| Objective:1. Dynamic observation the changes of arsenic associated metabolism enzyme gene expression and the relation between these gene expression and arsenic levels in mice liver treated with low level arsenic.2. Dynamic observation the effects of low level arsenic on oxidative stress of liver in mice.Method:Health 96 male KM mouse were randomly divided into 4 groups. Mice were treated with arsenite at 0, 50, 500, 5000μg/L in the drinking water and each group had three-time exposure: 4, 6 and 8 weeks. Then the mice were killed and liver and renal were collected. The general toxicicities(body weight, water consumption, food consumption, and main organ index)were observed. The total arsenic of blood, liver and renal were determined by atomic fluorescence spectrometry(AFS). The contents of malondial dehyde(MDA), activity of Glutathione peroxidases(GSH-Px), activity of superoxide dismutase(SOD) ,and the gene expression of the arsenic metabolic enzymes(PNP, GSTO, AS3MT) of liver were determined. The variance analysis was conducted with SPSS 13.0 statistic software.Results:1. There were not significantly differences in water consumption and food consumption in different time and dose (P >0.05);The body weight was significantly increase in 50 and 500μg/L on 4 weeks, but decreased in 5000μg/L on 8 weeks. Liver and renal index were increase then decrease as the time and dose were increasing, and there were significantly(P<0.05). Spleen and heart index were increase significantly as the time and dose were increasing(P<0.05), there was not significantly in brain index(P>0.05), lung index was increase in middle dose(P<0.05), but not change in low and high dose(P >0.05).2. The total arsenic in blood, liver and renal were gradually increase with the time and dose were increasing, but there was not significantly in short time(P>0.05), there was significantly increase in low, middle and high dose on longer time(P <0.05). The accumulation of arsenic was mainly in liver and the change trends of blood arsenic, liver arsenic and renal arsenic were the same.3. The MDA is significantly increased between arsenite exposure and control. GSH-Px and SOD were increase significantly in low dose and short time(P <0.05), but as the time and dose growing, the activities were decreased, there was significant decrease in GSH-Px(P <0.05), but not in SOD(P>0.05).4. There were not significantly difference between the groups of arsenite exposure and the control in gene expression of PNP in different time and dose (P>0.05). The expression of AS3MT was not significantly increase in low arsenite on every time, but in middle and high dose had significantly on every time (P <0.05). The change in GSTO was same too(P <0.05).5. The relative analysis between the oxidative stress and metabolic enzyme: a clear tendency for a positive correlation between MDA and GSTO, AS3MT was found in liver, and the coefficient were 0.510 and 0.443. But the activity of GSH-Px and AS3MT, GSTO were negative correlation, and the coefficient were -0.558 and -0.408. MDA and PNP, GSH-Px and PNP were not correlation, and SOD and PNP, AS3MT, GSTO were also not correlation.Conclusions:1. Low arsenic can induce antioxidatant adaptive increase on mice liver and renal,but eventually induce oxidative stress as the arsenic exposure dose and time increasing.2. Low arsenic can induce expression of AS3MT and GSTO increase, AS3MT and GSTO had a important role in arsenic metabolism and biotransformation.3. There were a clear coefficient oxidative stress and expression of AS3MT and GSTO, there may be relations between oxidative stress and arsenic metabolism.
|
PDF Full Text Request