Gene expression in liver injury caused by long-term exposure to titanium dioxide nanoparticles in mice

Although liver toxicity induced by titanium dioxide nanoparticles (TiO(2) NPs) has been demonstrated, very little is known about the molecular mechanisms of multiple genes working together underlying this type of liver injury in mice. In this study, we used the whole-genome microarray analysis technique to determine the gene expression profile in the livers of mice exposed to 10 mg/kg body weight TiO(2) NPs for 90 days. The findings showed that long-term exposure to TiO(2) NPs resulted in obvious titanium accumulation in the liver and TiO(2) NP aggregation in hepatocyte nuclei, an inflammatory response, hepatocyte apoptosis, and liver dysfunction. Furthermore, microarray data showed striking changes in the expression of 785 genes related to the immune/inflammatory response, apoptosis, oxidative stress, the metabolic process, response to stress, cell cycle, ion transport, signal transduction, cell proliferation, cytoskeleton, and cell differentiation in TiO(2) NP-exposed livers. In particular, a significant reduction in complement factor D (Cfd) expression following long-term exposure to TiO(2) NPs resulted in autoimmune and inflammatory disease states in mice. Therefore, Cfd may be a potential biomarker of liver toxicity caused by TiO(2) NPs exposure.     

3‐Hydroxyflavone enhances the toxicity of ZnO nanoparticles in vitro

It is recently shown that flavonoids might reduce the toxicity of nanoparticles (NPs) due to their antioxidative properties. In this study, the influence of 3‐hydroxyflavone (H3) on the toxicity of ZnO NPs was investigated. H3 increased hydrodynamic size, polydispersity index and absolute value of the zeta potential of ZnO NPs, which indicated that H3 could influence the colloidal aspects of NPs. Surprisingly, H3 markedly decreased the initial concentration of ZnO NPs required to induce cytotoxicity to Caco‐2, HepG2, THP‐1 and human umbilical vein endothelial cells, which suggested that H3 could promote the toxicity of ZnO NPs to both cancerous and normal cells. For comparison, 6‐hydroxyflavone did not show this effect. H3 remarkably increased cellular Zn elements and intracellular Zn ions in HepG2 cells following ZnO NP exposure, and co‐exposure to H3 and NPs induced a relatively higher intracellular reactive oxygen species. Exposure to ZnO NPs at 3 hours induced the expression of endoplasmic reticulum stress markers DDIT3 and XBP‐1 s, which was suppressed by H3. The expression of apoptotic genes BAX and CASP3 was significantly induced by ZnO NP exposure after 3 and 5 hours, respectively, and H3 further significantly promoted CASP3 expression at 5 hours. In combination, the results from this study suggested that H3 affected colloidal stability of ZnO NPs, promoted the interactions between NPs and cells, and altered the NP‐induced endoplasmic reticulum stress–apoptosis signaling pathway, which finally enhanced the cytotoxicity of ZnO NPs.     

Comparative cytotoxicity of dolomite nanoparticles in human larynx HEp2 and liver HepG2 cells

Dolomite is a natural mineral of great industrial and commercial importance. With the advent of nanotechnology, natural minerals including dolomite in the form of nanoparticles (NPs) are being utilized in various applications to improve the quality of products. However, safety or toxicity information of dolomite NPs is largely lacking. This study evaluated the cytotoxicity of dolomite NPs in two widely used in vitro cell culture models: human airway epithelial (HEp2) and human liver (HepG2) cells. Concentration‐dependent decreased cell viability and damaged cell membrane integrity revealed the cytotoxicity of dolomite NPs. We further observed that dolomite NPs induce oxidative stress in a concentration‐dependent manner, as indicated by depletion of glutathione and induction of reactive oxygen species (ROS) and lipid peroxidation. Quantitative real‐time PCR data demonstrated that the mRNA level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9) were up‐regulated whereas the anti‐apoptotic gene bcl‐2 was down‐regulated in HEp2 and HepG2 cells exposed to dolomite NPs. Moreover, the activity of apoptotic enzymes (caspase‐3 and caspase‐9) was also higher in both kinds of cells treated with dolomite NPs. It is also worth mentioning that HEp2 cells seem to be marginally more susceptible to dolomite NPs exposure than HepG2 cells. Cytotoxicity induced by dolomite NPs was efficiently prevented by N‐acetyl cysteine treatment, which suggests that oxidative stress is primarily responsible for the cytotoxicity of dolomite NPs in both HEp2 and HepG2 cells. Toxicity mechanisms of dolomite NPs warrant further investigations at the in vivo level. Copyright © 2015 John Wiley & Sons, Ltd.     

