Enantioselective apoptosis and oxidative damage induced by individual isomers of profenofos in primary hippocampal neurons

The purpose of this study was to investigate the apoptosis-related cytotoxic effects and molecular mechanisms of individual isomers of profenofos (PFF) on primary hippocampal neurons at 1.0 to 20 mg L^?1. The cell viability and lactate dehydrogenase (LDH) efflux indicated that (?)­PFF exposure was associated with more toxic effects than (+)­PFF above the concentration of 5 mg L^?1 (P < 0.5). Flow cytometric results showed that the percentages of apoptotic cells incubated with 20 mg L^?1 (?)­PFF, (+)­PFF and rac-PFF for 24 h reached 23.4%, 9.2% and 14.2% (P < 0.01), respectively. Hippocampal neurons incubated with (?)­PFF, (+)­PFF and rac-PFF exhibited a dose-dependent accumulation of intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) and a dose-dependent inhibition of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activity, implying that the defense system of the tests induces oxidative damage. A statistically significant difference was observed between the two enantiomers at 5 mg L^?1 and above. Moreover, the results showed that (?)­PFF exposure caused a significant loss in mitochondrial transmembrane potential (MMP), an upregulation of Ca²⁺ and Bax protein expression, a downregulation of Bcl-2 protein expression, and the activation of caspase-3 and caspase-9 in a dose-dependent manner; (+)­PFF and rac-PFF exhibited these effects to a lesser degree. All results suggest that PFF induced apoptosis in rat hippocampal neurons via the mitochondria-mediated pathway, and oxidative stress is one of the factors of PFF-induced apoptosis. In addition, (?)­PFF appears to play an important role in oxidative stress and apoptosis, indicating that enantioselectivity should be considered when assessing ecotoxicological effects and health risks of chiral pesticides.     

Investigation of the effects of static magnetic field on apoptosis in bone marrow stem cells of rat

This research was carried out to evaluate the influence of static magnetic field on the rate of apoptosis in bone marrow stem cells (BMSCs) of rats. Extracted cells were suspended in αMEM as a culture media for 48 h. After that, cells were exposed to 15 mT static magnetic field (SMF) for 5 h, incessantly with or without FeCl₂. The rate of apoptosis was then assessed via flow cytometery. The results showed that either treatment with FeCl₂ or exposure to SMF enhanced the rate of apoptotic cells. Moreover, cells that were treated simultaneously with FeCl₂ and SMF have higher rate of apoptosis. An increase in apoptosis by 26.5% was induced by SMF alone and an increase in apoptosis by 28.2% was induced by a combination of FeCl₂ and SMF, compared to their corresponding controls. The results recommended that the effects of SMF on apoptosis may be related to increment of the number of free radicals in the cells.     

Alterations to proteome and tissue recovery responses in fish liver caused by a short-term combination treatment with cadmium and benzo[a]pyrene

The livers of soles (Solea senegalensis) injected with subacute doses of cadmium (Cd), benzo[a]pyrene (B[a]P), or their combination, were screened for alterations to cytosolic protein expression patterns, complemented by cytological and histological analyses. Cadmium and B[a]P, but not combined, induced hepatocyte apoptosis and Kupfer cell hyperplasia. Proteomics, however, suggested that apoptosis was triggered through distinct pathways. Cadmium and B[a]P caused upregulation of different anti-oxidative enzymes (peroxiredoxin and glutathione peroxidase, respectively) although co-exposure impaired induction. Similarly, apoptosis was inhibited by co-exposure, to which may have contributed a synergistic upregulation of tissue metalloproteinase inhibitor, β-actin and a lipid transport protein. The regulation factors of nine out of eleven identified proteins of different types revealed antagonistic or synergistic effects between Cd and B[a]P at the prospected doses after 24 h of exposure. The results indicate that co-exposure to Cd and B[a]P may enhance toxicity by impairing specific responses and not through cumulative damage.     

Mitochondrial dysfunction, oxidative stress and apoptotic induction in microglial BV-2 cells treated with sodium arsenate

The treatment of microglial BV-2 cells with sodium arsenate(As(V):0.1-400 μmol/L — 48 hr)induces a dose-dependent response.The neurotoxic effects of high concentrations of As(V)(100,200 and 400 μmol/L) are characterized by increased levels of mitochondrial complexesⅠ,Ⅱ,and Ⅳ followed by increased superoxide anion generation.Moreover,As(V) triggers an apoptotic mode of cell death,demonstrated by an apoptotic SubG1 peak,associated with an alteration of plasma membrane integrity.There is also a decrease in transmembrane mitochondrial potential and mitochondrial adenosine triphosphate ATP.It is therefore tempting to speculate that As(V) triggers mitochondrial dysfunction,which may lead to defective oxidative phosphorylation subsequently causing mitochondrial oxidative damage,which in turn induces an apoptotic mode of cell death.     

