Reversal of doxorubicin-induced vascular dysfunction by resveratrol in rat thoracic aorta: Is there a possible role of nitric oxide synthase inhibition?

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dc.contributor.authorOlukman, Murat
dc.contributor.authorCan, Cenk
dc.contributor.authorErol, Ayse
dc.contributor.authorOktem, Gulperi
dc.contributor.authorOral, Onur
dc.contributor.authorCinar, Mehtap Guelcihan
dc.date.accessioned2019-10-27T20:46:49Z
dc.date.available2019-10-27T20:46:49Z
dc.date.issued2009
dc.departmentEge Üniversitesien_US
dc.description.abstractObjective: The natural antioxidant, resveratrol has been suggested to protect against doxorubicin-induced cardiotoxicity. Although derangements in nitric oxide (NO) synthesis contribute to vascular endothelial dysfunction caused by doxorubicin, the effects of resveratrol on these parameters have not been evaluated yet. We investigated the impact of resveratrol on doxorubicin-induced vascular dysfunction in rat thoracic aorta with regard to NO synthesis in an experimental, prospective, controlled study. Methods: Wistar rats were assigned to 5 groups; doxorubicin (n=9), vehicle (dimethylsulphoxide) (n=8), resveratrol (n=8), doxorubicin+resveratrol (n=10), controls (n=9). Contractile and relaxant responses were evaluated on the isolated thoracic aortas. The expressions of endothelial (eNOS) and inducible (iNOS) isoforms of NO-synthase were also examined histopathologically on the aortas. Statistical analysis was performed by ANOVA for repeated measures for the response curves and one-way ANOVA for the pD(2) (-log EC50) and E-max (maximum phenylephrine contraction) values with subsequent Bonferroni test. Results: Doxorubicin (20 mg/kg, i.p), not only decreased the contractile responses to phenylephrine (p<0.001), but also attenuated the relaxant responses to acetylcholine (ACh)(p=0.002), calcium ionophore (A23187) (p=0.002) and sodium nitroprusside (SNP) (p=0.007). Immunohistochemistry revealed increased (p<0.05) eNOS and iNOS protein expressions after doxorubicin treatment. Coadministration of resveratrol (10 mg/kg/i.p.) reversed the increased expression of both NOS isoforms (p<0.05). Similarly, it prevented the doxorubicin-induced attenuation in ACh- (p=0.013) and A23187- (p=0.038) induced responses. In healthy rats the antioxidant did not cause significant changes. Conclusion: Prevention of excessive NO formation through eNOS and iNOS overexpression by resveratrol might contribute to the reversal of vascular endothelial dysfunction associated with doxorubicin treatment. (Anadolu Kardiyol Derg 2009, 9: 260-6)en_US
dc.identifier.endpage266en_US
dc.identifier.issn2149-2263
dc.identifier.issn2149-2271
dc.identifier.issue4en_US
dc.identifier.pmid19666426en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage260en_US
dc.identifier.urihttps://hdl.handle.net/11454/42463
dc.identifier.volume9en_US
dc.identifier.wosWOS:000269083200002en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakTR-Dizinen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTurkish Soc Cardiologyen_US
dc.relation.ispartofAnatolian Journal of Cardiologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectDoxorubicinen_US
dc.subjectvascular endothelial functionen_US
dc.subjectnitric oxideen_US
dc.subjectresveratrolen_US
dc.subjectraten_US
dc.titleReversal of doxorubicin-induced vascular dysfunction by resveratrol in rat thoracic aorta: Is there a possible role of nitric oxide synthase inhibition?en_US
dc.typeArticleen_US

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