Hepatic oxidative stress,DNA damage and apoptosis in adult zebrafish following sub‐chronic exposure to BDE‐47 and BDE‐153

Polybrominated diphenyl ethers (PBDEs) are ubiquitous and prolific contaminant in both the abiotic and biotic environment because of the wide industrial applications of these chemicals. In the present study, the effects of 2,2′,4,4′‐tetrabrominateddiphenyl ether (BDE‐47) and 2,2′,4,4′,5,5′‐hexabromodiphenyl ether (BDE‐153) exposure on the induction of hepatic oxidative stress, DNA damage, and the expression of apoptosis‐related genes in adult zebrafish were investigated. The activities of antioxidant enzymes, such as catalase and superoxide dimutase, significantly increased when adult zebrafish was exposed to various concentrations of BDE‐47 and BDE‐153 for 7 and 15 days. BDE‐47 and BDE‐153 elicited significant alterations in zebrafish 7‐Ethoxyresorufin‐O‐deethylase activity at 3, 7, or 15 days of exposure. In addition, the significant increase in comet assay parameters of zebrafish hepatocytes in a concentration‐dependent manner indicated BDE‐47 and BDE‐153 induced DNA damage, probably due to observed oxidative stress. Furthermore, a monotonically upregulation of p53 and Caspase3, which are apoptotic‐regulated genes, and decreased expression ratio of the anti‐apoptotic B‐cell lymphoma/leukaemia‐2 and Bcl2‐associated X protein genes for all BDE‐47 and BDE‐153 treatments at 7 and 15 days indicated apoptosis induction in zebrafish liver. Our findings help elucidate the mechanisms of BDE‐47‐ and BDE‐153‐induced toxicity in zebrafish hepatocytes.     

Accumulation and toxicity of CuO and ZnO nanoparticles through waterborne and dietary exposure of goldfish (Carassius auratus)

Dietary and waterborne exposure to copper oxide (CuO) and zinc oxide (ZnO) nanoparticles (NPs) was conducted using a simplified model of an aquatic food chain consisting of zooplankton (Artemia salina) and goldfish (Carassius auratus) to determine bioaccumulation, toxic effects, and particle transport through trophic levels. Artemia contaminated with NPs were used as food in dietary exposure. Fish were exposed to suspensions of the NPs in waterborne exposure. ICP‐MS analysis showed that accumulation primarily occurred in the intestine, followed by the gills and liver. Dietary uptake was lower, but was found to be a potential pathway for transport of NPs to higher organisms. Waterborne exposure resulted in about a 10‐fold higher accumulation in the intestine. The heart, brain, and muscle tissue had no significant Cu or Zn. However, concentrations in muscle increased with NP concentration, which was ascribed to bioaccumulation of Cu and Zn released from NPs. Free Cu concentration in the medium was always higher than that of Zn, indicating CuO NPs dissolved more readily. ZnO NPs were relatively benign, even in waterborne exposure (p ≥ 0.05). In contrast, CuO NPs were toxic. Malondialdehyde levels in the liver and gills increased substantially (p < 0.05). Despite lower Cu accumulation, the liver exhibited significant oxidative stress, which could be from chronic exposure to Cu ions. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 119–128, 2015.     

Hepatotoxicity and liver injury induced by hydroxyapatite nanoparticles

As hydroxyapatite nanoparticles (HA NPs) are increasingly used in biomedical and biotechnological fields, risk assessment of HA NPs has attracted extensive attention. Nevertheless, little is known about the potential adverse effects of HA NPs on normal hepatocytes and the liver. In the present study, we conducted an in vitro study in which 80‐nm HA NPs were incubated with normal Buffalo rat liver (BRL) cells. By analyzing the changes in cell viability, apoptosis/necrosis and the mitogen‐activated protein kinase (MAPK) signaling pathway, we investigated the cytotoxicity and potential mechanism of HA NPs in hepatocytes. Furthermore, we used the serum hematology and histopathology examinations to explore the in vivo effects of HA NPs on the structure and function of the liver. Our results showed that exposure to HA NPs at a concentration above 200 µg ml^?1 decreased cell viability, increased levels of lactate dehydrogenase (LDH) leakage, induced apoptosis and necrosis, and triggered the MAPK signaling pathway in BRL cells in a dose‐dependent manner. Moreover, our in vivo study indicated that HA NPs increased the white blood cell count (WBC) and the levels of tumor necrosis factor‐α (TNF‐α), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum, caused inflammatory cell infiltration at the portal area in the liver, and induced hepatic oxidative stress with elevated levels of hydrogen peroxide (H₂O₂) and malondialdehyde (MDA). These data demonstrate that at certain concentrations, 80‐nm HA NPs cause hepatotoxicity and liver injury. Copyright © 2014 John Wiley & Sons, Ltd.     

