The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, 550025, Guizhou, People's Republic of China.
Biol Trace Elem Res. 2023 Nov;201(11):5083-5097. doi: 10.1007/s12011-023-03584-5. Epub 2023 Jan 31.
Arsenic (As) can cause liver damage and liver cancer and is capable of seriously affecting human health. Therefore, it is important to identify biomarkers of arsenic-induced liver damage. Mitochondria are key targets of hepatotoxicity caused by arsenic. The mitochondrial DNA copy number (mtDNAcn) is the number of mitochondrial DNA (mtDNA) copies in the genome. mtDNA is vulnerable to exogenous chemical attacks, thus causing mtDNAcn to change after exposure to environmental pollutants. Therefore, mtDNAcn can serve as a potential marker to identify and assess the risk of diseases caused by exposure to environmental pollutants. In this study, we selected 272 arsenicosis patients (155 cases without liver damage and 117 cases with liver damage) and 218 participants not exposed to arsenic (155 cases without liver damage and 63 cases with liver damage) as subjects to investigate the correlation between peripheral blood mtDNAcn and arsenic-induced liver damage, as well as the ability of peripheral blood mtDNAcn to identify and assess the risk of arsenic-induced liver damage. Peripheral blood mtDNAcn in patients with arsenic-induced liver damage is significantly decreased and negatively correlated with serum ALT, AST, and GGT levels. The decrease of peripheral blood mtDNAcn was associated with an increased risk of arsenic-induced liver damage. The receiver operating characteristic (ROC) curve analysis indicated that peripheral blood mtDNAcn could specifically identify patients with liver damage in the arsenicosis group. The decision tree C5.0 model was established to identify arsenicosis in all patients with liver damage. Peripheral blood mtDNAcn was included in the model and played the most important role in the identification of arsenic-induced liver damage. This study provided a basis for the identification and evaluation of arsenic-induced liver damage by peripheral blood mtDNAcn, indicating that peripheral blood mtDNAcn is expected to be a potential biomarker of arsenic-induced liver damage, and provides clues for exploring the mechanism of arsenic-induced liver damage from mitochondria damage.
砷（As）可导致肝损伤和肝癌，并严重影响人类健康。因此，确定砷诱导肝损伤的生物标志物非常重要。线粒体是砷引起肝毒性的关键靶标。线粒体 DNA 拷贝数（mtDNAcn）是基因组中线粒体 DNA（mtDNA）的拷贝数。mtDNA 易受到外源性化学物质的攻击，因此暴露于环境污染物后 mtDNAcn 会发生变化。因此，mtDNAcn 可以作为一种潜在的标志物，用于识别和评估暴露于环境污染物引起的疾病的风险。在这项研究中，我们选择了 272 名砷中毒患者（155 名无肝损伤，117 名有肝损伤）和 218 名未接触砷的参与者（155 名无肝损伤，63 名有肝损伤）作为研究对象，以研究外周血 mtDNAcn 与砷诱导肝损伤之间的相关性，以及外周血 mtDNAcn 识别和评估砷诱导肝损伤风险的能力。砷诱导肝损伤患者外周血 mtDNAcn 显著降低，与血清 ALT、AST 和 GGT 水平呈负相关。外周血 mtDNAcn 的降低与砷诱导肝损伤的风险增加有关。受试者工作特征（ROC）曲线分析表明，外周血 mtDNAcn 可特异性识别砷中毒组中肝损伤患者。建立了决策树 C5.0 模型来识别所有有肝损伤的砷中毒患者。外周血 mtDNAcn 包含在模型中，在识别砷诱导的肝损伤方面发挥了最重要的作用。本研究为外周血 mtDNAcn 识别和评估砷诱导肝损伤提供了依据，表明外周血 mtDNAcn 有望成为砷诱导肝损伤的潜在生物标志物，为从线粒体损伤角度探索砷诱导肝损伤的机制提供了线索。