Tributyltin chloride results in dorsal curvature in embryo development of Sebastiscus marmoratus via apoptosis pathway

Tributyltin (TBT) is a ubiquitous marine environmental contaminant characterized primarily by its reproductive toxicity. However, the embryotoxicity of TBT has not been extensively described, especially in fishes. The aim of this study was to investigate the developmental toxicity of waterborne TBT at environmental levels (0, 0.1, 1, and 10 ng L⁻¹ as Sn) on Sebastiscus marmoratus embryos. Our study showed that TBT reduced the hatchability and caused apparent morphological abnormalities including dorsal curvature, severely twisted tails and pericardial edema. In addition, localized apoptosis was found in the tail regions of embryos after TBT exposure. The study provided a possible mechanistic link between apoptosis and TBT-induced twisted tails abnormality. TBT exposure induced retinoid X receptor α expression in S. marmoratus embryos at the 0.1 and 1 ng L⁻¹ group, which would be responsible for the increasing apoptotic cells induced by TBT. The results of the present study have widespread implications for environmental ecological assessment, management and the etiology of developmental defects.     

Cypermethrin has the potential to induce hepatic oxidative stress, DNA damage and apoptosis in adult zebrafish (Danio rerio)

Cypermethrin (CYP), a widely used Type II pyrethroid pesticide, is one of the most common contaminants in the freshwater aquatic system. We studied the effects of CYP exposure on the induction of hepatic oxidative stress, DNA damage and the alteration of gene expression related to apoptosis in adult zebrafish. Hepatic mRNA levels for the genes encoding antioxidant proteins, such as Cu/Zn-Sod, Mn-Sod, Cat, and Gpx, were significantly upregulated when zebrafish were exposed to various concentrations of CYP for 4 or 8 days. In addition, the main genes related to fatty acid β-oxidation and the mitochondrial genes related to respiration and ATP synthesis were also significantly upregulated after exposure to high concentrations (1 and 3 μg L⁻¹) of CYP for 4 or 8 days. Moreover, in a comet assay of zebrafish hepatocytes, tail DNA, tail length, tail moment and Olive tail moment increased in a concentration-dependent manner. The significant induction (p < 0.01) of all four parameters observed with CYP concentrations of 0.3 μg L⁻¹ or higher suggests that heavy DNA damage was induced even at low levels. Furthermore, several apoptosis- related genes, such as p53, Apaf1 and Cas3, were significantly upregulated after CYP exposure, and Bcl2/Bax expression ratio decreased, especially in groups treated with 1 and 3 μg L⁻¹ CYP for 8 days. Taken together, our results suggested that CYP has the potential to induce hepatic oxidative stress, DNA damage and apoptosis in zebrafish. This information will be helpful in fully understanding the mechanism of aquatic toxicology induced by CYP in fish.     

Modulation of the DNA repair system and ATR-p53 mediated apoptosis is relevant for tributyltininduced genotoxic effects in human hepatoma G2 cells

The toxic effects of tributyltin (TBT) have been extensively documented in several types of cells, but the molecular mechanisms related to the genotoxic effects of TBT have still not been fully elucidated. Our study showed that exposure of human hepatoma G2 cells to 1-4 μmol/L TBT for 3 hr caused severe DNA damage in a concentration-dependent manner. Moreover, the expression levels of key DNA damage sensor genes such as the replication factor C, proliferating cell nuclear antigen and poly (ADP-ribose) polymerase-1 were inhabited in a concentration-dependent manner. We further demonstrated that TBT induced cell apoptosis via the p53-mediated pathway, which was most likely activated by the ataxia telangiectasia mutated and rad-3 related (ATR) protein kinase. The results also showed that cytochrome c, caspase-3, caspase-8, caspase-9, and the B-cell lymphoma 2 were involved in this process. Taken together, we demonstrated for the first time that the inhibition of the DNA repair system might be more responsible for TBT-induced genotoxic effects in cells. Then the generated DNA damage induced by TBT initiated ATR-p53-mediated apoptosis.     

ZnO nanoparticles induced cytotoxicity on human pulmonary adenocarcinoma cell line LTEP-a-2

Novel nanoparticles (NPs) such as zinc oxide (ZnO) NPs are widely produced and applied in our daily lives at a rapid pace. Thus, the toxicity of ZnO NPs should be monitored as an important standard for environmental risk assessment. Here we assessed the in vitro cytotoxicity of ZnO NPs on human pulmonary adenocarcinoma cells LTEP-a-2 by tetrazolium salt colorimetric assay of cell proliferation in the presence or absence of ZnO NPs. ZnO NPs-induced morphological changes in LTEP-a-2 cells were examined by light and scanning electron microscopy. The mechanism by which ZnO NPs impose the cytotoxic effect was investigated by a combination of active oxygen test, lactose dehydrogenase-release assay, and apoptosis detection. Results showed that ZnO NPs significantly inhibited the proliferation and induced evident morphological changes (cell shrinkage and chromosome condensation) in LTEP-a-2 cells. Additionally, ZnO NPs increased the level of intracellular reactive oxygen species and induced the formation of apoptotic vesicles as well as the lysis of cell nuclei. Zn²⁺ ions released from ZnO NPs into aqueous solution are important components that exert cytotoxic effects on LTEP-a-2 cells. This study provides new insights to the cytotoxicity of ZnO NPs against human health.     

Elevated 5-hydroxymethycytosine and cell apoptosis induced by tetrachloro-1,4-benzoquinone in mouse embryonic stem cells

<正>Pentachlorophenol(PCP)has been extensively used as a fungicide,bactericide,herbicide,molluscicide。algaecide and insecticide worldwide(Ahlborg and Thunberg,1980:Choudhury et al.,1986).Although PCP is primarily used as a preservative for wood and wood products,it has been also used in a variety of other products,including adhesives,construction materials,leather and paper.PCP is environmentally persistent with a half-life of up to 6-7 months in soil and water systems(Law