ENVIRONMENTAL TOXICOLOGY
·
2020
·Vol. 35
·期 9
·982-990
·
IF 3.118
Liyang Yao,Yizhou Tang,Bolu Chen,Wuding Hong,Xinyue Xu,Yang Liu,Zoraida P. Aguilar,Hengyi Xu
In this work, we aimed to evaluate the adverse effects and the mechanism of intestinal barrier caused by titanium dioxide nanoparticles (TiO 2 NPs). Here, the effects of two different dosages (300 and 1200 mg/kg) of TiO 2 NPs on female mice (n = 5) were investigated. After 28-day oral exposure, the results of Ti content were significantly increased in the ileum in comparison with the control. The histopathological structure index of the ileum was significantly changed after TiO 2 NPs exposure; villi height and crypt depth were decreased and increased, respectively. Meanwhile, TiO 2 NPs treatment also significantly altered the transcription levels of genes. First, the GATA-3 and STAT-4 were upregulation and downregulation, respectively. Second, gene expressions of the Zonula Occludens-1, claudin ( CLDN ) -12 , occludin, and myosin light chain kinase were significantly upregulated, while the CLDN-3 was decreased. Finally, the caspase-3 , caspase-9 , and caspase-12 were upregulated. The results of TUNEL staining indicated apoptosis in the ileum. In general, TiO 2 NPs treatment significantly changed the intestine physical barrier in a dose-dependent manner. The toxicity of TiO 2 NPs could be through the imbalance in the Th1/Th2.
研究领域:
毒理学
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免疫学
·
分子生物学
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2019
·Vol. 34
·期 5
·666-673
·
IF 2.649
Xia Wang,Chenqian Zhou,Bingnan He,Baida Kong,Lai Wei,Rong Wang,Jiajia Lin,Yiyan Shao,Jianbo Zhu,Yuanxiang Jin,Zhengwei Fu
Fluorotelomer alcohols (FTOHs) are fluorinated intermediates used in manufacturing specialty polymer and surfactants, with 8:2 FTOH the homologue of largest production. FTOHs were found to pose acute toxicity, hepatotoxicity, nephrotoxicity, developmental toxicity and endocrine-disrupting risks, whereas research regarding immunotoxicity and its underlying mechanism, especially on specific immune cells is limited. Here, we investigated the immunotoxicity of 8:2 FTOH on immature immune cells in an in vitro system. We observed that exposure of HL-60 cells, a human promyelocytic leukemic cell line, to 8:2 FTOH reduced cell viability in a dose- and time-dependent manner. In addition, 8:2 FTOH exposure caused G1 cell cycle arrest in HL-60 cells, while it showed no effect on apoptosis. Exposure to 8:2 FTOH inhibited the mRNA expression of cell cycle-related genes, including CCNA1 , CCNA2 , CCND1 , and CCNE2 . Moreover, exposure to 8:2 FTOH inhibited the mRNA expression of granulocytic differentiation-related genes of CD11b , CSF3R , PU.1 , and C/EPBε in HL-60 cells . Furthermore, 8:2 FTOH exhibited no effect on intracellular ROS level, while hydralazine hydrochloride (Hyd), one reactive carbonyl species (RCS) scavenger, partially blocked 8:2 FTOH-caused cytotoxicity in HL-60 cells. Overall, the results obtained in the study show that 8:2 FTOH poses immunotoxicity in immature immune cells and RCS may partially underline its mechanism.
