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Effects Of Low Doses Of Arsenic On Liver And Hepatic Proteins In Animals

Posted on:2011-08-03Degree:MasterType:Thesis
Country:ChinaCandidate:X J FanFull Text:PDF
GTID:2154360305478923Subject:Health Toxicology
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Objective1.To observe the influence of lower arsenic on some of the serum biochemical indexes in rabbit.2.To use two-dimensional gel electrophoresis to analyse the difference of protein expression of between the rats induced by low doses of arsenic and the normal rats were investigated on the molecular pathways of the early biomarker, furthermore, work out their detailed mechanism of the development of arsenic poisoning.Methods1.12 rabbits were randomly divided in to four groups. Rabbits were treated with arsenic concentration of 0μg/L, 10μg/L,50μg/L,250μg/L in drinking water. The indexes ALT, AST, r-GT, ALP, TP, ALB, GLP, ALB/GLP were measured after 8 weeks and 12 weeks exposure. Pathohistology analysis of the liver was also performed. The effects of arsenic on the contents of malondialdehyde (MDA) and the activities of superoxide dismutase(SOD) were observed. The total arsenic of liver and bile were determined by atomic fluorescence spectrometry (AFS).2.48 rats were randomly divided into four groups, each of which was treated with arsenic at 0μg/L,50μg/L,150μg/L, and 450μg/L in drinking water. After 4 week's exposure the rats were killed and the livers were collceted. The general toxicicities (bodyweight, water consumption, and main organ/body) were observed. The total arsenic of blood and liver were determined by atomic fluorescence spectrometry (AFS). This experientment is designed to research the proteomic differences among the rats induced by low doses of arsenic and the normal rats by two-dimensional gel electrophore-sis (2-DE) and mass spectrometr.Results1. The result showed that the rabbit body weight increased with the dose and the low dose increased significantly.2.The results showed that AST in 250μg/L of 8 weeks increased significantly compared with the contemporary controls (P<0.05). ALT, ALP,γ-GT in 50μg/L of 12 weeks increased significantly (P<0.05). AST, ALP in 250μg/L of 12 week increased significantly (P<0.05).3. The results showed that protein in blood serum were no significantly change.4. MDA levels of liver in high dose group was significantly higher than that in controls but the activities of SOD in high-dose group was significantly lower than that in controls.5. The total arsenic in liver and bile were gradually increase with the time,the bile arensic in 250μg/L increased signficially (P< 0.05)6. The pathohistology examination result showed that there are no heapto cellar necrosis and infiltration of the inflammation cells by the light microscopy There is congestions in central veins in the low dose group. In the middle dose, there are not only the expansions and congestions of the vascular, but also the liver cells border is unclear, and they are disorder. In the high dose group the liver cells with cental venous disappeared.Instead of the apparent proliferation of fibroblasts and a lot of collagen Remnant liver cells were a slight disorder, a slight expansion of hepatic sinusoid.7 Liver, renal and heart index increases significantly in 50μg/L compared with the control (P<0.05).Liver index increases significantly in 150μg/L compared with the control(P<0.05)8. The total arsenic in blood and liver gradually increased with the increasement of the dose, there were significant increases in high dose compared with the control (P<0.05). Therefore, the accumulation of arsenic was mainly in liver.9.2-DE result9.1 Compared with the control, there were none expression of thirty-one protein pots, upexpressoon of one protein pots, and down expression of eleven protein pots in 50μg/L group9.2 Compared with the control, there were none expression of twenty-three protein pots and down expression of fifteen protein pots in 150μg/L group.9.3 Compared with the control, expression of eight protein pots decrease and one proteins pots increase in 450μg/L group.Conclusions1. Results related liver injury showed that there were no significantly effect in 10μg/L.2.50μg/L and over 50μg/L arsenic exposure can obviously injury the liver cell. Compared with the other serum enzyme, AST in serum enzyme is more sensitive in earlier injury of the arsenic poisoning. Rabbit liver pathology showed that 50μg/L and over 50μg/L arsenic exposure were on significantly effect on liver cell.3. Rabbit liver were injuried by lipid peroxidation, and with the dose increased the injury more serious.4. The total arsenic in rabbit body showed that arsenic were metabolism in liver, then to excrete in bile. The total arsenic in rat body showed that with the arsenic dose increase, the accumulation of arsenic was mainly in liver and blood.5. Liver, heart and renal were injuried in in 50μg/L, but others were no obviously change.6. The well-resolved and reproducible 2-DE serum pattern of low lever arsenic was established and some differently expressed proteins characterized. There were more protein pots disappearance and decrease in 50μg/L and in 150μg/L.Tthere were 4301,4303,4904,4905,5505,6003,8001,8103,8302,8303,8404,8703,9001,9201,9301,0003,1601, 3603,4202,7403,7501,7603,0603,7203。Among the repetition protein pots is in alkalinity and relate with liver injury.
Keywords/Search Tags:arsenic poisoning, low doses of arsenic, two-dimensional gel electrophoresis, liver damage
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