Effects of SiO2 nanoparticles on HFL‐I activating ROS‐mediated apoptosis via p53 pathway

Silicon dioxide nanoparticles (SiO₂ NPs) have attracted increasing interest as nanovehicles for delivering drugs, genes and bio‐active molecules into cells. However, it is still unknown whether SiO₂ NPs could cause side‐effects to normal cells. In the present study, human lung fibroblasts (HFL‐Is) were directly exposed to two different sizes of SiO₂ NPs. The effect of size and concentration on cell response was studied by analyzing the cell viability, the ratio of apoptosis and the pathway of cell injury. The results demonstrated that a size‐associated and a dose‐dependent toxicity of HFL‐Is was induced by SiO₂ NPs. Meanwhile, the expression of reactive oxygen species in HFL‐I was significantly increased. This activation effect was accompanied by upregulation of p53 expression, release of cytochrome C from chondriosomes, inhibition of Bcl2, and activation of Bax and caspase 9. These findings implied that SiO₂ NPs might induce apoptosis of HFL‐Is by stimulating reactive oxygen species release and subsequently causing the activation of p53 pathway in vitro. Copyright © 2011 John Wiley & Sons, Ltd.     

Effects of gold and silver nanoparticles in cultured human osteoarthritic chondrocytes

The aim of our study was to evaluate the effects of gold (Au) and silver (Ag) nanoparticles (NPs) at different concentrations on cultured human osteoarthritic chondrocytes. Cell viability and inducible nitric oxide synthase expression were evaluated by light microscopy. Using transmission electron microscopy (TEM) and field emission gun‐based scanning transmission electron microscopy/energy dispersive spectroscopy (FEG‐STEM/EDS) allowed us to localize NPs. Gene expression of matrix metalloproteinases 1, 3 and 13 and A disintegrin and metalloproteinase with thrombospondin motifs ‐4 and ‐5 were carried out by real‐time polymerase chain reaction. A cell viability test indicated a significant dose‐dependent cytotoxic effect of both NPs. At concentrations of 160 and 250 μM NP light microscopy showed chondrocytes with signs of apoptosis and an increased presence of inducible nitric oxide synthase. Au‐NPs were characterized by FEG‐STEM/EDS and TEM analysis localized NPs in cytoplasm and in endocytotic vesicles. On the contrary, the Ag‐NPs were undetectable by FEG‐STEM/EDS and TEM. Increased gene expression, particularly in matrix metalloproteinase‐3, was observed for both NPs (160 μM), but at a concentration of 250 μM the expression of the evaluated genes became lower. Our in vitro studies, although preliminary, suggest that engineered Au and Ag‐NPs appear to be harmful for human osteoarthritic chondrocytes in high concentrations (160–250 μM). Copyright © 2013 John Wiley & Sons, Ltd.     

Influence of bovine serum albumin pre-incubation on toxicity and ER stress-apoptosis gene expression in THP-1 macrophages exposed to ZnO nanoparticles

When entering a biological environment, proteins could be adsorbed onto nanoparticles (NPs), which can potentially influence the toxicity of NPs. This study used bovine serum albumin (BSA) as the model for serum protein and investigated its interactions with three different types of ZnO NPs, coded as XFI06 (pristine NPs of 20?nm), NM110 (pristine NPs of 100?nm) and NM111 (hydrophobic NPs of 130?nm). Atomic force microscope indicated the adsorption of BSA to ZnO NPs, leading to the increase of NP diameters. Pre-incubation with BSA did not significantly affect hydrodynamic size but decreased Zeta potential of NM110 and NM111. The fluorescence and synchronous fluorescence of BSA were quenched after pre-incubation with ZnO NPs, and the quenching effects were more obvious for XFI06 and NM110. Exposure to all types of ZnO NPs significantly induced cytotoxicity and lysosomal destabilization, which was slightly alleviated when NPs were pre-incubated with BSA. However, ZnO NPs with or without pre-incubation of BSA resulted in comparable intracellular Zn ions, glutathione and reactive oxygen species in THP-1 macrophages. Exposure to ZnO NPs promoted the expression of endoplasmic reticulum (ER) stress markers (DDIT3 and XBP-1s) and apoptosis genes (CASP9 and CASP12). Pre-incubation with BSA had minimal impact on ER stress gene expression but decreased apoptosis gene expression. Combined, these results suggested that pre-incubation with BSA could modestly alleviate the cytotoxicity and reduce ER stress related apoptosis gene expression in THP-1 macrophages after ZnO NP exposure.     

