| Objective:To investigate the mechanism of arsenic toxicology further and seek for the difference between sodium arsenite and sodium arsenate(different valence state arsenic), we studied the influence on activity of biochemical indicator and Methyltransferase in rats liver mRNA treated with sodium arsenite and sodium arsenate. Methods:Different valence state and doses of arsenic was administrated with drinking water to Wistar rats, rats were divided into 7 group randomly,10 rats each group, control group (C) administer-ated with demineralized water, Sodium Arsenite low dose group(AL), medial dose group (AM), high dose group (AH) administrated with different concentrations of sodium arsen ite:20.0,6.7,2.2mg/kg; Sodium Arsenate low dose group(BL), medial dose group(BM), high dose group(BH) administrated with different concentrations of sodium Arsenate:20.0, 6.7,2.2mg/kg. Exposed by the free water method. Continuous exposed for 90d. At the end of the 3 months execute the rats by cervical dislocation to collect the blood and Liver, the activity of SAM, ARR, MTR was detected by ELISA in Rats liver, the activity of PK was detected by ELISA in rats blood, the expression of methyltransferase was detected by real-time PCR in liver genome mRNA. Results:1.iAs3+and iAs5+ can increase the activity of SAM in rats liver (P<0.05), with the increasing dose of arsenic, the tendency is descendent, the activity of iAs3+ is lower than iAs5+ in identical dose, the difference was statistically significant (P<0.05);2.ARR can change the activity of iAs3+ and iAs5+, the difference was statistically significant (P<0.05); to compare high and medial dose group with low dose group of iAs3+, the difference was statistically significant (P<0.05); to compare high dose group with low dose group of iAs5+, the difference was statistically significant (P<0.05); to compare iAs+and iAs5+, the difference of each experimental group was statistically significant (Ali P<0.05);3.MTR can change the activity of iAs3+and iAs+,the difference was statistically significant (P<0.05); to compare identical the test matter with low dose group, the difference was statistically significant (P<0.05); the difference of high dose group of iAs3+ and iAs5+ was statistically significant(P<0.05); to compare iAs3+ and iAs5+, the difference of high dose group of was statistically significant (P<0.05);4.iAs3+ and iAs5+ can decrease the activity of PK in rats blood (P<0.05), the difference of high dose group was statistically significant (P<0.05),the medial dose and low dose group was not statistically significant (All P>0.05);5.The result of real-time PCR showed that the difference of methyltransferase expression was statistically signif-icant (P<0.05) with control group in rats liver mRNA on iAs3+ and iAs5+; with the increase of Arsenic dose, iAs3+ As3MT mRNA showed a ascendant trend, iAs5+ As3MT mRNA showed a descendant trend; to compere with iAs3+and iAs5+ of high dose group of As3MT, the difference was statistically significant (P<0.05); with the increase of Arsenic dose, iAs3+ DNMT3A,3B mRNA showed a descendant trend, iAs5+DNMT3A,3B mRNA showed a ascendant trend, to compere with iAs3+and iAs5+ of high and low dose groups of DNMT3A,3B, the difference was statistically significant (P<0.05);the difference of DNMT1 of iAs3+ and iAs5+ high, medial dose group was statistically significant (P<0.05); Conclusions:1.iAs3+and iAs5+ can make the content of SAM step-up in rats liver, SAM offer abundant methyl donor to enhance metabolic capability of methylation.2. iAs3+or iAs5+ affect the activity of ARR, the activity of reductases will affect the processes of methylation directly.3. iAs3+ or iAs5+ can modify the vitality of MTR in rats to affect normal metabolism of folic acid and intra-cellular DNA methylation reaction and biosynthesis of deoxynucleotide triphosphate, then impact arsenical mechanism of action.4. Long-term intake overdose iAs3+ or iAs5+can decrease the vitality of PK to pass glycolysis and modify arsenic methylated level.5. Long-term and chronicity expose to iAs3+or iAs5+ can step-up As3MT mRNA expression, and exis dosage relationships, it will impact arsenical methylation level; iAs3+or iAs5+ can inhibit DNMTs mRNA expression in rats liver that indicate different valence state arsenic may inhibit DNMTs mRNA expression level and affect epigenetic regulation, then induce toxic effect generation. |
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