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 evaluated were cell proliferation by quantification of total protein content, cytoplasmic membrane integrity to cytosolic lactate dehydrogenase leakage, and lysosomal hexosaminidase release. Metabolic markers were lactate dehydrogenase activity and mitochondrial succinate dehydrogenase activity. Lysosomal markers were relative neutral red uptake by lysosomes, and lysosomal hexosaminidase sphingolipid degradation activity. Acetylcholinesterase activity on intact cells was also quantified. Nickel was found to be 36 times more toxic than lithium to neuroblastoma cell proliferation (EC(50)= 0.29 and 10.5 mM, respectively), but the relative extent of other alterations differed. Lithium stimulated nearly all the indicators studied, particularly lactate dehydrogenase, mitochondrial succinate dehydrogenase and acetylcholinesterase activities, as well as hexosaminidase release. In contrast, nickel mainly stimulated hexosaminidase release and inhibited lactate dehydrogenase activity. The stabilization of the cytoplasmic membrane to lactate dehydrogenase leakage simultaneously with the secretion of lysosomal hexosaminidase for both compounds also shows that functional metabolic alterations produced by lithium and nickel are more important than cytoplasmic damage.
Repetto
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National Institute of Toxicology, PO Box 863, 41080 Seville, Spain. repetto@inaltox.es
del Peso
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Sanz
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Repetto
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D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008094:Lithium / Q000633:toxicity*; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009499:Neutral Red / Q000378:metabolism; D009532:Nickel / Q000633:toxicity*; D013107:Sphingolipids / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D015415:Biomarkers; D013107:Sphingolipids; D009499:Neutral Red; D009532:Nickel; D008094:Lithium; D007770:L-Lactate Dehydrogenase; D013385:Succinate Dehydrogenase; D000110:Acetylcholinesterase; D001619:beta-N-Acetylhexosaminidases