Distribution Of Arsenic Species In Liver And Brain Of Mice In Their Early Developmental Stages Exposed To Arsenite And Arsenate Through Mother Mice

IntroductionGestation in humans and most rodents is a period of high sensitivity to chemical toxicity.Studies showed that after administration of iAs during gestation it can readily cross the placenta barrier and enter the fetal body.After birth the pups may continually expose to arsenicals through the milk of their mother or taken up directly from drinking water.To observe the distribution and metabolism of arsenic speciation in the brain and liver of mice in their early developmental stages exposed to in drinking water directly or through their mother,and to explore the difference of methylation of different valence state of inorganic arsenic(iAs)in the brain and liver of mice in their early developmental stages and the difference of hindrance arsenicals to across to the placenta barrier and breast barrier and blood brain barrier(BBB).MethodsMother mice were exposed to iAs~Ⅲor iAs~Ⅴin drinking water through gestation and lactation,and the concentrations of iAs~Ⅲor iAs~Ⅴwere 0,10mg/L and 30 mg/L. Their pups drank the same water continually after lactation.Tissues of brain and liver of mother mice and their pups aged 0,10,15,21 and 35 days after birth were taken to assess the levels of inorganic arsenic(iAs),monomethylarsenic acid(MMA), dimethylarsenic acid(DMA)by hydride generation trapping by ultra-hypothermia coupled with atomic absorption spectrometry.ResultsLevels of iAs,MMA and DMA in liver and levels of iAs and DMA in brain of mother mice increased along with the concentrations of iAs~Ⅲor iAs~Ⅴin drinking water. Levels of arsenic speciation in liver and brain of mother mice exposed to 10 mg/L iAs~Ⅴwere lower obviously than those in group exposed to 10 mg/L iAs~Ⅲ(P＜0.05). However,levels of arsenic speciation in liver and brain of mother mice had no difference between 30 mg/L iAs~Ⅴand 30 mg/L iAs~Ⅲexposed groups(P＞0.05).Levels of DMA in liver and brain of pups aged 0 days increased along with the iAs concentration in drinking water.Levels of DMA in liver and brain of pups aged 0 days exposed to 10 mg/L iAs~Ⅴwere lower obviously than those in group exposed to 10 mg/L iAs~Ⅲ(P＜0.05).Levels of DMA in liver and brain of pups aged 0 days did not differ significantly between 30 mg/L iAs~Ⅴand 30 mg/L iAs~Ⅲexposed groups(P＞0.05). Levels of DMA in liver and brain of pups aged 10 days increased along with the iAs concentration in drinking water;however,there were no difference between all iAs~Ⅲexposed groups and iAs~Ⅴexposed groups(P＞0.05).Levels of iAs and DMA in liver and brain of pups aged 15 days increased along with the iAs concentration in drinking water.Levels of iAs in liver of pups aged 15 days exposed to 10 mg/L iAs~Ⅴwere lower obviously than those in group exposed to 10 mg/L iAs~Ⅲ,and the levels of iAs and DMA in liver and brain of pups aged 15 days exposed to 30 mg/L iAs~Ⅴwere lower obviously than those in group exposed to 30 mg/L iAs~Ⅲ(P＜0.05).Levels of iAs, MMA and DMA in liver and levels of iAs and DMA in brain of pups aged 21 days increased along with the iAs concentration in drinking water.Levels of arsenic speciation in liver and brain of pups aged 21 days had no difference between all iAs~Ⅴexposed groups and iAs~Ⅲexposed groups(P＞0.05).Levels of iAs,MMA and DMA in liver and the levels of iAs and DMA in brain of pups aged 35 days increased along with the iAs concentration in drinking water.Levels of arsenic speciation in liver,levels of DMA in brain of pups aged 35 days in 10 mg/L iAs~Ⅴexposed groups were lower obviously than those in 10 mg/L iAs~Ⅲexposed groups,and levels of DMA in liver and brain of pups aged 35 days in 30 mg/L iAs~Ⅴexposed groups were lower obviously than those in 30 mg/L iAs~Ⅲexposed groups(P＜0.05).Levels of iAs,MMA and DMA in liver and brain of pups aged 10 days were lowest,and the main arsenic speciation was DMA.Levels of DMA in liver and brain of pups aged 0 days was high,and the main arsenic speciation was DMA,levels of iAs and DMA were low.Levels of iAs in liver and brain increased suddenly from pups aged 15,and the main arsenic speciation was iAs,levels of MMA and DMA were low. Levels of iAs,MMA and DMA in liver of pups aged 21 increased sharply,especially for MMA and DMA,and the main arsenic speciation were MMA and DMA;levels of iAs and DMA in brain increased obviously,and the main arsenic speciation were iAs and DMA.Levels of iAs,MMA and DMA in liver of pups aged 35 were the highest, and the main arsenic speciation were MMA and DMA,however,only the levels of DMA in brain significantly increased,and the main arsenic speciation were DMA. Levels of MMA in brain of all pups in their early developmental stages were very low.ConclusionsBoth iAs~Ⅲand iAs~Ⅴtaken up from the drinking water was mainly distributed and metabolized in the liver of mother mice and their pups.iAs~Ⅲtaken up in low levels might be accumulated and metabolized easily in the liver and brain as comparing with those of iAs~Ⅴ.However,during gestation and lactation,the main arsenic speciation transferred from mother mice was DMA.Compared to the placenta barrier,breast barrier could more effectually prevent arsenic speciation from entering into puppy's body.Both iAs and DMA seem to cross immature blood brain barrier(BBB)freely. However,mature BBB could effectually hinder iAs and partly block DMA from entering into the brain of pups and mother mice.It was in more dangerous for pups expose to iAs directly after birth for increasing the exposure of iAs in brain.