Angioprotective action of calcium dobesilate against reactive oxygen species-induced capillary permeability in the rat
Identifieur interne : 000825 ( France/Analysis ); précédent : 000824; suivant : 000826Angioprotective action of calcium dobesilate against reactive oxygen species-induced capillary permeability in the rat
Auteurs : John Brunet [France] ; Jean-Claude Farine [Suisse] ; Ricardo P. Garay [France] ; Patrick Hannaert [France]Source :
- European Journal of Pharmacology [ 0014-2999 ] ; 1998.
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 ke=0.0176±0.0015 h−1) was markedly and significantly increased by reactive oxygen species generated in situ, with: (i) phenazine methosulfate/NADH (Δke(phenazine methosulfate)=0.0419±0.0043 h−1) and (ii) xanthine/xanthine oxidase (Δke(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 ID50 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 ID50 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.
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DOI: 10.1016/S0014-2999(98)00604-9
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Garay</name></author><author><name sortKey="Hannaert, Patrick" sort="Hannaert, Patrick" uniqKey="Hannaert P" first="Patrick" last="Hannaert">Patrick Hannaert</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:D9E7D966C9A68DF58E6C2D792348F3852F92A749</idno><date when="1998" year="1998">1998</date><idno type="doi">10.1016/S0014-2999(98)00604-9</idno><idno type="url">https://api.istex.fr/document/D9E7D966C9A68DF58E6C2D792348F3852F92A749/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">006616</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">006616</idno><idno type="wicri:Area/Istex/Curation">006616</idno><idno type="wicri:Area/Istex/Checkpoint">003A37</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">003A37</idno><idno type="wicri:doubleKey">0014-2999:1998:Brunet J:angioprotective:action:of</idno><idno type="wicri:Area/Main/Merge">00BA17</idno><idno type="wicri:Area/Main/Curation">00B304</idno><idno type="wicri:Area/Main/Exploration">00B304</idno><idno type="wicri:Area/France/Extraction">000825</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">Angioprotective action of calcium dobesilate against reactive oxygen species-induced capillary permeability in the rat</title><author><name sortKey="Brunet, John" sort="Brunet, John" uniqKey="Brunet J" first="John" last="Brunet">John Brunet</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>INSERM U400, Faculté de Médecine, 8 rue du Général Sarrail, 94010 Créteil Cédex</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Créteil Cédex</settlement></placeName></affiliation></author><author><name sortKey="Farine, Jean Claude" sort="Farine, Jean Claude" uniqKey="Farine J" first="Jean-Claude" last="Farine">Jean-Claude Farine</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>O.M. 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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 ke=0.0176±0.0015 h−1) was markedly and significantly increased by reactive oxygen species generated in situ, with: (i) phenazine methosulfate/NADH (Δke(phenazine methosulfate)=0.0419±0.0043 h−1) and (ii) xanthine/xanthine oxidase (Δke(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 ID50 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 ID50 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.</div></front></TEI><affiliations><list><country><li>France</li><li>Suisse</li></country><region><li>Île-de-France</li></region><settlement><li>Créteil Cédex</li></settlement></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Brunet, John" sort="Brunet, John" uniqKey="Brunet J" first="John" last="Brunet">John Brunet</name></region><name sortKey="Garay, Ricardo P" sort="Garay, Ricardo P" uniqKey="Garay R" first="Ricardo P" last="Garay">Ricardo P. Garay</name><name sortKey="Hannaert, Patrick" sort="Hannaert, Patrick" uniqKey="Hannaert P" first="Patrick" last="Hannaert">Patrick Hannaert</name><name sortKey="Hannaert, Patrick" sort="Hannaert, Patrick" uniqKey="Hannaert P" first="Patrick" last="Hannaert">Patrick Hannaert</name></country><country name="Suisse"><noRegion><name sortKey="Farine, Jean Claude" sort="Farine, Jean Claude" uniqKey="Farine J" first="Jean-Claude" last="Farine">Jean-Claude Farine</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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