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

ObjectiveTo develop a new antidotes for manganese(Mn).MethodsMice were injected intraperitoneally with MnCl₂(100mg MnCl₂/kg).Twenty-four hours after the MnCl₂ 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.ResultsMn 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±0.29μmol/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 MnCl₂ injection.L-His and NAC effectively prevented the increases of the indicators.ConclusionL-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.