[Role of oxidative stress in permeability changes observed in the microcirculation of diabetic rats in vivo].
OBJECTIVE
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.


METHODS
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).


RESULTS
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).


CONCLUSIONS
Reactive oxygen species are responsible for an increase in microvascular permeability likely by leukocyte-independent mechanisms.
Bonnardel-Phu
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Département de Biophysique, Hôpital F. Widal, 200, rue du Faubourg Saint-Denis, 75475 Paris Cedex 10.
Vicaut
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E
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002374:Catalase / Q000008:administration & dosage / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003925:Diabetic Angiopathies / Q000209:etiology* / Q000378:metabolism; D004357:Drug Synergism; D005119:Extravasation of Diagnostic and Therapeutic Materials; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006861:Hydrogen Peroxide / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress; D010431:Pentoxifylline / Q000494:pharmacology; D011341:Probucol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology
D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; C039217:fluorescein isothiocyanate bovine serum albumin; D012710:Serum Albumin, Bovine; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D016650:Fluorescein-5-isothiocyanate; D011341:Probucol; D010431:Pentoxifylline