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Study On Mercury Species And Toxic Mechanism In Rats Exposed To Low Level Of Mercury

Posted on:2008-12-21Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:2144360212496416Subject:Drug analysis
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Methylmercury has a irreversible poison affecting nervous system. Methylmercury can easily cross the pacenta and highly accumulate in fatal. The dose of methylmercury that has no effect on pregnant mother can have neurodevelopmental effects including deficits in language, leaning, attention, and a lesser degree fine motor. It has been the hot point in the field of mercury toxicology to investigate the adverse effects on fetus after low-level mercury early in utero exposure. In the present paper, methylmercury and inorganic mercury in brain, liver, kidney subcellular distribution of the dam and pup rats after low-level methylmercury in utero and lactation exposure were determined, and researched a better method of studing metallothionein ,although studed on mechanism of methylmercury's oxidative stress effect, by means of the techniques of HPLC-ICP-MS, SDS-PAGE and the kit relative to oxidative stress etc .The result of methylmercury and inorganic mercury in brain, liver, kidney subcellular distribution of the dam and pup rats indicates that the distribution of methylmercury and inorganic mercury in vivo of the dam and pup rats'cell is essentially different. In the brain of the dam rats, only a little of the methylmercury in the cytosol is converted into inorganic mercury and the rest has not when it comes into the brain. In the brain of the pup rats, inorganic mercury can be determined in every subcellular composition. This result indicates that the metabolism of the methylmercury in the brain of the dam and pup rats is very different, and the brain of pup rats is more sensitive to the toxic effect of methylmercury. In the brain of the dam and pup rats, methylmercury is mainly distributed in the nucleus and than the cytosol, mitochondria and synaptosome.In the liver of the dam rats, the concentration of methylmercury and inorganic mercury in dry weight is very high. The concentration of the inorganic mercury is higer than the methylmercury in lysosome and microsome, this is different from other sucellular compositions. This may indicates that the lysosome is the metabolic place of methylmercury. In the liver of the dam rats, methylmercury mainly distributes in the cytosol, and in the nucleus is less than in the mitochondria, lysosome and microsome. In the liver of the pup rats, methylmercury is mainly distributed in the cytosol and mitochondria, the percentage of methylmercury in the mitochondria is higher than that in the mitochondria of the dam rats'liver. In the liver of the pup rats, 52% of the inorganic mercury is in the cytosol and only 11% is in the nucleus. However, in the liver of the dam rats, the distribution of the inorganic mercury is equal in the subcellular composition.In the kidney of the dam rats, the concentration of methylmercury and inorganic mercury in dry weight is nearly the same in nucleus, mitochondria, lysosome and microsome. The concentration of methylmercury in the cytosol is 2-3 times higher than it in the other subcellular compositions, however the concentration of methylmercury in the cytosol is only 2/3times of the other subcellular compositions. In the kidney of the pup rats, the concentration of inorganic mercury is similar to the distribution of methylmercury, this is very different from the concentration of inorganic mercury in dam rats'kidney. Kidney is the place where the distribution of methylmercury is absolutely the same in the dam rats and the pup rats. In the kidney, 2/3 of the methlymercury is distributed into the cytosol, and only 6% in the nucleus, also less in the mitochondria, lysosome and microsome. In the kidney of the dam rats, inorganic mercury is mainly distributed in the cytosol and mitochondria, and less in nucleus and lysosome etc. In the kidney of the pup rats, the distribution of inorganic mercury is similar to that of methylmercury. This may be caused by unsound excretory system of the pup rats.In the research of the metallothioneins, biological sample was analysed by means of HPLC-ICP-MS,the isoforms of the metallothioneins were separated and this caused the peaks of the metallothioneins very complicated. So we collect the fraction separated with the HPLC at the same condition to have the SDS-PAGE analysis. After try many methods, we find a relatively easy and sensitive method to raise detectability of electrophoresis.On the study on oxidative stress, the lipid peroxidation which caused by methylmercury is serious in the brain of the dam and pup rats, especially in the dam rats in which the content of the MDA is two times higher than the control group. The level of the lipid peroxidation is similar in the dam and pup rats'liver and kidney, and also the lipid peroxidation in liver is more serious than in kidney. In the kidney of the dam rats, the activity of CuZn-SOD and GSH-PX has rised. The activity of CuZn-SOD in the liver and GSH-PX in the brain of the pup rats has rised. This result indicates that the CuZn-SOD and GSH-PX are induced at the transcription level in all this tissues of the dam and pup rats in order to protect themselves. We can see that the mechanism in the pup rats to protect themselves is not as perfect as the one in the dam rats.
Keywords/Search Tags:methylmercury, inorganic mercury, subcellular, metallothionein, lipid peroxidation
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