ABSTRACT
OBJECTIVE To study the toxicity of zinc oxide nanoparticles (ZnO-NPs) on murine macrophage Ana-1 cells and the mechanism.METHODS Ana-1 cells were incubated with ZnO-NP (2.5-160 mg· L-1).Cell viability was investigated by MTT assay.The integrity of cell membrane was investigated by acridine orange-ethidium bromide (AO-EB) staining.The intracellular uptake of ZnO-NP and the percentage of sub-G1 of Ana-1 cells were detected by flow cytometry.Zinc ions were determined by fluorescent probe.The change of cell viability was studied after chelating zinc ions with ethylene diamine tetraacetic acid (EDTA).RESULTS ZnO-NP 2.5,5,10 and 20 mg· L-1 decreased cell viability of Ana-1 cells (r=0.905,P＜0.05) in a concentration-dependent manner.The cell viability was decreased to 27.9％ after exposure to ZnO-NP 20 mg· L-1.Intracellular uptake of ZnO-NP was increased after Ana-1 cell incubated with ZnO-NP at concentrations ranging from 40 to 160 mg· L-1 (P＜0.05).There were obvious free zinc ions in the cells.EDTA 2.5 mmol· L-1 significantly increased the cell viability decreased by ZnO-NP 20 mg· L-1 (P＜0.05).Chelating free zinc ions significantly mitigated ZnO-NP induced cell toxicity (P＜0.05).CONCLUSION Cytotoxicity and apoptosis of Ana-1 cells induced by ZnO-NP might be related to intracellular uptake of ZnO-NP and release of zinc ions.
ABSTRACT
Peroxisome proliferator-activated receptors (PPARs)are ligand-activated nuclear tran-scription factors,playing an important role in the regulation of glucose and lipids metabolism,inflamma-tion response,proliferation and differentiation.Some drugs targeted on PPARs,such as lipid-lowering and antidiabetic drugs have been developed.Some PPAR agonists were found carcinogenic in animal experi ments,including PPAR αagonist fibrates,PPARγagonist thiazolidinediones,PPARα/γdual ago-nist compounds,and PPARδagonist compounds for clinical development.PPARαagonist carcinogenicity is associated with PPAR receptor activation that regulates lipid metabolis m,and leads to lipids abnormali-ties and increase by peroxisome oxidase in reactive oxygen species (ROS),causing DNA damage. Kupffer cells can generate ROS by NAD PH oxidase that pro motes hepatocyte proliferation and inhibition of apoptosis.PPARγagonist carcinogenicity is generally caused by bladder stone.The carcinogenicity of PPAR agonists to humans has not been confirmed,but the carcinogenic potential of these drugs can-not be ignored.