Probucol restores the defective leukocyte-endothelial interaction in experimental diabetes.
Defective leukocyte-endothelial interactions have been observed in experimental type 1 diabetes. One of the mechanisms involved in the late complications of diabetes mellitus is the formation of free radicals species. Antioxidant treatment has been demonstrated to have beneficial effects on the complications observed in this pathology. Using intravital microscopy to visualize venules of the internal spermatic fascia, we demonstrated that the defective leukocyte-endothelial interactions in alloxan-induced diabetic rats could be corrected by probucol treatment. The defects were quantitated by the number of leukocytes rolling along the venular endothelium, sticking to the venular wall after topical application of zymosan-activated plasma (10%-0.1 ml) or leukotriene B4 (1 microM/0.1 ml) and migrated after the application of a local irritant stimulus (carrageenan, 100 microg/0.1 ml). Leukocyte counts, erythrocyte velocity and venular shear rate, unaltered in diabetic rats, were not modified by this treatment. Reactive oxygen species formation by endothelial cells increased in diabetic preparations, and the reduced expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and P-selectin in cross-sections of the whole testis of the animals, were both restored by the antioxidant agent. Therefore, antioxidant treatment improves leukocyte-endothelial interaction in diabetic rats at least in part by restoring the expression of adhesion molecules in venules of diabetic rats.
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, Av Prof Lineu Prestes, 1524, Cidade Universitária, CEP:05508-900 São Paulo, Brazil.
Renata C O
RC
Zanardo
José W M C
JW
Cruz
Luis L
LL
Martinez
Maria Ap
MA
de Oliveira
Zuleica B
ZB
Fortes
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001775:Blood Circulation / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002464:Cell Migration Inhibition; D003921:Diabetes Mellitus, Experimental / Q000473:pathology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005456:Fluorescent Dyes; D006439:Hemodynamics / Q000187:drug effects; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007958:Leukocyte Count; D036904:Leukocyte Rolling / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D019007:P-Selectin / Q000378:metabolism; D010617:Phenanthridines; D011341:Probucol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016028:Receptors, Leukocyte-Adhesion / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects
D000975:Antioxidants; D001786:Blood Glucose; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D019007:P-Selectin; D010617:Phenanthridines; D016028:Receptors, Leukocyte-Adhesion; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; C058428:hydroethidine; D011341:Probucol