ENVIRONMENTAL TOXICOLOGY
·
2022
·Vol. 37
·期 8
·1902-1913
·
IF 4.109
Ruike Wang,Zuntao Wu,Rundong Liu,Lin Bai,Yan Lin,Yue Ba,Hui Huang
Numbers of emerging evidence suggest that lead (Pb) exposure contributes to cognitive decline and might also increase the risk of Alzheimer's disease (AD) dementia in the elderly by increasing the beta-amyloid burden. Here, we aimed to characterize the effects of Pb on the post-transcriptional regulators, microRNAs (miRNAs), which may participate in AD pathogenesis. At first, early chronic Pb exposure on neuronal miRNAs expression with increasing aging was profiled to elucidate the association of three selected miRNAs with β-site APP-cleaving enzyme 1(BACE1), a rate-limiting enzyme for β-amyloid (Aβ) production. Next, we verified changes in BACE1 were observed by regulating miRNAs expression in vitro. While Pb promoted BACE1 levels, BACE1 levels were reduced in SH-SY5Y cells with miR-124-3p mimic, suggesting for the first time that miR-124-3p/BACE1 pathway modulation is critically involved in Pb-induced AD-like amyloidogenic processing. Findings from this study could provide new insight into the molecular mechanisms of Pb-associated neurodegenerative pathogenesis from an epigenetic perspective.
研究领域:
神经科学
·
分子生物学
·
毒理学
·
表观遗传学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2021
·Vol. 37
·期 2
·201-211
·
IF 4.119
Rong Li,Hongsong Li,Qian Zhang
Purpose The damage of hyperglycemia to the retinal pigment epithelial (RPE) cells is a critical event in diabetic retinopathy (DR). Procyanidin (PC), a kind of polyphenol compounds, has shown to be effective in preventing and treating diabetes as well as its complications, in which autophagy disorder is involved in the pathological mechanism. However, it remains unclear whether PC can play a protective role in DR by regulating the autophagy of RPE. Here, the effect of PC on RPE under high glucose conditions and the role of autophagy were investigated. Materials and Methods The cell viability of ARPE-19, a human RPE cell line, was detected by cell counting kit-8 (CCK-8) and the apoptosis rate was measured by flow cytometry. The protein expressions of apoptosis markers, including Bax, Bcl-2, and Caspase-3, as well as autophagy markers including LC3, p62, p53, and mTOR were detected by Western blotting. Autophagic flux in ARPE-19 cells was detected by transfection with Ad-mCherry-GFP-LC3B. Results Under high glucose conditions, the viability of ARPE-19 was decreased and the apoptosis rate increased, the protein expressions of Bax, Caspase-3, LC3-II/LC3-I, and p-p53 were all increased and the expressions of Bcl-2, p62, and p-mTOR decreased, and autophagic flux was increased compared with that of the controls. Treatment with PC weakened all these changes caused by high glucose. When rapamycin (RPM), an autophagy agonist was added, the cell viability of ARPE-19 by PC treatment was decreased while the apoptosis was increased. Conclusions Our findings indicate that through the p53/mTOR autophagy pathway, PC may protect RPE cells from high glucose-induced injury.
研究领域:
眼科学
·
药理学
·
细胞生物学
·
糖尿病
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DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2021
·Vol. 37
·期 4
·708-719
·
IF 4.119
Dan Liu,Ye Cheng,Xueying Mei,Yanzhen Xie,Zhipeng Tang,Jianli Liu,Xiangyu Cao
Acrolein is a ubiquitous environmental pollutant that produced by the incomplete combustion of cigarette smoke, forest fires, petroleum fuels, plastic materials, and cooking fumes. Inhalation is a common form of people exposure to acrolein, increasing evidence demonstrates that acrolein impairs the cardiovascular system by targeting vascular endothelial cells. However, the molecular mechanism of the cytotoxicity of acrolein exposure on vascular endothelial cells remains unclear. This work focused on the toxicity of acrolein on human umbilical vein endothelial cells (HUVECs). The molecular mechanism was studied based on oxidative stress, DNA damage response (DDR), and mitochondrial apoptosis pathways. After HUVECs were treated with 12.5, 25, and 50 μM acrolein for 24 h, cell viability, cell colony formation, mitochondrial membrane potential, and adenosine triphosphate content significantly reduced, and acrolein increased intracellular reactive oxygen species, apoptosis rate, and 8-hydroxy-2 deoxyguanosine (8-OHdG) level. Furthermore, p38MAPK and c-Jun N-terminal kinase signaling pathways were activated in response to oxidative stress. Moreover, acrolein induced G0/G1phase arrest, promoted the expression of γ-H2AX, activated the DDR signaling pathway (Ataxia-Telangiectasia-Mutated [ATM] and Rad-3-related/Chk1 and ATM/Chk2), and triggered the consequent cell cycle checkpoints. Finally, the protein expression of Bax/Bcl-2 and cleaved Caspase-3 was up-regulated, suggesting apoptosis was induced by triggering the mitochondrial apoptosis pathway. All these results indicated that acrolein induced HUVECs cytotoxicity by regulating oxidative stress, DNA damage, and apoptosis. This study provides a novel perspective on the mechanism of acrolein-induced cardiovascular toxicity, it will be helpful for the prevention of acrolein-induced cardiovascular disease.
