Comparative effects of chelating agents on pulmonary toxicity of systemic nickel in mice.

ABSTRACT

N-Benzyl-D-glucaminedithiocarbamate (BGD), diethyldithiocarbamate (DDTC), dihydroxyethyldithiocarbamate (DHED), trans-1,2-cyclohexanediamine N,N,N',N'-tetraacetic acid (CDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) were studied for their protective effects against the pulmonary toxicity in mice induced by acute exposure to nickel. Nickel injection increased lipid peroxidation, lactate dehydrogenase (LDH) activity and the concentrations of protein, phospholipids (PL) and essential metals such as Ca, Fe and Zn and decreased the reduced glutathione (GSH) concentration and alkaline phosphatase (ALP) activity in the lungs. At 30 min after Ni treatment, DMSA, BGD and DDTC effectively depressed Ni concentration in the lungs. At 24 h after Ni treatment, DMSA and BGD were effective in mobilizing Ni from the lungs. Both DMSA and BGD significantly prevented increases in lipid peroxidation and in the concentrations of PL, Ca, Fe and Zn, and decreases in GSH concentration and ALP activity in the lungs of mice caused by Ni injection. Treatment with DMSA or BGD was more effective than that with other chelating agents in decreasing the pulmonary Ni concentration and preventing other changes caused by acute exposure to Ni, resulting in effective protection against Ni-induced pulmonary damage.