不同螯合剂对锰致小鼠肝脏毒性解毒效果评价

Effects of chelating agents on liver toxicity induced by acute manganese exposure in mice

目的研发高效的锰中毒解毒剂。方法小鼠一次性腹腔注射MnCl2(100 mg/kg),24 h后分别给予L-组氨酸(L-His)、乙二胺四乙酸(EDTA)、二乙基二硫代氨基甲酸钠(DDTC)、meso-2,3-二巯基丁二酸(DMSA)及N-乙酰-L-半胱氨酸(NAC)等五种螯合剂(2 mmol/kg,腹腔注射),观察小鼠血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)和乳酸脱氢酶(LDH)活性、肝脏脂质过氧化物值(LPO)和肝脏组织中锰、钙、锌浓度变化。结果染锰2 d后小鼠血清AST、ALT和LDH活性分别达(251.00±74.28)、(141.00±21.04)、(1393.51±202.01)U/L,肝脏中LPO值为(2.88±0.29)μmol/g prot,锰浓度(18.34±4.74)μg/g,明显高于对照组,差异有统计学意义(P<0.05),L-His和NAC对染锰引起的血清LDH、AST、ALT活性及肝LPO和锰含量升高有明显抑制作用。结论 L-His和NAC对锰致小鼠肝脏毒性有较好解毒作用,有望成为理想的锰解毒剂。

Objective To develop a new antidotes for manganese（Mn）. Methods Mice were injected intraperitoneally with MnC12 （100mg MnC12/kg）. Twenty-four hours after the MnC12 treatment, the mice were injected intraperitoneally with one of the five chelating agents （ 2 mmol/kg for each ）, such as L-histidine （ L-His ）, ethylene diaminetetraacetic acid （ EDTA）, diethyldithiocarbamate （ DDTC ）, meso-2,3-dimercapto succinc acid （ DMSA ） , and N-acetylcysteine （ NAC ）, respectively. The effects of the chelating agents on activities of lacatate dehydrogenase （ LDH）, aspartate transcarbamoylase （AST） and alanine aminotranferase （ALT） in serum, lipid peroxidation （LPO） , and concentrations of Mn, Ca, Zn in liver of the mice induced by the acute manganese exposure were studied. Results Mn injection significantly increased the activities of AST（251.00 ± 74. 28）,ALT（141.00 ± 21.04）, and LDH（1393.51 ±202.01IU/L） in serum, and LPO level （2. 88 ±0. 29 μmol/g prot） ,as well as the concentrations of Mn（ 18.34±4. 74 g/g wet tissue） in the liver of the mice （ P 〈 0. 05 ） two days after the MnC12 injection. L-His and NAC effectively prevented the increases of the indicators. Conclusion L-His and NAC are effective detoxification for the liver toxicity induced by acute Mn exposure in the mice and could be used as antidotes of manganismus.