Size dependent toxicity of zinc oxide nano-particles in soil nematode Caenorhabditis elegans

Abstract

Zinc oxide nano-particles (ZnO NPs), with their unique physico-chemical properties conferred by various size formulations, are extensively used in consumer products. The enormous usage coupled with their release to the environment demands risk assessment of ZnO NPs on health and the environment. Toxicity of ZnO NPs is well understood in comparison to the bulk ZnO. However, toxicity in relation to the NP size is poorly understood. In this context, we examined the adverse effects of different sizes (35?nm, 50?nm and 100?nm) of ZnO NPs in soil nematode C. elegans along with bulk ZnO and ZnCl₂. Here, we show that growth, reproduction and behavior of worms were adversely affected by ZnO NPs in a size dependent manner. Further, exposure to ZnO NPs caused modulation of expression/function of genes associated with Insulin/IGF-like signaling pathway and/or stress response pathway in a size dependent manner in exposed worms. The expression of pro-apoptotic gene and suppression of anti-apoptotic genes, together with increased numbers of cell corpses in the germ line, indicated that apoptosis was also dependent on the size of the ZnO NP. Taken together, our study provides evidence that exposure to ZnO NPs disrupts various physiological processes and causes apoptosis in the germ-line even at very low concentration in a size dependent manner. Our finding suggests the inclusion of size as an additional measure for the cautious monitoring of ZnO NP disposal into the environment.     

Artemisinin inhibits tumour necrosis factor‐α‐induced vascular smooth muscle cell proliferation in vitro and attenuates balloon injury‐induced neointima formation in rats

The aim of this study was to evaluate the effect of artemisinin (ART) on rat vascular smooth muscle cell (VSMC) proliferation induced by tumour necrosis factor (TNF)‐α, cell cycle arrest, and apoptosis, and its effect on neointima formation after balloon injury of rat carotid artery. Primary rat VSMC were identified by immunofluorescence assay. The proliferation of VSMC induced by TNF‐α was significantly inhibited by ART treatment in a dose‐dependent manner. Treatment with 100‐μM ART significantly reduced the expression of proliferating cell nuclear antigen. In contrast, the same treatment arrested the cell cycle in G0/G1 phase. Western blot analysis showed that the cell cycle‐related proteins cyclin D1, cyclin E, cyclin‐dependent kinase 2, and cyclin‐dependent kinase 4 were downregulated by ART in TNF‐α‐stimulated VSMC. For apoptosis induced by ART, cleaved caspase‐3/‐9 was detected, and the pro‐apoptotic protein Bcl‐2‐associated X protein was upregulated while the anti‐apoptotic protein Bcl‐2 was downregulated. The results suggest that ART can effectively inhibit the proliferation of VSMC induced by TNF‐α through the apoptotic induction pathway and cell cycle arrest. Also, balloon injury indicated that ART significantly inhibited neointima formation in the rat carotid arteries.     

cDNA microarray analysis of the gene expression of murine leukemia RAW 264.7 cells after exposure to propofol

Propofol (2,6‐diisopropylphenol) is the most extensively used general anesthetic‐sedative agent and it is employed in clinical patients. It has been shown that propofol exhibits anticancer activities. However, there is no available information to address propofol‐induced cytotoxic effects and affected gene expressions on murine leukemia cells. Therefore, we investigated the effects of propofol on the levels of protein and gene expression, which are associated with apoptotic death in mouse leukemia RAW 264.7 cells in vitro. Results indicated that propofol induced cell morphological changes, cytotoxicity, and induction of apoptosis in RAW 264.7 cells in vitro. Western blot analysis demonstrated that propofol promoted Fas, cytochrome c, caspase‐9 and ?3 active form and Bax levels, but inhibited Bcl‐xl protein level which led to cell apoptosis. Furthermore, cDNA microarray assay indicated that propofol significantly enhanced 5 gene expressions (Gm4884; Gm10883; Lce1c; Lrg1; and LOC100045878) and significantly suppressed 26 gene expressions (Gm10679; Zfp617; LOC621831; LOC621831; Gm5929; Snord116; Gm3994; LOC380994; Gm5592; LOC380994; Gm4638; LOC280487; Gm4638; Tex24; A530064D06Rik; BC094916; EG668725; Gm189; Hist2h3c2; Gm8020; Snord115; Gm3079; Olfr198; Tdh; Snord115; and Olfr1249). Based on these observations, propofol‐altered apoptosis‐related proteins might result from induction of apoptotic gene expression and inhibition of cell growth gene expression, which finally led to apoptosis in a mouse leukemia cell line (RAW 264.7) in vitro. © 2011 Wiley Periodicals, Inc. Environ Toxicol 28: 471–478, 2013.     

