The different methyl metabolic products of inorganic arsenic lead to various toxicities. Arsenic has been demonstrated to induce hepatotoxicity by oxidative stress. The relationship between hepatic injury and inorganic methylation is not yet known. This study was designed to explore the relationship between arsenic methylation and liver oxidative stress induced by arsenic trioxide (ATO). Forty healthy KM mice were randomly divided into control group (0.9% saline) and As₂O₃ (1.0 mg/Kg/day, 2.0 mg/Kg/day, 4.0 mg/Kg/day) groups with gastric perfusion for five weeks using high-efficiency liquid chromatography and hydride genesis atomic fluorescence spectroscopy (HPLC-HGAFS). The products of arsenic trioxiode methylating, including trivalent inorganic arsenic (iAs³⁺), pentavalent inorganic arsenic (iAs⁵⁺), mono methyl arsenic (MMA), and dimethyl arsenic (DMA) in the liver were determined. The indexes of arsenic methylation, including primary methyl index (PMI) and second methyl index (SMI) were calculated. The level of hepatic function and activity of MDA, GSH, SOD, and TAOC were detected with kits. We found that the remaining arsenic metabolic products in liver significantly increased with the increasing doses of arsenic trioxide and the liver function and oxidative stress deteriorated. Negative correlations were found between MMA%, PMI and GSH, SOD, and TAOC, while DMA% and SMI positively correlated with the levels of ALT and AST. PMI and SMI negatively correlated with TAOC, GSH, SOD, ALT, and AST, positively linked with the level of MDA. The present study demonstrates that the hepatotoxicity induced by the arsenic accounts for deteriorating oxidative injury activized by arsenic methylation metabolism, providing additional evidence to suggest a mechanism of arsenic poisoning. Therefore, reducing the process of arsenic methylation may be potentially benefical in treating and – more importantly – preventing arseniasis.
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