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Gamma-gtp Inhibitor Acivicin Liver, Renal Methylmercury Content Of Experimental Research

Posted on:2004-04-24Degree:MasterType:Thesis
Country:ChinaCandidate:X J CaoFull Text:PDF
GTID:2204360092995993Subject:Health Toxicology
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PrefaceMethyl mercury is an environmental contaminant with neural tox-icity. It comes from waste liquids volleyed by many factories. After absorption into blood, methyl mercury will accumulate in kidney, liver and brain. The excretion of methyl mercury becomes very difficult because of high enterohepatic circulation and reabsorption by proximal convoluted tubule.Many conventional medicines like EDTA can result in metabolic disorders of microelements, even renal toxicity. Find a drug that can accelerate the excretion of methyl mercury particularly is an emergency. Investigations found that the reabsorption of methyl mercury is related with an enzyme, y - Glutamyl transpeptidase(-y - GTP). Tana-ka's research found that large dose of Aeivicin can accelerate the excretion and decrease renal content at the same time.In this study, we investigate whether inhibition of y - GTP activity will facilitate the excretion of methyl mercury and relieve the load in liver and kidney, so this can provide a new way to therapy methyl mercury intoxication.Materials and Methods1. Animal grouping, administration and sample collection 5 days after injection of Methyl mercury chloride (5. 0mg/kg) , 42 adult male mice were randomly assigned into four groups: the ini-tial, 0.0, 0. 3 and 3. 0mg/kg acivicin groups. The latter three groups were injected subcutaneously with saline and acivicin every three days. The mice of initial group were perfused through heart with pre-cooled - saline until the effluent is without any blood. Then collect liver and kidney. Two hours after administration in the 12th day and 45th day, the mice were perfused through heart with precooled - saline until the effluent is without any blood. Then collect liver and kidney.2. Observation and determination2.1 Body weight: measure directly.2.2 -y - GTP activity: -y - Glutamyl - p - nitro - aniline simple chromatometry and protein content with Coomassie brilliant blue chromatometry.2.3 GSH content: DTNB direct chromatometry.2.4 Methyl mercury determination; gas chromatography with e-lectronic capture detector.3. Data statistical analysis; analysis of variance and q - test were performed with SPSS packages.Results1. The effect of different doses of acivicin to mice body weight No significant difference was found between the test groups andcontrol group before and during experimental period of time ( p > 0.05).2. The effect of different doses of acivicin to -y - GTP activity of liver and kidney2 hours after administration in the 12th and 45th day, no signifi-cant differences were observed in liver - GTP activity ( p < 0. 05 ). But the kidney - GTP acitivity of 3. 0mg/kg group is significantly lower than control ( p < 0.05 ).3. The effect of different doses of acivicin to GSH content of liver and kidney2 hours after administration in the 12th day, GSH contents of liver and kidney in acivicin groups are lower than the control (p <0.05) and decreased with the increase of acivicin dose. 2 hours after administration in the 45th day, no significant difference was found between the experimental groups and the control ( p > 0. 05 ) , but the content of GSH will decrease with the increase of acivicin dose.4. The effect of different doses of acivicin to methyl mercury content in liver and kidneyAfter administration in the 12th days, methyl mercury content in liver of 3.0mg/kg group is significantly lower than the control (p <0. 05) , and has dose - effect relationship. After administration in the 45th day, the mice administrated with acivicin have significant lower contents in liver than the control ( p < 0.05 ). After administration in the 12th and 45th day, the contents in kidney of 0. 3 and 3. Omg/kg groups were lower than the control, but not significantly (p >0.05) , and with the time going and dose increasing, the content decreased.DiscussionAfter the Japanese Mminamata Disease in the 1950's, many scientists began to study the metabolism of methyl mercury. They found tha...
Keywords/Search Tags:Acivicin, γ-GTP, GSH, Methyl mercury, male mice
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