Sacubitril/valsartan reduces endoplasmic reticulum stress in a rat model of doxorubicin-induced cardiotoxicity
DC Field | Value | Language |
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dc.contributor.author | Kim, Byung Sik | - |
dc.contributor.author | Park, In-Hwa | - |
dc.contributor.author | Lee, A-Hyeon | - |
dc.contributor.author | Kim, Hyun-Jin | - |
dc.contributor.author | Lim, Young-Hyo | - |
dc.contributor.author | Shin, Jeong-Hun | - |
dc.date.accessioned | 2022-07-06T06:27:38Z | - |
dc.date.available | 2022-07-06T06:27:38Z | - |
dc.date.created | 2022-03-07 | - |
dc.date.issued | 2022-04 | - |
dc.identifier.issn | 0340-5761 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/139011 | - |
dc.description.abstract | The induction of endoplasmic reticulum (ER) stress has been reported as a key contributor to the cardiotoxicity of doxorubicin. Previous in vitro and in vivo studies suggest that sacubitril/valsartan, a novel angiotensin receptor-neprilysin inhibitor, could be effective against doxorubicin-induced cardiotoxicity. However, the precise mechanisms are not fully understood. Therefore, we investigated whether the cardioprotective effects of sacubitril/valsartan are associated with ER stress modulation in a rat model of doxorubicin-induced cardiotoxicity. Male Sprague-Dawley rats were treated with intraperitoneal injections of doxorubicin (15 mg/kg; cumulative) or saline for 3 weeks. From the day before the first treatment, control animals were gavaged daily with water (n = 8), whereas doxorubicin-treated animals were gavaged daily with water (n = 8) or sacubitril/valsartan (60 mg/kg/day; n = 8) for 6 weeks. Echocardiography was performed 6 weeks after the initiation of doxorubicin. In addition, serum troponin I and N-terminal brain natriuretic peptide levels were determined, and the extent of apoptosis and protein levels related to ER stress in the cardiac tissue and doxorubicin-treated H9c2 cardiomyocytes were analyzed. Sacubitril/valsartan significantly reduced doxorubicin-induced cardiac dysfunction and apoptosis in the myocardium. In addition, sacubitril/valsartan significantly downregulated the expression levels of proteins related to apoptosis and ER stress, including BAX, caspase 3, GRP78, PERK, IRE-1 alpha, ATF-6, eIF-2 alpha, ATF-4, and CHOP, in the myocardium of a rat model of doxorubicin-induced cardiotoxicity in vivo and doxorubicin-treated H9c2 cardiomyocytes in vitro. Sacubitril/valsartan significantly alleviated doxorubicin-induced cardiotoxicity, which may be associated with the reduction of ER stress. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | SPRINGER HEIDELBERG | - |
dc.title | Sacubitril/valsartan reduces endoplasmic reticulum stress in a rat model of doxorubicin-induced cardiotoxicity | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Hyun-Jin | - |
dc.contributor.affiliatedAuthor | Lim, Young-Hyo | - |
dc.contributor.affiliatedAuthor | Shin, Jeong-Hun | - |
dc.identifier.doi | 10.1007/s00204-022-03241-1 | - |
dc.identifier.scopusid | 2-s2.0-85124765910 | - |
dc.identifier.wosid | 000754346500001 | - |
dc.identifier.bibliographicCitation | ARCHIVES OF TOXICOLOGY, v.96, no.4, pp.1065 - 1074 | - |
dc.relation.isPartOf | ARCHIVES OF TOXICOLOGY | - |
dc.citation.title | ARCHIVES OF TOXICOLOGY | - |
dc.citation.volume | 96 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 1065 | - |
dc.citation.endPage | 1074 | - |
dc.type.rims | ART | - |
dc.type.docType | Article; Early Access | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Toxicology | - |
dc.relation.journalWebOfScienceCategory | Toxicology | - |
dc.subject.keywordPlus | NEPRILYSIN INHIBITION | - |
dc.subject.keywordPlus | SYSTOLIC DYSFUNCTION | - |
dc.subject.keywordPlus | ENALAPRIL | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | DIAGNOSIS | - |
dc.subject.keywordPlus | FAILURE | - |
dc.subject.keywordPlus | LCZ696 | - |
dc.subject.keywordAuthor | Doxorubicin | - |
dc.subject.keywordAuthor | Cardiotoxicity | - |
dc.subject.keywordAuthor | Sacubitril | - |
dc.subject.keywordAuthor | valsartan | - |
dc.subject.keywordAuthor | Endoplasmic reticulum stress | - |
dc.identifier.url | https://link.springer.com/article/10.1007/s00204-022-03241-1 | - |
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