The Relationship Between The Metabolites Of Arsenite Sodium And Arsenate Sodium And Related Metabolic Enzymes In Rat Kidneys

Objective:To analyze the effect of arsenic (arsenite sodium,iAs3+; iAs5+arsenate sodium on the arsenic metabolites and related metabolic enzymes,evaluate the different effects of arsenic valent state,analyze the relationship between metabolites and related metabolic enzymes and the gender differences and provide reference standard for the relationship between arsenic metabolism and arsenic toxicity.Methods:70Wistar rats were divided into7groups randomly (10rats in each group,5males and5females),including control group,low dose of iAs3+group(2.2mg/kg),medium dose of iAs3+group(6.7mg/kg),high dose of iAs’+group(20.0mg/kg).90days later,the rat kidneys were obtained and stored at-80℃. High performance liquid chromatography and hydride genesis atomic fluorescence spectroscopy(HGAS)was used to determine arsenic metabolites and calculated the values of PMI and SMI. Kit methods were used to detect and analyze the concentration or activity of related metabolic enzymes,the relationship between arsenic metolites and related metabolic enzymes and gender differences.Results:1.After iAs3+and iAs5+exposured, the weight of rats in each group showed normal growth state,the medium dose of arsenate sodium can promote the weight of rats in second and third month.Renal pathology indicated that the apoptotic effect of iAs5+groups was more significant than iAs3+groups with different doses.High dose group of iAs5+made some rats renal tubular epithelial nucleus disappear and caused cells to die.2.The low, medium and high dose of iAs3+groups were higher than the same dose levels of iAs5+groups (P<0.05);3.The content of GSH in each arsenic groups was dose-dependent.The activity of GST in low,medium,high dose of iAs3+groups were increased with dose in rat kidneys,which were contrary to the iAs5+groups.4.The concents of GSH were negative related with the contents of MMA in iAs3+groups(r were-0.636、-0.867and-0.918,respectively, all P<0.05).There were no significant correlation between concentration of rats renal DMA and GST activity(P>0.05)in all groups.The correlation of contents of MMA and DMA and TAs,related metabolic enzymes in high dose of arsenic groups were not significant(P>0.05).5.In iAs5+group,the PMI of male rats was higher than the famale,both genders were dose-dependent,the SMI of male rats was also higher than the female in low,medium dose group of iAs5+(P<0.05).Conclusions:1.The medium dose of iAs5+group can promote the weight of rats.2.The adverse effect on rats renal tubular epithelial cells of iAs5+were more significant than iAs3+,high dose of iAs5+can cause nucleus to disappear and damage3.The first methylation capacity of male rat kidneys was stronger than female rats in iAs3+groups;The first methylation capacity in kidney of female rats was stronger than the male which all exposure to iAs5+.The methylation capacity in kidey of different gerders was different,these may caused by the different arsenic metabolism pathway of valence states of arsenic and different site or target organ acculation in rat kidneys.4. Exposure to arsenic can enhance the activity of GST and decline the contents of GSH,the concentration of GSSG in iAs5+groups than iAs3+groups;And the acvtivity of Methyl transferase of different genders in iAs5+groups were higher than iAs3+groups,and the contents of GSH in iAs5+groups were higher than iAs3+groups in males kidneys.5. Different valence states of arsenic and its metabolites likely can cause the changes in levels of enzymes,which may be the basis of metabolism of arsenic toxicity in iAs3+and iAs5+.