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Sesamin ameliorates doxorubicin-induced cardiotoxicity: involvement of Sirt1 and Mn-SOD pathway.
Toxicol Lett. 2014 Jan 13; 224(2):257-63.TL

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+Show Affiliations

The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24211423

Citation

Su, Suwen, et al. "Sesamin Ameliorates Doxorubicin-induced Cardiotoxicity: Involvement of Sirt1 and Mn-SOD Pathway." Toxicology Letters, vol. 224, no. 2, 2014, pp. 257-63.
Su S, Li Q, Liu Y, et al. Sesamin ameliorates doxorubicin-induced cardiotoxicity: involvement of Sirt1 and Mn-SOD pathway. Toxicol Lett. 2014;224(2):257-63.
Su, S., Li, Q., Liu, Y., Xiong, C., Li, J., Zhang, R., Niu, Y., Zhao, L., Wang, Y., & Guo, H. (2014). Sesamin ameliorates doxorubicin-induced cardiotoxicity: involvement of Sirt1 and Mn-SOD pathway. Toxicology Letters, 224(2), 257-63. https://doi.org/10.1016/j.toxlet.2013.10.034
Su S, et al. Sesamin Ameliorates Doxorubicin-induced Cardiotoxicity: Involvement of Sirt1 and Mn-SOD Pathway. Toxicol Lett. 2014 Jan 13;224(2):257-63. PubMed PMID: 24211423.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sesamin ameliorates doxorubicin-induced cardiotoxicity: involvement of Sirt1 and Mn-SOD pathway. AU - Su,Suwen, AU - Li,Qian, AU - Liu,Yi, AU - Xiong,Chen, AU - Li,Junxia, AU - Zhang,Rong, AU - Niu,Yujie, AU - Zhao,Lijuan, AU - Wang,Yongli, AU - Guo,Huicai, Y1 - 2013/11/05/ PY - 2013/07/04/received PY - 2013/09/26/revised PY - 2013/10/28/accepted PY - 2013/11/12/entrez PY - 2013/11/12/pubmed PY - 2014/2/7/medline KW - 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide KW - Cardiotoxicity KW - DOX KW - Doxorubicin KW - MDA KW - MTT KW - Manganese SOD KW - Mn-SOD KW - ROS KW - Ses KW - Sesamin KW - Sirt1 KW - Sirtuin 1 KW - doxorubicin KW - malondialdehyde KW - reactive oxygen species KW - sesamin SP - 257 EP - 63 JF - Toxicology letters JO - Toxicol. Lett. VL - 224 IS - 2 N2 - 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. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/24211423/Sesamin_ameliorates_doxorubicin_induced_cardiotoxicity:_involvement_of_Sirt1_and_Mn_SOD_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(13)01386-6 DB - PRIME DP - Unbound Medicine ER -