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Metabolomic effects in HepG2 cells exposed to four TiO2 amd two CeO2 naomaterials
Citation:
Kitchin, K., E. Grulke, B. Robinette, AND B. Castellon. Metabolomic effects in HepG2 cells exposed to four TiO2 amd two CeO2 naomaterials. Environmental Science: Nano. RSC Publishing, Cambridge, Uk, 1:466-477, (2014).
Impact/Purpose:
We found several interesting findings of importance (a) decreases in the antioxidant glutathione system (b) changes in dimethylarginine and iNOS and (c) many lipid changes. There are many cases of different effects being caused by different nanomaterials. Because we found such large differences between chemically similar nanomaterials, this evidence argues against considering nanomaterial as representative of an entire chemical class of nanomaterials (e.g. all CeO2 containing nanoproducts.)
Description:
Abstract It is difficult to evaluate nanomaterials potential toxicity and to make science-based societal choices. To better assess potential hepatotoxicity issues, human liver HepG2 cells were exposed to four Ti02 and two Ce02 nanomaterials at 30 ug m1-1 for three days with dry mean primary particle sizes ranging from 8 to 142 nm. Twonanomaterials were also run at 3 ug ml-1• A metabolomics study was then performed using three mass spectroscopy dependent platforms (LC and GC). Five of the six nanomaterials strongly reduced glutathione concentration. The two strongest effectswere from exposures to a Ti02 (59 nm) and a Ce02 (8 nm), both from NanoAmor. Thedecreases in the GSH system were observed in (a) GSH precursors (glutamate and cysteine), (b) GSH itself and (c) GSH metabolites (the gamma-glutamyl condensation products with glutamate, glutamine, alanine, valine and also 5-oxoproline andcysteine-GSH). The glutathione decreases were the largest decreases seen among the 265 biochemical metabolites determined and is consistent with nanomaterials actingvia an oxidative stress mode of action. Ce02, but not Ti02, increased asymmetricdimethylarginine concentration and thus possible decreases in iNOS activity and NOconcentration could result. One Ce02 (8 nm from NanoAmor) increased concentrationsof many lipids, particularly fatty acids. Similar statistically significant elevations were seen in several other classes of lipids (lysolipid, monoacylglycerol, diacylglycerol and sphingolipid) but not in all classes of lipids (glycerolipid , camitine and fatty acid dicarboxylate). None of the other 5 nanomaterials had this lipid effect. Thus, metabolomic analysis of nanomaterial treated HepG2 cells revealed several previously unknown biochemical effects.