研究领域:
毒理学
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免疫学
·
分子生物学
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2019
·Vol. 35
·期 2
·159-166
·
IF 2.649
Xia Wang,Lai Wei,Jianbo Zhu,Bingnan He,Baida Kong,Yuanxiang Jin,Zhengwei Fu
Tetrabromoethylcyclohexane (TBECH) has been linked to endocrine disruption, hepatotoxicity, and reproductive toxicity. However, its immunotoxicity remains largely unknown. In the present study, RAW 264.7 cells, mouse macrophage cell line, were exposed to TBECH. MTT assays showed that TBECH significantly enhanced lactate dehydrogenase (LDH) release in RAW 264.7 cells. The mRNA expression of some proapoptotic genes was upregulated by TBECH. Accordingly, TBECH elevated caspase-3 activity. In addition, TBECH upregualted the mRNA levels of some pro-inflammatory cytokines, whereas it downregulated LPS-stimulated mRNA expression of these cytokines. Moreover, TBECH downregulated the mRNA expression of selected antigen presenting-related genes. Furthermore, TBECH increased reactive oxygen species level, reduced glutathione content and the activities of superoxide dismutase and catalase, and upregulated the mRNA expression of selected oxidative stress-related genes. The obtained data demonstrated that TBECH exhibits immunotoxicity in macrophages, and will help to evaluate its health risks.
研究领域:
毒理学
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免疫学
·
细胞生物学
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2020
·Vol. 35
·期 10
·1091-1099
·
IF 3.118
Dantong Jia,Xiuwen Li,Sen Du,Ning Xu,Wenming Zhang,Ruyi Yang,Yunhai Zhang,Yide He,Yongjun Zhang
Various pollutants co-exist in the aquatic environment such as carbamazepine (CBZ) and copper (Cu), which can cause complex effects on inhabiting organisms. The toxic impacts of the single substance have been studied extensively. However, the studies about their combined adverse impacts are not enough. In the present study, zebrafish were exposed to environmental relevant concentrations of CBZ (1, 10, and 100 μg/L), Cu (0.5, 5, and 10 μg/L) and the mixtures (1 μg/L CBZ + 0.5 μg/L Cu, 10 μg/L CBZ + 5 μg/L Cu, 100 μg/L CBZ + 10 μg/L Cu) for 45 days, the effects on nervous and antioxidant systems of zebrafish were investigated. The results demonstrated that, in comparison with single exposure group, the combined presence of CBZ and Cu exacerbated the effect of antioxidant system (the ability of inhibition of hydroxyl radicals (IHR), superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST)) but not nervous system (Acetylcholinesterase [AChE]). The qPCR results supported the changes of corresponding enzymes activities. Hepatic histopathological analysis verified the results of biomarkers. Our work illustrated that the toxicity of mixed pollutants is very complicated, which cannot simply be inferred from the toxicity of single pollutant, and calls for more co-exposure experiments to better understanding of the co-effects of pollutants on aquatic organisms.
研究领域:
环境毒理学
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水生生物学
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药理学
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2022
·Vol. 37
·期 7
·1551-1562
·
IF 4.109
Dan Song,Yuan Liu,Yaxin Yao,Feng Liu,Wenjing Tao,Xiaolong Zhou,Runsheng Li,Xiaowei Zhang,Xiangchen Li
The aim of this study was to assess the protective effect and potential mechanism of melatonin against bisphenol A (BPA)-induced apoptosis and oxidative damage in FLK-BLV cells. The results showed that BPA reduced cell viability in a dose- and time-dependent manner, caused cell shrinkage and induced oxidative stress and apoptosis in FLK-BLV cells, which were effectively reversed by melatonin. In addition, BPA caused autophagy flux impairment, which was confirmed by the increased of LC3-II and p62 levels, whereas melatonin treatment effectively reduced p62 levels under BPA treatment, and reversed apoptosis-related protein expression patterns caused by BPA. However, inhibition of autophagy by CQ partially abolished the protective effect of melatonin on apoptosis, suggesting that melatonin against BPA-induced oxidative injury and apoptosis by activating autophagy pathway. Moreover, we found that melatonin inhibited BPA-induced the activation of p38 MAPK, which was comparable to SB203580 pretreatment, and companied by the activation of autophagy and decreases of apoptosis when compared to BPA alone, indicating that melatonin protected against BPA-induced apoptosis partially through the p38 MAPK-autophagy pathway. In conclusion, these results suggest that melatonin may prevent BPA-induced FLK-BLV cell damage by inhibiting p38/MAPK signaling pathway and activating autophagy, and it could be a potential therapeutic compound in preventing BPA-induced cell damage.
