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Magnesium Isoglycyrrhizinate Alleviates Arsenic Trioxide-Induced Cardiotoxicity: Contribution of Nrf2 and TLR4/NF-κB Signaling Pathway
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2021-02-12 , DOI: 10.2147/dddt.s296405 Bin Zheng 1 , Yakun Yang 1 , Jinghan Li 1 , Jing Li 1 , Saijie Zuo 1 , Xi Chu 2 , Shan Xu 3 , Donglai Ma 1 , Li Chu 1, 4
Drug Design, Development and Therapy ( IF 4.7 ) Pub Date : 2021-02-12 , DOI: 10.2147/dddt.s296405 Bin Zheng 1 , Yakun Yang 1 , Jinghan Li 1 , Jing Li 1 , Saijie Zuo 1 , Xi Chu 2 , Shan Xu 3 , Donglai Ma 1 , Li Chu 1, 4
Affiliation
Purpose: Magnesium isoglycyrrhizinate (MgIG), a single stereoisomer magnesium salt of glycyrrhizic acid, has beneficial effects on the cardiovascular system through anti-inflammatory, anti-oxidation, and anti-apoptotic actions. However, MgIG has not been shown to provide protection against cardiotoxicity induced by arsenic trioxide (ATO). This study aims to demonstrate the protection of MgIG against ATO-induced cardiac toxicity in mice and to investigate the underlying mechanism.
Methods: A mouse cardiotoxicity model was established by administering 5 mg/kg ATO for 7 days. MgIG used in conjunction with the ATO to assess its cardioprotection.
Results: MgIG administration could significantly reduce reactive oxygen species generation and the changes in tissue morphology. Also, MgIG administration increased the activity of antioxidase, such as superoxide dismutase, catalase, and glutathione peroxidase, and reduced malondialdehyde content and pro-inflammatory cytokine levels. Western blotting showed decreased expression of Bcl-2 associated X protein and Caspase-3, with increased expression of B-cell lymphoma 2. Importantly, MgIG administration increased nuclear factor-erythroid-2-related factor 2 (Nrf2) expression, while the expressions of nuclear factor kappa-B (NF-κB) and toll-like receptor-4 (TLR4) were significantly decreased.
Conclusion: Our data showed that MgIG alleviates ATO-induced cardiotoxicity, which is associated to the anti-inflammation, anti-oxidation, and anti-apoptosis action, potentially through activation of the Nrf2 pathway and suppression of the TLR4/NF-κB pathway.
Keywords: magnesium isoglycyrrhizinate, arsenic trioxide, cardiotoxicity, Nrf2, TLR4/NF-κB
中文翻译：
异甘草酸镁减轻三氧化二砷引起的心脏毒性：Nrf2 和 TLR4/NF-κB 信号通路的贡献
用途：异甘草酸镁（MgIG）是甘草酸的单一立体异构体镁盐，通过抗炎、抗氧化和抗细胞凋亡作用对心血管系统产生有益作用。然而，MgIG 尚未被证明可以提供针对三氧化二砷 (ATO) 引起的心脏毒性的保护作用。本研究旨在证明 MgIG 对 ATO 诱导的小鼠心脏毒性具有保护作用，并探讨其潜在机制。
方法：采用5 mg/kg ATO给药7 d建立小鼠心脏毒性模型。 MgIG 与 ATO 联合使用来评估其心脏保护作用。
结果： MgIG 给药可以显着减少活性氧的产生和组织形态的变化。此外，施用 MgIG 可以增加抗氧化酶的活性，例如超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶，并降低丙二醛含量和促炎细胞因子水平。蛋白质印迹显示 Bcl-2 相关 X 蛋白和 Caspase-3 的表达降低，而 B 细胞淋巴瘤 2 的表达增加。重要的是，MgIG 给药增加了核因子 - 红细胞 - 2 相关因子 2 (Nrf2) 的表达，而表达核因子κ-B (NF-κB) 和Toll 样受体-4 (TLR4) 显着降低。
结论：我们的数据表明，MgIG 可能通过激活 Nrf2 通路和抑制 TLR4/NF-κB 通路来减轻 ATO 诱导的心脏毒性，这与抗炎、抗氧化和抗凋亡作用有关。
关键词:异甘草酸镁, 三氧化二砷, 心脏毒性, Nrf2, TLR4/NF-κB
更新日期：2021-04-20
Methods: A mouse cardiotoxicity model was established by administering 5 mg/kg ATO for 7 days. MgIG used in conjunction with the ATO to assess its cardioprotection.
Results: MgIG administration could significantly reduce reactive oxygen species generation and the changes in tissue morphology. Also, MgIG administration increased the activity of antioxidase, such as superoxide dismutase, catalase, and glutathione peroxidase, and reduced malondialdehyde content and pro-inflammatory cytokine levels. Western blotting showed decreased expression of Bcl-2 associated X protein and Caspase-3, with increased expression of B-cell lymphoma 2. Importantly, MgIG administration increased nuclear factor-erythroid-2-related factor 2 (Nrf2) expression, while the expressions of nuclear factor kappa-B (NF-κB) and toll-like receptor-4 (TLR4) were significantly decreased.
Conclusion: Our data showed that MgIG alleviates ATO-induced cardiotoxicity, which is associated to the anti-inflammation, anti-oxidation, and anti-apoptosis action, potentially through activation of the Nrf2 pathway and suppression of the TLR4/NF-κB pathway.
Keywords: magnesium isoglycyrrhizinate, arsenic trioxide, cardiotoxicity, Nrf2, TLR4/NF-κB
中文翻译：
异甘草酸镁减轻三氧化二砷引起的心脏毒性：Nrf2 和 TLR4/NF-κB 信号通路的贡献
用途：异甘草酸镁（MgIG）是甘草酸的单一立体异构体镁盐，通过抗炎、抗氧化和抗细胞凋亡作用对心血管系统产生有益作用。然而，MgIG 尚未被证明可以提供针对三氧化二砷 (ATO) 引起的心脏毒性的保护作用。本研究旨在证明 MgIG 对 ATO 诱导的小鼠心脏毒性具有保护作用，并探讨其潜在机制。
方法：采用5 mg/kg ATO给药7 d建立小鼠心脏毒性模型。 MgIG 与 ATO 联合使用来评估其心脏保护作用。
结果： MgIG 给药可以显着减少活性氧的产生和组织形态的变化。此外，施用 MgIG 可以增加抗氧化酶的活性，例如超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶，并降低丙二醛含量和促炎细胞因子水平。蛋白质印迹显示 Bcl-2 相关 X 蛋白和 Caspase-3 的表达降低，而 B 细胞淋巴瘤 2 的表达增加。重要的是，MgIG 给药增加了核因子 - 红细胞 - 2 相关因子 2 (Nrf2) 的表达，而表达核因子κ-B (NF-κB) 和Toll 样受体-4 (TLR4) 显着降低。
结论：我们的数据表明，MgIG 可能通过激活 Nrf2 通路和抑制 TLR4/NF-κB 通路来减轻 ATO 诱导的心脏毒性，这与抗炎、抗氧化和抗凋亡作用有关。
关键词:异甘草酸镁, 三氧化二砷, 心脏毒性, Nrf2, TLR4/NF-κB
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