In vitro effects of lithium and nickel at different levels on Neuro-2a mouse Neuroblastoma cells

Lithium and nickel present low toxicity, but are able to cause alterations in different tissues. The toxic effects of lithium and nickel at different cellular levels were assessed using two inorganic chemical species: lithium chloride and nickel(II) chloride. Mouse neuroblastoma cell cultures (Neuro -2a) were exposed to both compounds for 24 h. The cytotoxic effects evaluat ed were cell proliferation by quantification of total protein content, cyto plasmic membrane integrity to cytosolic lactate dehydrogenase leakage, and lysosomal hexosaminidase release. Metabolic markers were lactate dehydrogen ase activity and mitochondrial succinate dehydrogenase activity. Lysosomal markers were relative neutral red uptake by lysosomes, and lysosomal hexosa minidase sphingolipid degradation activity. Acetylcholinesterase activity o n intact cells was also quantified. Nickel was found to be 36 times more to xic than lithium to neuroblastoma cell proliferation (EC50 = 0.29 and 10.5 mM, respectively), but the relative extent of other alterations differed. L ithium stimulated nearly all the indicators studied, particularly lactate d ehydrogenase, mitochondrial succinate dehydrogenase and acetylcholinesteras e activities, as well as hexosaminidase release. In contrast, nickel mainly stimulated hexosaminidase release and inhibited lactate dehydrogenase acti vity. The stabilization of the cytoplasmic membrane to lactate dehydrogenas e leakage simultaneously with the secretion of lysosomal hexosaminidase for both compounds also shows that functional metabolic alterations produced b y lithium and nickel are more important than cytoplasmic damage. (C) 2001 P ublished by Elsevier Science Ltd.