研究领域:
细胞生物学
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毒理学
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药理学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2014
·Vol. 31
·期 4
·496-504
·
IF 2.562
Zhu Enhui,Chen Na,Liu MengYun,Li Jia,Li Dan,Yang Yongsheng,Zhang Ying,He DeFu
As an organochlorine insecticide, endosulfan has been widely banned or restricted, but it is still largely used in many developing countries. Previous studies have shown multiple adverse health effects of endosulfan. However, the neurotoxicity of endosulfan has not been fully elucidated. In this study, endosulfan isomers (α-/β-endosulfan) and their major metabolites (endosulfan sulfate, endosulfan diol, and endosulfan lactone) were, respectively, exposed to human neuroblastoma SH-SY5Y cells. Results showed that both α-endosulfan and β-endosulfan caused decrease of cell viability and morphological damages in a dose-dependent manner. Their median effective concentrations (EC 50s ) were respectively 79.6 μM (α-endosulfan) and 50.37 μM (β-endosulfan) for 72 h exposure. EC 50s of α/β-endosulfan mixture were lower than that of the single isomer. However, EC 50s of its metabolites were higher than that of technical endosulfan. Endosulfan and its metabolites caused increases of reactive oxygen species and the lipid peroxidation, but decrease of superoxide dismutase in a dose-dependent manner. These results indicate that α-endosulfan exhibits higher neurotoxicity than β-endosulfan. Mixture of endosulfan isomers shows stronger cytotoxicity than the single isomer. After endosulfan is degraded, cytotoxicity of its metabolites decreases gradually. The neurotoxicity of endosulfan and its metabolites is closely related to oxidative damage and antioxidative deficit. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 496–504, 2016.
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PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2016
·Vol. 32
·期 4
·1202-1212
·
IF 2.868
Xincheng Yan,Xiaolong Xu,Mingchun Guo,Shasha Wang,Shang Gao,Shanshan Zhu,Rui Rong
The extensive applications of ZnO nanoparticles (nano ZnO) and dimethoate (DM) have increased the risk of humans' co-exposure to nano ZnO and DM. Here, we report the synergistic effect of nano ZnO and DM on their biodistribution and subacute toxicity in mice. Nano ZnO and DM had a synergistic toxicity in mice. In contrast, bulk ZnO and DM did not cause an obvious synergistic toxicity in mice. Although nano ZnO was low toxic to mice, coexposure to nano ZnO and DM significantly enhanced DM-induced oxidative damage in the liver. Coadministration of nano ZnO with DM significantly increased Zn accumulation by 30.9 ± 1.9% and DM accumulation by 45.6 ± 2.2% in the liver, respectively. The increased accumulations of DM and Zn in the liver reduced its cholinesterase activity from 5.65 ± 0.32 to 4.37 ± 0.49 U/mg protein and induced hepatic oxidative stress. Nano ZnO had 3-fold or 2.4-fold higher binding capability for serum albumin or DM, respectively, than bulk ZnO. In addition, serum albumin significantly increased the binding capability of nano ZnO for DM by approximately four times via the interaction of serum albumin and DM. The uptake of serum albumin- and DM-bound nano ZnO by the macrophages significantly increased DM accumulation in mice. Serum albumins play an important role in the synergistic toxicity of nano ZnO and DM. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1202–1212, 2017.
