title: Sesamin ameliorates doxorubicin-induced cardiotoxicity: involvement of Sirt1 and Mn-SOD pathway.
abstract: Oxidative stress caused by doxorubicin (DOX) is believed to be a major underlying molecular mechanism of DOX-induced cardiotoxicity. Sesamin (Ses), an active component extracted from sesame seeds, exhibits antioxidative and anti-inflammatory effects. In the present study, possible protective mechanisms of Ses on DOX-induced cardiotoxicity were investigated in rats and cultured H9C2 cells. We demonstrated that Ses exhibits a significant protective effect on cardiac tissue in animal and cell models of DOX-induced cardiac injury. Moreover, Ses can ameliorate DOX-induced oxidative stress and mitochondrial damage. Further studies suggested that Ses is able to up-regulate the protein expression of Mn-SOD in normal rats and to restore the decreased expression of Mn-SOD in DOX-induced cardiac injury rats. Exposure to Ses or DOX alone slightly increased the protein expression of Sirt1; however, a more remarkable increase in Sirt1 protein level was detected in the Ses+DOX group. Treatment with a pan-sirtuin inhibitor (nicotinamide) or a Sirt1-specific inhibitor (EX-527) partially antagonised the effect of Ses on DOX-induced mitochondrial damage and completely abolished the effect of Ses on Mn-SOD expression. These findings indicate that the protective mechanisms of Ses on DOX-induced cardiotoxicity are involved in the alleviation of oxidative stress injury and Mn-SOD dysfunction, partially via the activation of Sirt1.
authors.affiliation: The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
authors.forename: Suwen
authors.initials: S
authors.lastname: Su
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Xiong
authors.forename: Junxia
authors.initials: J
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.forename: Yujie
authors.initials: Y
authors.lastname: Niu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhao
authors.forename: Yongli
authors.initials: Y
authors.lastname: Wang
authors.forename: Huicai
authors.initials: H
authors.lastname: Guo
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D004149:Dioxoles / Q000494:pharmacology*; D004317:Doxorubicin / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000502:physiology*; D013482:Superoxide Dismutase / Q000502:physiology*
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D004149:Dioxoles; D017705:Lignans; D004317:Doxorubicin; D013482:Superoxide Dismutase; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; C054125:sesamin
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Cardiotoxicity; DOX; Doxorubicin; MDA; MTT; Manganese SOD; Mn-SOD; ROS; Ses; Sesamin; Sirt1; Sirtuin 1; doxorubicin; malondialdehyde; reactive oxygen species; sesamin