Role of oxidative stress in permeability changes observed in the microcirculation of diabetic rats in vivo
Bonnardel-Phu, E.; Vicaut, E.
Journal des Maladies Vasculaires 25(2): 115-121
2000
ISSN/ISBN: 0398-0499 PMID: 10804392 Document Number: 520326
Since an increase in the generation of free radicals has been shown in diabetes, we were interested on its involvement in changes in microvascular permeability during diabetes. Intravital microscopy was used to study changes in microvascular permeability during diabetes. The extravasation of a fluorescent macromolecular tracer (FITC-Albumin) was measured for one hour and, after computer-aided image analysis, was expressed as variations of normalized grey levels (arbitrary units). The extravasation of the tracer was increased in diabetic rats. An intravenous bolus of probucol (an other anti-oxidant) inhibits this increase (fig. 1). The increase of the extravasation of the macromolecular tracer can also be inhibited when both superoxide dismutase, (which dismutates superoxide to hydrogen peroxide) and catalase (which reacts with hydrogen peroxide to form water and molecular oxygen) are administered simultaneously (fig 2). When administered separately, these enzymes failed to inhibit the increase of the extravasation of the macromolecular tracer. Five-week treatment of diabetic rats by pentoxifyllin, a drug which inhibits leukocyte activation did not have any effect on the increase of albumin extravasation (fig. 3a). In addition, no difference was found in adherent leukocytes or in the leukocyte rolling flux between diabetic and normoglycemic rats (fig. 3b). Reactive oxygen species are responsible for an increase in microvascular permeability likely by leukocyte-independent mechanisms.