研究领域:
毒理学
·
细胞生物学
·
心血管科学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2021
·Vol. 37
·期 1
·41-51
·
IF 4.119
Rili Hao,Junlin Ge,Xinyu Song,Feng Li,Dongxiao Sun-Waterhouse,Dapeng Li
Cadmium (Cd) is a potent neurotoxic metal present in the environment and food. In this study, CdCl 2 (2 or 4 μM) induced cytotoxicity and neurotoxicity in PC12 cells, causing decreases in cell viability and NEP protein expression and increase in p-tau protein expression. For the first time, CdCl 2 -initiated injury was found to result from the induction of not only apoptosis but also ferroptosis, as evidenced by the increased iron content, ROS production, and mitochondrial membrane potential along with changes in the expressions of iron death-related genes (FTH1, GPX4, ASCL4, PTGS2, and NOX1) and levels of caspase9, Bax, and Bcl-2 proteins. The molecular mechanisms leading to apoptosis and ferroptosis at least included the participation of the miR-34a-5p/Sirt1 axis, in which miR-34a-5p promoted CdCl 2 -induced neurotoxicity through targeting Sirt1. Knocking out miR-34a-5p attenuated CdCl 2 -induced damage of PC12 cells, cytotoxicity and neurotoxicity. This research provides the underlying molecular mechanisms of CdCl 2 -induced damage and asserts the role of miRNAs as critical regulators.
研究领域:
神经科学
·
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2025
·
IF 3.2
Yuejie Wu,Fei Wang,Longxiang Gao,Yunfei Zhang,Lanying Wang,Yanping Luo
Arecoline is a major active alkaloid in Areca catechu L. Currently, its biological toxicity has been extensively explored using multiple models, such as cell lines, animal embryos and representatives of rodent and non-rodent species. However, the intergenerational impacts of this compound on aquatic invertebrate species remain still unclear. Thus, in this study, using Aedes aegypti as the model insect, we evaluated the toxicity of arecoline to the larvae and its subsequent effects on the developmental parameters of the parental ( F 0 ) and offspring ( F 1 ) generations. Arecoline exhibited a high toxicity to A. aegypti larvae with the LC 50 value of 72.68 μg/mL via acute exposure for 48 h. As a result, the cumulative pupation rate of F 0 decreased significantly by ranging from 12.96% to 38.50% with the increase of arecoline concentration from 51.63 to 63.27 μg/mL as compared with that of the blank control. Similarly, the F 0 cumulative emergence rate and the average egg number per female exhibited reductions of 15.30%–43.88% and 26.32%–45.10%, respectively. Meanwhile, leg deformities of F 0 adults were observed as the main visible morphological defects with a maximum rate value of 11.89% at 63.27 μg/mL of arecoline. In contrast, the lifecycle parameters for F 0 mentioned above were not significantly affected in the F 1 generation. In addition, Gene Ontology (GO) analysis of the transcriptome data demonstrated that arecoline-induced leg deformities were associated with extracellular chitin-related biological processes. Furthermore, five chitin synthesis pathway genes ( G6PI , GFAT , GNPNA , UAP and CHS ) of F 0 adults were significantly down-regulated with ranging from 1.62 to 7.80 folds of the control adults. Correspondingly, the activity of chitin synthetase was significantly inhibited by 72.88% after arecoline exposure. As expected, the chitin contents of leg-deformed adults and their legs were also evidently reduced by 61.13% and 65.44%, respectively. These results imply that acute exposure of arecoline is of high toxicity to A. aegypti larvae and affected the subsequent intergenerational growth and development of F 0 rather than F 1 , and that a decrease in chitin synthesis was involved in arecoline-induced leg deformities of A. aegypti .
