Strain differences in arsenic-induced oxidative lesion via arsenic biomethylation between C57BL/6J and 129X1/SvJ mice

Ruirui Wu,Guifan Sun,Yuanyuan Xu,Xiafang Wu,Huihui Wang,Jingbo Pi,Yongfang Li,Lanyue Gao,Xin Fang

doi:10.1038/srep44424

Abstract

Arsenic is a common environmental and occupational toxicant with dramatic species differences in its susceptibility and metabolism. Mouse strain variability may provide a better understanding of the arsenic pathological profile but is largely unknown. Here we investigated oxidative lesion induced by acute arsenic exposure in the two frequently used mouse strains C57BL/6J and 129X1/SvJ in classical gene targeting technique. A dose of 5 mg/kg body weight arsenic led to a significant alteration of blood glutathione towards oxidized redox potential and increased hepatic malondialdehyde content in C57BL/6J mice, but not in 129X1/SvJ mice. Hepatic antioxidant enzymes were induced by arsenic in transcription in both strains and many were higher in C57BL/6J than 129X1/SvJ mice. Arsenic profiles in the liver, blood and urine and transcription of genes encoding enzymes involved in arsenic biomethylation all indicate a higher arsenic methylation capacity, which contributes to a faster hepatic arsenic excretion, in 129X1/SvJ mice than C57BL/6J mice. Taken together, C57BL/6J mice are more susceptible to oxidative hepatic injury compared with 129X1/SvJ mice after acute arsenic exposure, which is closely associated with arsenic methylation pattern of the two strains.

Highlights

Arsenic is one of the most important pollutants ubiquitously existing in the natural and disposed by human activity[1]
We find that alteration of redox potential and hepatic oxidative injury induced by acute arsenic exposure vary in the two mouse strains, which cannot be fully explained by antioxidative response of the two mouse strains, but is closely related to their distinct arsenic methylation capacity
B6 mice showed a significant decrease in blood GSH/GSSG due to the elevation of GSSG levels at 24 h, while 129 mice did not showed any significant change of blood glutathione status (Fig. 1A–C)

Summary

Introduction

Arsenic is one of the most important pollutants ubiquitously existing in the natural and disposed by human activity[1]. Associations of chronic arsenic exposure with cardiovascular dysfunction, diabetes, respiratory symptoms, neurological defects, and reproductive issues have been reported[2,3] Another reason for the importance of arsenic in the toxicology field in that the occurrence of acute arsenic poisonings in homicide, suicide or accident[4,5]. We find that alteration of redox potential and hepatic oxidative injury induced by acute arsenic exposure vary in the two mouse strains, which cannot be fully explained by antioxidative response of the two mouse strains, but is closely related to their distinct arsenic methylation capacity

Methods

Results

Conclusion