The Study On The Effects Of Sodium Arsenite And Sodium Hydrogen Arsenate To The Metabolic Enzyme And MRP2 In Rats

Objective:To futher explore the mechanism of arsenic toxicology and seek for the differences between sodium arsenite (iAS3+) and sodium hydrogen arsenate (iAS5+) meta-bolism by studing the influence on content of dihydrouracil dehydrogenas (NAD), purine-nucleoside phosphorylase (PNP),5,10-methylenetetrahydrofolate reductase (MTHFR), myeloperoxidase (MPO), multidrug-resistance assoeiated protein 2 (MRP2) in rats which treated with sodium arsenite and sodium hydrogen arsenate. Methods:Seventy wistar rats were divided randomly into seven groups,10 rats each group. Control group was administrated with deionized water. Sodium arsenite high dose group, middle dose group, low dose group were administrated with different concentrations of sodium arsenite:20.0, 6.7,2.2mg/kg BW every the day; Sodium arsenate high dose group, middle dose group, low dose group were administrated with different concentrations of sodium arsenate:20.0, 6.7,2.2mg As/kg BW every the day. Animals were sacrificed 90 days later by cervical dislocation to collect the blood and Liver, the content of NAD, PNP, MTHFR, MPO were detected by ELISA and expression of MRP2 in the membrane of hepatocyte was determined by Western blotting. Results:1.Comparing the content between control group and iAS5+ high dose group, the difference was statistically significant (P<0.05). The NAD content in the high dose group and middle dose group were significantly lower than the low dose group (P<0.05). But for iAS5+, the NAD content in the high dose was significantly lower than the low dose group (P<0.05). Comparing the matched doses group of iAS5+ and iAS3+, the NAD content of iAS3+ in the high dose group was significantly higher than iAS5+(P<0.05), but the NAD content of iAS3+ in the middle dose group was significantly lower than iAS5+(P<0.05).2.The PNP content of iAS3+ low dose group and iAS5+ middle dose group were higher than control group (P<0.05). Comparing the matched doses group of iAS5+ and iAS3+, the PNP content of iAS3+ high,middle dose group were lower than iAS'+, and the PNP content of iAS3+ low dose group were significantly lower than iAS5+ low dose group(P<0.05).3. Compared with the control group, MTHFR levels of iAS3+ high, middle and low dose group and iAS51 high dose group iAS5+ were increased(P<0.05); Comparing the matched doses group of iAS5+ and iAS3+, MTHFR content of iAS3+ high, middle and low dose group was higher than iAS5 (P<0.05).4. Comparing the content with control group, MPO levels of iAS3+ and iAS5 high, middle and low dose group were increased (P<0.05); Comparing the content between the same test substance and the low dose group, MPO levels of iAS3+ and iAS5+ the high dose group were lower (P<0.05); Comparing the matched doses group of iAS5+ and iAS3+, MPO content of iAS3+ high dose group was lower than iAS5+ (P<0.05).5. Compared to control group, MRP2 protein levels of iAS3+ high, middle, low dose group and iAS5+ high dose group were increased (P<0.05); Comparing the protein levels betweer the same test substance and the low dose group, MRP2 protein levels of iAS3+and iAS5+ high dose group 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). Conclusion:A certain content of iAS5+ in blood and liver can increase NAD activity, but high dose inhibites the activity of NAD, iAS3+ inhibites the activity of NAD mostly. Arsenic can increase activities of PNP, MTHFR, MPO in the liver. The expression of MRP2 is increased when arsenic dose is growing up. MRP2 expression of iAS3+ is higher than iAS5+, because they may have different discharge or transport pathway. Arsenic metabolism and toxicity in liver have close relationship with contents of NAD, PNP, MTHFR, MPO and MRP2 expression.