Size dependent effect of ZnO nanoparticles on endoplasmic reticulum stress signaling pathway in murine liver

ZnO nanoparticles (NPs) have been assessed to show adverse effects on the liver, but the molecular mechanisms and the role of nanoparticle properties in these adverse reactions have not been sufficiently studied. In this study, the toxicity of various sizes of ZnO particles (bulk, 90nm, and 30nm) that were ingested orally over a period of 3days were evaluated in mice. The blood biochemistry, hematological analyses, and histopathological evaluation showed that there was apparent toxicity caused by smaller ZnO NPs (30nm) in liver. The smallest ZnO NPs showed highest accumulation in the mice liver. The RT-qPCR data indicated that 30nm ZnO NPs can induce significant endoplasmic reticulum (ER) stress responses. The ER stress marker of PERK, eIF2α, ATF4, Chop, JNK, caspase-12, caspase-9, GRP94, and Bax at the mRNA levels were higher expression in 30nm ZnO NP than that in bulk or 90nm ZnO. These findings implied that the smaller ZnO NPs (30nm) activated ER stress responses that signified severe apoptosis in murine liver.