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Reduced Peripheral Blood Mitochondrial DNA Copy Number as Identification Biomarker of Suspected Arsenic-Induced Liver Damage

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Abstract

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.

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Data Availability

The data that support the findings of this study, titled “Association and risk of peripheral blood mitochondrial DNA copy number with arsenic-induced liver damage,” are available from the corresponding author upon reasonable request.

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Funding

This study was supported by the National Natural Science Foundation of China (no. 81430077, no. U1812403).

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Qi Wang: participated in investigations, performed the research, collected and analyzed the data, visualized the data, drafted the paper, and performed statistical analysis. Lu Ma: participated in investigations, reviewed and edited the paper. Baofei Sun: participated in investigations, provided quality supervision. Aihua Zhang: conceived and designed the research, organizing investigations, performed data curation, reviewed and edited the paper, obtained research funding, provided administrative, technical, and material support, and supported the study.

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Correspondence to Aihua Zhang.

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Wang, Q., Ma, L., Sun, B. et al. Reduced Peripheral Blood Mitochondrial DNA Copy Number as Identification Biomarker of Suspected Arsenic-Induced Liver Damage. Biol Trace Elem Res 201, 5083–5097 (2023). https://doi.org/10.1007/s12011-023-03584-5

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