Casticin induced apoptotic cell death and altered associated gene expression in human colon cancer colo 205 cells

Casticin, a polymethoxyflavone, derived from natural plant Fructus Viticis exhibits biological activities including anti‐cancer characteristics. The anti‐cancer and alter gene expression of casticin on human colon cancer cells and the underlying mechanisms were investigated. Flow cytometric assay was used to measure viable cell, cell cycle and sub‐G1 phase, reactive oxygen species (ROS) and Ca²⁺ productions, level of mitochondria membrane potential (ΔΨ_m) and caspase activity. Western blotting assay was used to detect expression of protein level associated with cell death. Casticin induced cell morphological changes, decreased cell viability and induced G2/M phase arrest in colo 205 cells. Casticin increased ROS production but decreased the levels of ΔΨ_m, and Ca²⁺, increased caspase‐3, ‐8, and ‐9 activities. The cDNA microarray indicated that some of the cell cycle associated genes were down‐regulated such as cyclin‐dependent kinase inhibitor 1A (CDKN1A) (p21, Cip1) and p21 protein (Cdc42/Rac)‐activated kinase 3 (PAK3). TNF receptor‐associated protein 1 (TRAP1), CREB1 (cAMP responsive element binding protein 1) and cyclin‐dependent kinase inhibitor 1B (CDKN1B) (p27, Kip1) genes were increased but matrix metallopeptidase 2 (MMP‐2), toll‐like receptor 4 (TLR4), PRKAR2B (protein kinase, cAMP‐dependent, regulatory, type II, bet), and CaMK4 (calcium/calmodulin‐dependent protein kinase IV) genes were inhibited. Results suggest that casticin induced cell apoptosis via the activation of the caspase‐ and/or mitochondria‐dependent signaling cascade, the accumulation of ROS and altered associated gene expressions in colo 205 human colon cancer cells.     

Cytotoxicity and apoptotic gene expression in an in vitro model of the blood–brain barrier following exposure to poly(butylcyanoacrylate) nanoparticles

Background Poly(butylcyanoacrylate) (PBCA) nanoparticles (NPs) loaded with doxorubicin (DOX) and coated with polysorbate 80 (PS80) have shown efficacy in the treatment of rat glioblastoma. However, cytotoxicity of this treatment remains unclear.

Purpose The purpose of this study was to investigate cytotoxicity and apoptotic gene expression using a proven in vitro co-culture model of the blood–brain barrier.

Methods The co-cultures were exposed to uncoated PBCA NPs, PBCA-PS80 NPs or PBCA-PS80-DOX NPs at varying concentrations and evaluated using a resazurin-based cytotoxicity assay and an 84-gene apoptosis RT-PCR array.

Results The cytotoxicity assays showed PBCA-PS80-DOX NPs exhibited a decrease in metabolic function at lower concentrations than uncoated PBCA NPs and PBCA-PS80 NPs. The apoptosis arrays showed differential expression of 18 genes in PBCA-PS80-DOX treated cells compared to the untreated control.

Discussion As expected, the cytotoxicity assays demonstrated enhanced dose-dependent toxicity in the DOX loaded NPs. The differentially expressed apoptotic genes participate in both the tumor necrosis factor receptor-1 and mitochondria-associated apoptotic pathways implicated in current DOX chemotherapeutic toxicity.

Conclusion The following data suggest that the cytotoxic effect may be attributed to DOX and not the NPs themselves, further supporting the use of PBCA-PS80 NPs as an effective drug delivery vehicle for treating central nervous system conditions.     

