Association of MRP2 expression level and arsenic methylation in rats' liver treated with sodium arsenite and sodium arsenate / 中国地方病学杂志

ABSTRACT

Objective To explore the effect of sodium arsenite (iAs3+) and sodium hydrogen arseuate (iAs5+) exposure on rat multidrug resistance protein 2 (MRP2) expression,and the correlation of liver arsenic and its methylation products,and to provide a basis for further elucidating the mechanism of arsenic toxicity.Methods Seventy wistar rats were randomly divided into seven groups,10 rats in each group.Control group was administrated with deionized water.Sodiun arsenite high-dose group,middle-dose group,low-dose group were administrated with different concentrations of sodium arsenite20.0,6.7 and 2.2 mg/kg BW every day,respectively.Animals were sacrificed 90 days later by cervical dislocation to collect liver,the expression of MRP2 in the membrane of hepatocyte was determined by Western blotting.HPLC-HGAFS was employed to determine the content or level of arsenic and its methylation products.Correlation between expression of MRP2 and arsenic methylation products was analyzed using Pearson's linear correlation method.Results The MRP2 protein levels of control group,iAs3+ and iAs5+ high-,middle-,low-dose groups were 1.21 ± 0.13,1.85 + 0.09,1.65 + 0.19,1.61 + 0.18,1.69 + 0.04,1.42 + 0.19,1.27 ± 0.10.Compared to control group,MRP2 protein levels of iAs3+ high-,middle-,low-dose group and iAs5+ high-dose group were increased (P ＜ 0.05); Compared with the low-dose group,MRP2 protein levels of iAs3+ and iAs5+ high dose groups were increased(P ＜ 0.05); Comparing the matched doses group of iAs5+ and iAs3+,MRP2 protein levels of iAs3+ high-,middle-,low-dose group were higher than iAs5+(P ＜ 0.05).Meanwhile,there was a significant positive relationship between the expression of MRP2 and the content of iAs3+,MMA and DMA in iAs3+ exposed group(r =0.575,0.678,0.395,all P ＜ 0.05).There was also a significant correlation between the expression of MRP2 and MMA and IMA in iAs5+ exposed group(r =0.593,0.643,all P ＜ 0.05).There was no significant relationship between the expression of MRP2 and the content of iAs5+in iAs5+ exposed group.Conclusions The expression of MRP2 is increased with increasing dose of arsenic exposure,thus resulting in compensatory changes on MRP2 expression in the liver cell membrane.MRP2 efflux may play an important role in the metabolic pathways of iAs3+.The level or load of arsenic methylation in liver is closely related with MRP2 expression.