PMID- 33542782 OWN - NLM STAT- MEDLINE DCOM- 20210902 LR - 20220426 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2021 DP - 2021 TI - Protective Effects of Oroxylin A against Doxorubicin-Induced Cardiotoxicity via the Activation of Sirt1 in Mice. PG - 6610543 LID - 10.1155/2021/6610543 [doi] LID - 6610543 AB - Doxorubicin- (DOX-) related cardiac injury impairs the life quality of patients with cancer. This largely limited the clinical use of DOX. It is of great significance to find a novel strategy to reduce DOX-related cardiac injury. Oroxylin A (OA) has been identified to exert beneficial effects against inflammatory diseases and cancers. Here, we investigated whether OA could attenuate DOX-induced acute cardiotoxicity in mice. A single dose of DOX was used to induce acute cardiac injury in mice. To explore the protective effects, OA was administered to mice for ten days beginning from five days before DOX injection. The data in our study indicated that OA inhibited DOX-induced heart weight loss, reduction in cardiac function, and the elevation in myocardial injury markers. DOX injection resulted in increased oxidative damage, inflammation accumulation, and myocardial apoptosis in vivo and in vitro, and these pathological alterations were alleviated by treatment of OA. OA activated the sirtuin 1 (Sirt1) signaling pathway via the cAMP/protein kinase A, and its protective effects were blocked by Sirt1 deficiency. OA treatment did not affect the tumor-killing action of DOX in tumor-bearing mice. In conclusion, OA protected against DOX-related acute cardiac injury via the regulation of Sirt1. CI - Copyright (c) 2021 Wen-Bin Zhang et al. FAU - Zhang, Wen-Bin AU - Zhang WB AUID- ORCID: 0000-0003-2463-6030 AD - Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China. FAU - Zheng, Yong-Fa AU - Zheng YF AUID- ORCID: 0000-0001-9273-5001 AD - Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China. FAU - Wu, Yao-Gui AU - Wu YG AUID- ORCID: 0000-0002-3051-7778 AD - Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China. LA - eng PT - Journal Article DEP - 20210119 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Cardiotonic Agents) RN - 0 (Flavonoids) RN - 53K24Z586G (5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one) RN - 80168379AG (Doxorubicin) RN - EC 3.5.1.- (Sirt1 protein, mouse) RN - EC 3.5.1.- (Sirtuin 1) SB - IM CIN - Oxid Med Cell Longev. 2022 Apr 14;2022:9862524. PMID: 35464757 MH - Animals MH - Cardiotonic Agents/pharmacology MH - Cardiotoxicity/genetics/metabolism/*prevention & control MH - Cells, Cultured MH - Cytoprotection/drug effects/genetics MH - Doxorubicin/*adverse effects MH - Flavonoids/*pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Myocytes, Cardiac/drug effects/physiology MH - Oxidative Stress/drug effects/genetics MH - Signal Transduction/drug effects/genetics MH - Sirtuin 1/genetics/metabolism PMC - PMC7840263 COIS- The authors declare that they have no conflicts of interest. EDAT- 2021/02/06 06:00 MHDA- 2021/09/03 06:00 PMCR- 2021/01/19 CRDT- 2021/02/05 05:59 PHST- 2020/11/01 00:00 [received] PHST- 2020/12/11 00:00 [revised] PHST- 2020/12/23 00:00 [accepted] PHST- 2021/02/05 05:59 [entrez] PHST- 2021/02/06 06:00 [pubmed] PHST- 2021/09/03 06:00 [medline] PHST- 2021/01/19 00:00 [pmc-release] AID - 10.1155/2021/6610543 [doi] PST - epublish SO - Oxid Med Cell Longev. 2021 Jan 19;2021:6610543. doi: 10.1155/2021/6610543. eCollection 2021.