4种形态砷在大鼠体内的药物动力学及亚急性毒性比较研究

Comparison of pharmacokinetics and subacute toxicity for four arsenic species in rats

目的 4种形态的砷(As)在大鼠中的吸收、分布、转化、排泄及毒性的初步比较研究。方法通过采用81只大鼠对砷的4种形态28 d动物代谢试验,获得大鼠排泄物(粪和尿)、血液、7个身体部位的4种砷含量数据4 050个,以及28 d给药后的肝脏和肾脏的病理分析,比较研究了砷酸盐[As(Ⅴ)]、亚砷酸盐[As(Ⅲ)]、一甲基砷酸(MMAV)和二甲基砷酸(DMAV)在大鼠中的分布、代谢及亚急性毒性效应。结果大鼠分别给药4种形态的砷后,分别有82.9%的As(Ⅲ)、85.1%的As(Ⅴ)、95.0%的MMAV和96.2%的DMAV通过粪便和尿液排出,16.2%的As(Ⅲ)、14.1%的As(V)、4.65%的MMAV和0.120%的DMAV保留在血液中。随着As(Ⅲ)、As(Ⅴ)和MMAV给药时间的延长,DMAV在血液和尿液中积累,血液中的含量比尿液中高8倍。4种形态的砷对大鼠肝功能、肾功能均有一定影响,对肝功能的影响为急性期效应,对肾功能的影响主要表现为累积效应,As(Ⅲ)的影响最明显,其次为MMAV。4种形态的砷均会引起组织细胞变形,炎性细胞浸润,但未表现出组间差异。结论 4种形态的砷在大鼠体内的分布、代谢、排泄和肝肾毒性方面均存在不同程度的差异,对砷的健康风险应针对不同形态分开研究。

Objective Study on the absorption,distribution,transformation,excretion and toxicity of four forms of arsenic in rats. Methods Four thousand and fifty data were obtained from 28 days animal metabolism experiments of 81 rats exposed to the four As species. Distribution,metabolism,excretion,and subacute toxicity of 4 As species were compared by analyzing the arsenate [As（ Ⅴ） ],arsenite [As（ Ⅲ） ],methyl arsenate（ MMAV） and dimethyl arsenate（ DMAV） content of rat feces（ excrement and urine）,blood,seven organs,and liver and kidney pathology. Results After oral administration of each As species,82. 9% of As（ Ⅲ）,85. 1% of As（ Ⅴ）,95. 0% of MMAV and 96. 2% of DMAV were accumulatively secreted via feces and urine,while 16. 2% of As（ Ⅲ）,14. 1% of As（ Ⅴ）,4. 65% of MMAV and 0. 120% of DMAV were detected in blood. The DMAV accumulated in blood and urine after dosing As（ Ⅲ）,As（ Ⅴ）and MMAV,and the content of DMAV in the blood was 8 times greater than urine. Four kinds of arsenic had effects on rat liver and kidney function,the influence on liver was acute phase effect while that on renal was cumulative effects. Theeffect of As（ Ⅲ） was the most significant,followed by MMAV. Four kinds of arsenic could cause tissue deformation and inflammatory cells infiltration,but showed no difference between groups. Conclusion The distribution,metabolism,excretion,and toxicity of the four kinds of arsenic in rats were different in varying degrees. The research of health risk for arsenic should consider its different forms.