress in diabetes mellitus has recently received increasing attention as it has been proven to be associated with the development of diabetic vascular complications. Our aim was to examine whether microvascular changes, including oxidative damage, were induced in the brains of diabetic animals. METHODS: The expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, the binding of cationized ferritin, a marker for evaluating endothelial glycocalyx, to the endothelial cells of capillaries and vascular permeability of intravenously injected horseradish peroxidase were examined in the cortices of 12- and 20-week-old db/db and db/+m mice. RESULTS: Immunostaining for 8-OHdG was clearly seen in the vessels of the cortex of 20-week-old db/db mice, but was hardly seen in those of mice in the other groups. The immunopositive area of 8-OHdG was significantly increased in the cortex of 20-week-old db/db mice compared with that of 20-week-old db/+m mice. No extravasated leakage of horseradish peroxidase was seen in any groups of mice, while the numbers of cationized ferritin particles binding to the endothelial cells was significantly decreased in 12- and 20-week-old db/db mice compared with that of db/+m mice at the same age, respectively. CONCLUSION: These findings suggest that changes in endothelial glycocalyx are induced in db/db mice and, in addition, the long-term diabetic condition of these mice induces oxidative DNA damage to the cerebral vessels.