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谷胱甘肽对阿霉素诱导的人心脏祖细胞心脏毒性的保护作用

The Protective Role of Glutathione against Doxorubicin-Induced Cardiotoxicity in Human Cardiac Progenitor Cells.

作者信息

Lee Eun Ji, Jang Woong Bi, Choi Jaewoo, Lim Hye Ji, Park Sangmi, Rethineswaran Vinoth Kumar, Ha Jong Seong, Yun Jisoo, Hong Young Joon, Choi Young Jin, Kwon Sang-Mo

机构信息

Laboratory for Vascular Medicine and Stem Cell Biology, Department of Physiology, Medical Research Institute, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea.

Convergence Stem Cell Research Center, Pusan National University, Yangsan 50612, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Jul 28;24(15):12070. doi: 10.3390/ijms241512070.

Abstract

This study investigated the protective effect of glutathione (GSH), an antioxidant drug, against doxorubicin (DOX)-induced cardiotoxicity. Human cardiac progenitor cells (hCPCs) treated with DOX (250 to 500 nM) showed increased viability and reduced ROS generation and apoptosis with GSH treatment (0.1 to 1 mM) for 24 h. In contrast to the 500 nM DOX group, pERK levels were restored in the group co-treated with GSH and suppression of ERK signaling improved hCPCs' survival. Similarly to the previous results, the reduced potency of hCPCs in the 100 nM DOX group, which did not affect cell viability, was ameliorated by co-treatment with GSH (0.1 to 1 mM). Furthermore, GSH was protected against DOX-induced cardiotoxicity in the in vivo model (DOX 20 mg/kg, GSH 100 mg/kg). These results suggest that GSH is a potential therapeutic strategy for DOX-induced cardiotoxicity, which performs its function via ROS reduction and pERK signal regulation.

摘要

本研究调查了抗氧化药物谷胱甘肽(GSH)对阿霉素(DOX)诱导的心脏毒性的保护作用。用DOX(250至500 nM)处理的人心脏祖细胞(hCPCs)在接受GSH处理(0.1至1 mM)24小时后,活力增加,活性氧生成减少,细胞凋亡减少。与500 nM DOX组相比,GSH联合处理组的pERK水平得以恢复,并且抑制ERK信号传导可提高hCPCs的存活率。与先前结果相似,100 nM DOX组中未影响细胞活力的hCPCs功能降低通过与GSH(0.1至1 mM)联合处理得到改善。此外,在体内模型中(DOX 20 mg/kg,GSH 100 mg/kg),GSH可预防DOX诱导的心脏毒性。这些结果表明,GSH是一种针对DOX诱导的心脏毒性的潜在治疗策略,其通过减少活性氧和调节pERK信号发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52a4/10419046/41f331ab4060/ijms-24-12070-g001.jpg

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