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陈含笑, 王欣雨, 郁彪, 冯传林, 程国峰, 张磊, 王君君, 汪滢, 郭若文, 纪新苗, 谢文静, 陈卫丽, 宋超, 张欣. 2024: 稳态磁场减轻对乙酰氨基酚过量引起的急性肝损伤. 动物学研究: 478-490. DOI: 10.24272/j.issn.2095-8137.2023.410
引用本文: 陈含笑, 王欣雨, 郁彪, 冯传林, 程国峰, 张磊, 王君君, 汪滢, 郭若文, 纪新苗, 谢文静, 陈卫丽, 宋超, 张欣. 2024: 稳态磁场减轻对乙酰氨基酚过量引起的急性肝损伤. 动物学研究: 478-490. DOI: 10.24272/j.issn.2095-8137.2023.410
Han-Xiao Chen, Xin-Yu Wang, Biao Yu, Chuan-Lin Feng, Guo-Feng Cheng, Lei Zhang, Jun-Jun Wang, Ying Wang, Ruo-Wen Guo, Xin-Miao Ji, Wen-Jing Xie, Wei-Li Chen, Chao Song, Xin Zhang. 2024. Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field. Zoological Research, 45(3): 478-490. DOI: 10.24272/j.issn.2095-8137.2023.410
Citation: Han-Xiao Chen, Xin-Yu Wang, Biao Yu, Chuan-Lin Feng, Guo-Feng Cheng, Lei Zhang, Jun-Jun Wang, Ying Wang, Ruo-Wen Guo, Xin-Miao Ji, Wen-Jing Xie, Wei-Li Chen, Chao Song, Xin Zhang. 2024. Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field. Zoological Research, 45(3): 478-490. DOI: 10.24272/j.issn.2095-8137.2023.410

稳态磁场减轻对乙酰氨基酚过量引起的急性肝损伤

Acetaminophen overdose-induced acute liver injury can be alleviated by static magnetic field

  • 摘要: 对乙酰氨基酚(APAP)是世界上最常用的轻度镇痛解热药物。美国46%的急性肝衰竭和欧洲40%–70%的急性肝衰竭都是由其过量使用所引起。然而,目前被批准的治疗药物仅有抗氧化剂N-乙酰半胱氨酸(NAC),且对晚期肝损伤效果不佳。本研究通过使用不同APAP药物剂量诱导的肝损伤模型及多种磁场处理方式,探究了稳态磁场对药物性肝损伤的影响及机制。结果显示中等强度稳态磁场(SMF)处理可将大剂量APAP小鼠的死亡率从40%降低至0%,且在肝损伤早期和肝恢复后期均有作用。在肝损伤早期,稳态磁场能有效降低APAP诱导的氧化应激,降低自由基水平并减轻肝损伤。多种氧化应激标志物均有降低,同时抗氧化剂谷胱甘肽(GSH)水平升高。在肝脏恢复后期,竖直向下方向的稳态磁场可以促进DNA合成和肝细胞增殖。此外,即使在APAP过量后的24小时,NAC和稳态磁场联合使用也能显著降低高剂量APAP引起的肝损伤,并促进肝脏恢复。因此,我们的研究提供了一种非侵入、非药物的物理工具,在APAP过量后的肝损伤和肝修复阶段均可发挥改善作用。稳态磁场有望作为NAC的替代手段,或与NAC联用以预防或减轻APAP或其他药物过量引起的肝损伤。

     

    Abstract: Acetaminophen (APAP), the most frequently used mild analgesic and antipyretic drug worldwide, is implicated in causing 46% of all acute liver failures in the USA and between 40% and 70% in Europe. The predominant pharmacological intervention approved for mitigating such overdose is the antioxidant N-acetylcysteine (NAC); however, its efficacy is limited in cases of advanced liver injury or when administered at a late stage. In the current study, we discovered that treatment with a moderate intensity static magnetic field (SMF) notably reduced the mortality rate in mice subjected to high-dose APAP from 40% to 0%, proving effective at both the initial liver injury stage and the subsequent recovery stage. During the early phase of liver injury, SMF markedly reduced APAP-induced oxidative stress, free radicals, and liver damage, resulting in a reduction in multiple oxidative stress markers and an increase in the antioxidant glutathione (GSH). During the later stage of liver recovery, application of vertically downward SMF increased DNA synthesis and hepatocyte proliferation. Moreover, the combination of NAC and SMF significantly mitigated liver damage induced by high-dose APAP and increased liver recovery, even 24 h post overdose, when the effectiveness of NAC alone substantially declines. Overall, this study provides a non-invasive non-pharmaceutical tool that offers dual benefits in the injury and repair stages following APAP overdose. Of note, this tool can work as an alternative to or in combination with NAC to prevent or minimize liver damage induced by APAP, and potentially other toxic overdoses.

     

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