Evaluation of the toxicity of food additive silica nanoparticles on gastrointestinal cells

Silica nanoparticles (NPs) have been widely used in food products as an additive; however, their toxicity and safety to the human body and the environment still remain unclear. As a food additive, silica NPs firstly enter the human gastrointestinal tract along with food, thus their gastrointestinal toxicity deserves thorough study. Herein, we evaluated the toxicity of food additive silica NPs to cells originating from the gastrointestinal tract. Four silica NP samples were introduced to human gastric epithelial cell GES‐1 and colorectal adenocarcinoma cell Caco‐2 to investigate the effect of silica sample, exposure dose and exposure period on the morphology, viability and membrane integrity of cells. The cell uptake, cellular reactive oxygen species (ROS) level, cell cycle and apoptosis were determined to reveal the toxicity mechanism. The results indicate that all four silica NPs are safe for both GES‐1 and Caco‐2 cells after 24‐h exposure at a concentration lower than 100 µg ml^–1. At a higher concentration and longer exposure period, silica NPs do not induce the apoptosis/necrosis of cells, but arrest cell cycle and inhibit the cell growth. Notably, silica NPs do not pass through the Caco‐2 cell monolayer after 4‐h contact, indicating the low potential of silica NPs to cross the gastrointestinal tract in vivo. Our findings indicate that silica NPs could be used as a safe food additive, but more investigations, such as long‐term in vivo exposure, are necessary in future studies. Copyright © 2013 John Wiley & Sons, Ltd.     

Mechanisms underlying melatonin-mediated prevention of fenvalerate-induced behavioral and oxidative toxicity in zebrafish

The neurotoxic effects attributed to the pesticide fenvalerate (FEN) are well-established. The aim of this study was to determine whether melatonin (MLT) was able to protect against FEN-induced behavior, oxidative stress, apoptosis, and neurogenesis using zebrafish (Danio rerio) model. Zebrafish exposed to 100 μg/L FEN for 120 h exhibited decreased swimming activity accompanied by downregulated expression of neurogenesis-related genes (Dlx2, Shha, Ngn1, Elavl3, and Gfap), suggesting that neurogenesis were impaired. In addition, FEN exposure significantly elevated oxidative stress as evidenced by increased malondialdehyde levels, as well as activities of Cu/Zn superoxide dismutase (Cu/Zn SOD), catalase, and glutathione peroxidase. Acridine orange staining demonstrated that embryos treated with FEN for 120 h significantly enhanced apoptosis mainly in the brain. FEN also produced upregulation of the expression of the pro-apoptotic genes (Bax, Fas, caspase 8, caspase 9, and caspase 3) and decreased expression of the anti-apoptotic gene Bcl-2. MLT significantly attenuated the FEN-mediated oxidative stress, modulated apoptotic-regulating genes, and diminished apoptotic responses. Further, MLT blocked the FEN-induced effects on swimming behavior as well as on neurogenesis-related genes. In conclusion, MLT protected against FEN-induced developmental neurotoxicity and apoptosis by inhibiting pesticide-mediated oxidative stress in zebrafish.     

MicroRNA expression changes during zebrafish development induced by perfluorooctane sulfonate

Perfluorooctane sulfonate (PFOS), a kind of widely distributed environmentally organic compound, has been found to cause developmental toxicity. Although microRNAs (miRNAs) play an important role in many metabolic tasks, whether and how they are involved in the process of PFOS‐induced toxicity is largely unknown. To address this problem, PFOS‐induced changes in miRNAs and target gene expression in zebrafish embryos, and the potential mechanism of PFOS‐induced toxic action were studied in this research. Zebrafish embryos were exposed to 1 µg ml^?1 PFOS or DMSO control from 6 h post‐fertilization (hpf) to 24 or 120 hpf. Subsequently, RNA was isolated from the embryo pool and the expression profiles of 219 known zebrafish miRNAs were analyzed using microarray. Finally, quantitative real‐time polymerase chain reaction was used to validate several miRNAs expression of microarray data. The analysis revealed that PFOS exposure induced significant changes in miRNA expression profiles. A total of 39 and 81 miRNAs showed significantly altered expression patterns after PFOS exposure 24 and 120 hpf. Of the changed miRNAs, 20 were significantly up‐regulated and 19 were significantly down‐regulated (p < 0.01) at 24 hpf, whereas 41 were significantly up‐regulated and 40 were significantly down‐regulated (p < 0.01) at 120 hpf. These miRNAs were involved in development, apoptosis and cell signal pathway, cell cycle progression and proliferation, oncogenesis, adipose metabolism and hormone secretion, whereas there is still little functional information available for 32 miRNAs. Our results demonstrate that PFOS exposure alters the expression of a suite of miRNAs and may induce developmental toxicity. Copyright © 2010 John Wiley & Sons, Ltd.