Titre du document / Document title
Angioprotective action of calcium dobesilate against reactive oxygen species-induced capillary permeability in the rat
Auteur(s) / Author(s)
BRUNET J. (1) ;
FARINE J.-C. (2) ;
GARAY R. P. (1) ;
HANNAERT P. (1) ;
Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)
(1) INSERM U400, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil, FRANCE
(2) O.M. Laboratories, Meyrin 2, Geneva, SUISSE
Résumé / Abstract
Calcium dobesilate possesses antioxidant properties in vitro, but the in vivo significance and putative angioprotective role of these properties are undefined. Here, calcium dobesilate was tested in a newly developed in vivo model of microvascular permeabilization induced by reactive oxygen species in the rat peritoneal cavity. In this model, microvascular permeabilization is equated to the rate of Evans blue extravasation toward the peritoneal cavity. Basal Evans blue extravasation (rate constant values k
e = 0.0176 ± 0.0015 h
-1) was markedly and significantly increased by reactive oxygen species generated in situ, with: (i) phenazine methosulfate/NADH (Δk
e(phenazine methosulfate) = 0.0419 ± 0.0043 h
-1) and (ii) xanthine/xanthine oxidase (Δk
e(XO) = 0.0383 ± 0.0010x h
-1). These actions of reactive oxygen species were abolished by locally injected superoxide dismutase (i.p., 300 units/kg). Intraperitoneally given calcium dobesilate (100 mg/kg) inhibited 75-100% of reactive oxygen species-induced Evans blue extravasation. By the intravenous route, calcium dobesilate i.v. (1-50 mg/kg) dose dependently inhibited phenazine methosulfate-induced Evans blue extravasation with an ID
50 of 2-5 mg/kg (full inhibition was reached at 20-50 mg/kg). After single oral administration, calcium dobesilate (5-500 mg/kg) dose dependently inhibited phenazine methosulfate-dependent Evans blue extravasation with an ID
50 of 50-100 mg/kg (81 % inhibition at 500 mg/kg, P < 0.003). After 7 days of oral calcium dobesilate (50 mg/kg once/day) phenazine methosulfate-induced Evans blue peritoneal extravasation was significantly reduced by half. These effects of calcium dobesilate were similar to those observed with a comparative antioxidant molecule, rutin. In conclusion, rat peritoneal microvascular permeability was strongly increased by reactive oxygen species, an effect that was significantly reduced by intraperitoneal, intravenous and oral calcium dobesilate. These results support the hypothesis that the antioxidant properties of calcium dobesilate could play a role in its angioprotective properties in vivo.
Revue / Journal Title
European journal of pharmacology
ISSN
0014-2999
CODEN EJPHAZ
Source / Source
1998, vol. 358, n
o3, pp. 213-220 (38 ref.)
Langue / Language
Anglais
Editeur / Publisher
Elsevier, Amsterdam, PAYS-BAS
(1967)
(Revue)
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Localisation / Location
INIST-CNRS, Cote INIST : 13322, 35400007149058.0050
Nº notice refdoc (ud4) : 1615902
