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Study on Subchronic Arsenic Exposure on Glu and NO Metabolism in Mice

Author: QuChunQing
Tutor: JinYaPing
School: China Medical University
Course: Occupational and Environmental Health
Keywords: Arsenic Glutamine synthetase Phosphate activated glutaminase Glutamate Nitric oxide synthase Nitric oxide
CLC: R599
Type: Master's thesis
Year: 2008
Downloads: 128
Quote: 2
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Abstract

IntroductionEndemic arsenic poisoning is one of major endemic diseases in our country. It has been believed that there has 300 million persons exposed to high-level arsenic, and our country has become one of the most severe countries which are under the danger of arsenic poisoning in the world. In recent years, It has been paid close attention to toxic effects of arsenic on central nervous system. Clinical research, epidemiological investigation and animal experiment all explore that exposed to arsenic can result in abnormal behavior and intellectual disturbance of experimental objects for a long time.Materials and Methods1. Animals and treatmentSelect female and healthy mice, whose weights are between 14-16g. After adaptive environment, the animals were randomly divided into 4 groups of 8 animals each and were allowed ad libitum drinking water containing 25,50, 100mg arsenic/L or untreated drinking water(control group). Exposure was continuous for 42 days. After etherization, blood samples were taken from eyeballs and brains were extracted immediately , stored at -40℃.2. Methods(1) The concentrations of different species of As in blood and brain: hydride generation- cold iron capture-atomic absorption spectrophotometry.(2) The activities of glutamine synthetase: the formation ofγ-glutamyl hydroxamate by the absorbance of the solution at 535nm.(3) The activities of phosphate activated glutaminase: Curthoys and Lowry method.(4) The concentrations of glutamate: kits produced by Nanjing jiancheng. (5) The activities of nitric oxide synthase: kits produced by Nanjing jiancheng.(6) The concentrations of nitric oxide: kits produced by Nanjing jiancheng.(7) The concentrations of proteins: biuret method.3. StatisticsThe data were input into computers, analyzed and treated by the SPSS 13.0. The concentrations of different species of As in blood and brain did not show the normal distribution, so using the Kruskal-Wallis test. Other index were analyzed by analysis of variance(ANOVA).ResultsContents of iAs, MMA and DMA in bloods and brains increased along with the iAs~Ⅲconcentrations in drinking water. The activities of GS, PAG and concentrations of Glu in exposed mice all increased compared with control, and the activities of GS in 50mg/L exposed mice, PAG in 25mg/L and 50mg/L, the concentrations of Glu in 100mg/L exposed mice had significant differences compared with control, and the activities of PAG in 25mg/L were higher significantly than in group of 100mg/L. The activities of NOS and the concentrations of NO in exposed mice all decreased compared with control, and the concentrations of NO in 100mg/L exposed mice had significant differences compared with control, 25mg/L and 50mg/L. The activities of iNOS in every arsenic-exposed groups were lower significantly than control, and the activity in 100mg/L had significant differences compared with 50mg/L group. The activities of iNOS in every arsenic-exposed groups were lower significantly than control. The activities of cNOS in 100mg/L-exposed group had significant differences compared with control and 50mg/L.Conclusions1. Under certain doses, inorganic arsenic and arsenicals can enter into the brain from blood through the brain-blood barrier of mice. DMA was much easier to enter into the brain compared with iAs.2. Subchronic arsenic exposure can strengthen the activities of glutamine synthase and phosphate activated glutaminase, interfere the normal metabolism of glutamate, and lead to damage of functions of central nervous system including learning and memory. 3. Subchronic arsenic exposure can attenuate the activities of nitric oxide synthase, decrease the concentration of nitric oxide, and lead to damage of functions of central nervous system including learning and memory.

Study on Subchronic Arsenic Exposure on Glu and NO Metabolism in Mice

Abstract

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