Relationship Between Arsenic Methylation and Oxidative Stress in Mice Liver Induced by Arsenic Trioxide

Objective To investigate the relationship between arsenic methylation and oxidative stress in the liver of mice induced by arsenic trioxide(As₂O₃).

Methods Forty healthy KM mice were randomly divided into a control group(0.9% saline) and three arsenic groups treated with As₂O₃(1.0, 2.0 and 4.0 mg/kg) by gastric perfusion for 5weeks. The content of inorganic arsenics(As³⁺ and As⁵⁺), mono-methyl arsine(MMA) and dimethyl arsine(DMA) in liver were determined by high efficiency liquid chromatography and hydride genesis atomic fluorescence spectroscopy (HPLC-HGAFS) and the proportion of the those were calculated.The indexes of arsenic methylation including PMI and SMI were calculated. The activity of SOD and the levels of MDA, GSH and T-AOC were tested by kits.

Results With increasing the treated dosage of As₂O₃, the contents of arsenic metabolites and arsenic methylation in liver were significantly increased(P < 0.001). The level of MDA in the arsenic groups was significantly higher than that in the control group(P < 0.001), while the levels of GSH, SOD and T-AOC were lower significantly than the control group(P < 0.001). In the 1mg/kg As₂O₃ group, PMI was negatively correlated with T-AOC(P < 0.05), SMI was also negatively correlated with GSH and SOD(P < 0.05). In the 2 mg/kg As₂O₃ group, both PMI and SMI were positively correlated with MDA(P < 0.05), while negatively correlated with GSH and SOD(P < 0.05). In the 4 mg/kg As₂O₃ group, PMI was positively correlated with MDA(P < 0.05), while PMI and SMI were negatively correlated with GSH and SOD(P < 0.05).

Conclusion The arsenic methylation in liver was increased with higher treated dosage of arsenic trioxide, which might aggravate the oxidative stress of liver in mice.