研究领域:
环境毒理学
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纳米技术
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药理学
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2018
·Vol. 34
·期 1
·22-29
·
IF 2.491
Yi Zhang,Cuiyuan Jin,Xiaoyu Wang,Manlu Shen,Jiajie Zhou,Sisheng Wu,Zhengwei Fu,Yuanxiang Jin
Propamocarb (PM) is a type of fungicide, which is widely used in the greenhouse-based production of vegetables and fruits globally. It has been considered to have generally low toxicity. However, the teratogenicity or neurotoxicity for mammals remains unclear. In this study, we aimed to explore its effect on the secretion of neurotransmitters and behavioral impairments. Male adult mice were exposed to 10 and 40 mg/L PM for 2 weeks (acute exposure) or 3 and 10 mg/L PM for 10 weeks (chronic exposure). It was observed that acute or chronic exposure to PM changed the levels of serotonin (5-HT) and dopamine in the serum and colon and the transcription of TPH2 and DRD2 in the colons of mice. In addition, the locomotor test, the open field test, and the Morris water maze analysis also showed that acute exposure to PM caused behavioral impairments to some extent. The results obtained in the present study indicated that PM has the potential to induce neurotoxicity in animals.
研究领域:
毒理学
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神经科学
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药理学
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2013
·Vol. 29
·期 12
·1460-1470
·
IF 2.708
Mingbao Feng,Ruijuan Qu,Ying Li,Zhongbo Wei,Zunyao Wang
Hexabromobenzene (HBB) is a novel brominated flame retardant (BFR) with ample evidence of its ubiquitous existence in the aquatic ecosystems. However, to date, the toxicological effects of this BFR on fish have been inadequately researched. The present study was conducted, based on an in vivo model, to investigate HBB-induced biochemical changes in liver and gill tissues of Carassius auratus after medium-term exposure to different concentrations (10, 150, and 300 mg/kg) for 7, 14, and 25 days. Oxidative stress was evoked evidently for the prolonged exposure, demonstrated by significant inhibition in antioxidant enzymes activities including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and glutathione S-transferase, and a decrease in reduced glutathione level, as well as simultaneous elevation in malondialdehyde content. Moreover, Na + , K + -ATPase activity, and protein level were remarkably reduced in fish tissues. Based on the integrated biomarker response, the toxic potency in each treatment was distinguished, and the more severe stress was mainly noted with the increasing concentrations and the extending durations. It was also observed that liver exhibited more pronounced alterations in biochemical parameters than gill, probably indicating the vulnerability of liver to HBB-triggered oxidative stress. Taken together, the results of this study clearly showed that HBB was capable of inducing oxidative stress and inhibiting Na + , K + -ATPase activity in different tissues of C. auratus after medium-term exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1460–1470, 2014.
研究领域:
环境毒理学
·
水生生态学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2022
·Vol. 37
·期 5
·1093-1103
·
IF 4.109
Fengfan Liu,Xiang Cheng,Shuang Wu,Bei Hu,Chen Yang,Shufen Deng,Qiwen Shi
Exposure to nickel oxide nanoparticles (NiONPs), which have been widely produced and applied in industry, leads to adverse pulmonary and systemic effects. The aim of this study is to investigate the involvement of apoptosis and ferroptosis in NiONPs-induced acute lung injury (ALI). Intratracheal instillation of NiONPs into mice elevated the levels of pro-inflammatory cytokines, neutrophils, and proteins in the bronchoalveolar lavage fluid, and triggered apoptosis and ferroptosis in the lung tissues. Consistently, NiONPs-induced apoptosis and ferroptosis were observed in in vitro experiments using human lung epithelial cells. Activating transcription factor 3 (ATF3), a stress-inducible transcription factor, was upregulated by NiONPs exposure in both murine lung tissues and human lung epithelial cells. Moreover, human lung epithelial cells with ATF3 deficiency exhibited a lower level of apoptosis and ferroptosis when exposed to NiONPs. Collectively, our findings demonstrated that ATF3 was responsive to NiONPs exposure, and promoted NiONPs-induced apoptosis and ferroptosis in lung epithelial cells, indicating that ATF3 is a potential biomarker and therapeutic target for NiONPs-associated ALI.