研究领域:
毒理学
·
昆虫学
·
分子生物学
·
环境科学
·
昆虫生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2024
·
IF 4.4
Lei Huang,Jiayi Wang,Jieqin Yu,Mengxuan Bian,Xingdong Xiang,Guanjie Han,Weisin Chen,Ning Wang,Jun Ge,Shunyi Lu,Jian Zhang
Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to abnormal oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation, making the OP-related bone healing a significant clinical challenge. As the osteogenic differentiation ability of bone marrow mesenchymal stem cells (BMSCs) is closely related to bone regeneration; currently, this study assessed the effects of Picein on BMSCs in vitro and bone regeneration in osteoporotic bone defect in vivo. Cell viability was determined by CCK-8 assay. The production of (ROS), malonaldehyde, superoxide dismutase activities, and glutathione was evaluated by using commercially available kits, and a flow cytometry analysis was adopted to detect macrophage polarization. Osteogenic capacity of BMSCs was evaluated by alkaline phosphatase (ALP) activity, ALP staining, and Alizarin red S staining. The expression of osteogenic-related proteins (OPN, Runx-2, OCN) and osteogenic-related genes (ALP, BMP-4, COL-1, and Osterix) were evaluated by Western blotting and real-time PCR (RT-PCR). In addition, proliferation, migration ability, and angiogenic capacity of human umbilical vein endothelial cells (HUVECs) were evaluated by EdU staining, scratch test, transwell assay, and tube formation assay, respectively. Angiogenic-related genes (VEGF, vWF, CD31) were also evaluated by RT-PCR. Results showed that Picein alleviated erastin-induced oxidative stress, enhanced osteogenic differentiation capacity of BMSCs, angiogenesis of HUVECs, and protects cells against ferroptosis through Nrf2/HO-1/GPX4 axis. Moreover, Picein regulate immune microenvironment by promoting the polarization of M2 macrophages in vitro. In addition, Picein also reduce the inflammation levels and promotes bone regeneration in osteoporotic bone defect in OP rat models in vivo. Altogether, these results suggested that Picein can promote bone regeneration and alleviate oxidative stress via Nrf2/HO-1/GPX4 pathway, offering Picein as a novel antioxidant agent for treating osteoporotic bone defect.
研究领域:
药理学
·
骨生物学
·
氧化应激
·
干细胞研究
·
炎症
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2024
·
IF 4.4
Hong Wang,Jianmin Sang,Zhongyao Ji,Yang Yu,Shaowei Wang,Yang Zhu,Huitao Li,Yiyan Wang,Ren-shan Ge
Chlorinated bisphenol A (BPA) derivatives are formed during chlorination process of drinking water, whereas bisphenol S (BPS) and brominated BPA and BPS (TBBPA and TBBPS) were synthesized for many industrial uses such as fire retardants. However, the effect of halogenated BPA and BPS derivatives on glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) remains unclear. The inhibitory effects of 6 BPA derivatives in the inhibition of human and rat 11β-HSD1 were investigated. The potencies for inhibition on human 11β-HSD1 were TBBPA (IC 50 , 3.87 μM) = monochloro BPA (MCBPA, 4.08 μM) = trichloro BPA (TrCBPA, 4.41 μM) > tetrachloro BPA (TCBPA, 9.75 μM) > TBBPS (>100 μM) = BPS (>100 μM), and those for rat 11β-HSD1 were TrCBPA (IC 50 , 2.76 μM) = MCBPA (3.75 μM) > TBBPA (39.58 μM) > TCBPA = TBBPS = BPS. All these BPA derivatives are mixed/competitive inhibitors of both human and rat enzymes. Molecular docking studies predict that MCBPA, TrCBPA, TCBPA, and TBBPA all bind to the active site of human 11β-HSD1, forming hydrogen bonds with catalytic residue Ser170 except TCBPA. Regression of the lowest binding energy with IC 50 values revealed a significant inverse linear regression. In conclusion, halogenated BPA derivatives are mostly potent inhibitors of human and rat 11β-HSD1, and there is structure-dependent inhibition.
