Abstract
Background:
Defective leukocyte-endothelial interactions are observed in experimental diabetes and may reduce the capacity to mount an adequate inflammatory response. The present study investigated the effect of ascorbic acid, an inhibitor of free radical and glycated protein formation as well as an aldose reductase inhibitor, on leukocyte-endothelial interaction in alloxan-diabetic rats.
Methods:
Rats were rendered diabetic by alloxan injection (40 mg/kg; iv). After 30 days, diabetic and nondiabetic controls were supplemented for 12 days with ascorbic acid (50 or 200 mg/kg/day) or received saline by gavage. The number of rollers, stickers after zymosan-activated plasma (10%) or leukotriene B(4) (1 microM) applied topically, and migrated cells after local injection of carrageenan (100 microg) were determined in the venules of the internal spermatic fascia by intravital microscopy. Erythrocyte velocity and wall shear rate were determined as well. Reactive oxygen species formation by endothelial cells was measured in vivo by the same technique. Immunocytochemistry for ICAM-1 detection on the endothelium of the venules of the internal spermatic fascia was carried out in cross sections of the whole testis of the animals.
Results:
The reduced number of rollers, stickers and migrated cells, as well as the higher production of reactive oxygen species by endothelial cells in diabetic rats was corrected by ascorbic acid supplementation. The low immunoreactivity for ICAM-1 in the venules of diabetic rats was improved by ascorbic acid supplementation. Ascorbic acid supplementation did not interfere with erythrocyte velocity or wall shear stress. Ascorbic acid administered to control rats did not alter the parameters studied above.
Conclusion:
We conclude that ascorbic acid improves leukocyte-endothelial interaction in diabetic rats at least in part by restoring the expression of ICAM-1 in the venules of diabetic rats.
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