研究领域:
毒理学
·
肺科学
·
分子生物学
·
细胞生物学
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2022
·Vol. 37
·期 9
·2201-2213
·
IF 4.109
Qi Xiong,Xiang Tian,Congyue Xu,Baomiao Ma,Wei Liu,Binlian Sun,Qin Ru,Xiji Shu
PM 2.5 exposure has been demonstrated to correlate with neurological disorders recently. Ferroptosis is recognized as a newly found programmed form of cell death associated with neurodegenerative diseases, while glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis. However, the relationship between PM 2.5 -induced neurotoxicity and ferroptosis is still unclear. The current study aims to investigate if ferroptosis is involved in neurotoxicity post PM 2.5 exposure and its underlying mechanism. The PM 2.5 -treated neuronal Neuro-2a (N2A) and SH-SY5Y cells were applied to the current study. The results showed that PM 2.5 significantly increased the neuronal cell death, yet the ferroptosis antagonist Ferrostain-1 (Fer-1) markedly decreased the cell death induced by PM 2.5 . Western blot further confirmed that ferroptosis was triggered post PM 2.5 treatment in N2A cells by decreasing expressions of GPX4 and ferritin heavy chain (FTH), as well as enhancing expressions of ferritin light chain (FTL) and transferrin receptor protein (TFRC). Meanwhile, PM 2.5 treatment augmented neuronal oxidative damage and mitochondrial dysfunction. The bioinformatic analysis indicated that CREB could be the regulator of GPX4, and our results showed that ERK/CREB pathway was down-regulated in N2A cells post PM 2.5 treatment. The addition of ERK1/2 agonist post PM 2.5 treatment significantly inhibit ferroptosis via increasing the expression of GPX4. Taken together, the present study demonstrated that PM 2.5 -induced ferroptosis via inhibiting ERK/CREB pathway, and these findings will advance our knowledge of PM 2.5 -induced cytotoxicity in the nervous system.
研究领域:
神经科学
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毒理学
·
细胞生物学
·
环境健康
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2021
·Vol. 37
·期 1
·101-119
·
IF 4.119
Caixia Wang,Zhangyu Gu,Xueyan Gu,Xinyue Tan,Shuang Wang,Rui Zhang,Ruifen Li,Mingkun Sun,Chunyan Gui,Sheng Li,Yixing Ye,Jianhua Ma,Li Su,Changhao Liang
The aim of this study was to investigate the protective effects of Nano-Se against nickel (Ni)-induced hepatotoxicity and the potential mechanism. Hence, we constructed in vivo and in vitro models of Ni-induced hepatotoxicity. Sprague–Dawley (SD) rats were exposed to nickel sulfate (NiSO 4 , 5.0 mg/kg, i.p.) with or without Nano-Se (0.5, 1, and 2 mg/kg, oral gavage) co-administration for 14 days, and HepG2 cells were exposed to NiSO 4 (1500 μM) with or without Nano-Se (20 μM) for 24 h. Nano-Se obviously prevented Ni-induced hepatotoxicity indicated by ameliorating pathological change and decreasing Ni accumulation in rat livers. Ni induced a significant increase in hepatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSH-Px), and malondialdehyde (MDA) level, decreased the glutathione (GSH) content while compared to those in the control group. Nano-Se administration improved the hepatic antioxidant capacity through increase hepatic GSH contents and GSH-Px activity, decrease the activities of SOD, CAT, and MDA level. Nano-Se improved the cell viability, decreased active oxygen (ROS) generation and ameliorated morphological changes of nuclear structures in Ni-treated HepG2 cells. In addition, Nano-Se inhibited the Ni-induced increases of cytochrome c, caspase-9, cleaved caspase-3, increased PI3K and AKT phosphorylation both in vivo and in vitro. Besides, the PI3K inhibitor Y294002 could inhibit the protective effects of Nano-Se on apoptosis. Thus, Nano-Se significantly activates PI3K/AKT signaling to ameliorate apoptosis in Ni-induced hepatotoxicity.
研究领域:
毒理学
·
药理学
·
细胞生物学
·
分子生物学
·
生物化学
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PubMed
高影响因子
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