研究领域:
药理学
·
毒理学
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2019
·Vol. 34
·期 6
·742-752
·
IF 2.649
Shijin Wu,Zhenzhen Zhu,Jialin Chen,Mei Wu,Lequan Qiu
Brominated flame retardants (BFRs) are supposed to act as disruptors of cell signaling, but the underlying mechanisms remain less clear. Human bronchial epithelial cells (BEAS-2B) were used to investigate the toxic effect and gene expression changes induced by tetrabromobisphenol A (TBBPA). By genome-wide approaches with Illumina RNA-seq, 87 genes were identified to exhibit ≥1.5-fold changes in expression after treatment by TBBPA for 48 h, among which, 79 were upregulated and 8 were downregulated. Gene ontology (GO) annotation enriched unigenes were divided into three clusters: biological process (BP), cellular component (CC) and molecular function (MF). Pathway analysis showed that NF-κB, TNF signaling, toll-like receptor, MAPK signaling and B-cell receptor were the most prominent pathways affected by TBBPA, which play key roles in regulating cell proliferation and cell differentiation, inflammatory response. Finally, for verifying the accuracy of microarray analysis, qRT-PCR was used to analyze the transcription level of key genes in the above signaling pathways, and ELISA assay confirmed the effect of TBBPA on the levels of CXCL-2, CCL-3, CCL-4, IL-1β, TNF-α, and IL-6. These findings provided important information for further exploitation of the mechanisms under-lying BFR-induced adverse health effects.
研究领域:
毒理学
·
分子生物学
·
环境健康科学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2022
·Vol. 37
·期 8
·1840-1852
·
IF 4.109
Huijie Chen,Yue Zhang,Mengmeng Zou,Xiaowei Sun,Xiaodan Huang,Shiwen Xu
Dibutyl phthalate (DBP) is a phthalic acid ester (PAE) that has posed a health hazard to the organisms. Naringenin (NRG) is a flavanone compound that has shown protection against several environmental chemicals through suppression of oxidative stress and activation of phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) signaling pathway. Herein, swine testis (ST) cells were treated with 1.8 μM of DBP or/and 25.39 nM of NRG for 24 h, we described the discovery path of NRG inhibition on apoptosis in DBP-exposed ST cells through targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN). We first found that the anti-apoptosis effect of NRG is dependent on mitochondrial pathway through flow cytometry and related gene/protein expression, and then we detected PI3K/AKT pathway-related gene/protein expression, and established a computational docking assay between NRG and PTEN. We found that NRG specifically binds to three basic residues (His93, Lys125, Lys128) of P loop in PTEN, as well as phosphatase domains (Asp92, His93, Cys124, Lys125, Ala126, Lys128, and Arg130) in active dephosphorylation pockets, thereby reducing PTEN level and activating PI3K/AKT signaling pathway, and further inhibiting oxidative stress and mitochondrial pathway apoptosis. Taken together, our results push forward that NRG deserves further attention as a potential antagonistic therapy against DBP through targeting PTEN to inhibit oxidative stress and activate PI3K/AKT signaling pathway.
研究领域:
毒理学
·
细胞生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2018
·Vol. 34
·期 2
·141-149
·
IF 2.491
Xia Wang,Baida Kong,Bingnan He,Lai Wei,Jianbo Zhu,Yuanxiang Jin,Yudong Shan,Weitao Wang,Chunqiang Pan,Zhengwei Fu
8:2 Fluorotelomer alcohol (8:2 FTOH) is widely used in houseware and industrial goods and is ubiquitous in the surrounding environment. 8:2 FTOH has been linked to hepatoxicity, nephrotoxicity, and reproductive toxicity, as well as endocrine-disrupting effects. However, as of yet, the research regarding immunotoxicity of 8:2 FTOH remains largely limited. In the present study, adult male C57BL/6 mice were administered with 10, 30, and 100 mg/kg/d 8:2 FTOH by gavage for 28 days to investigate its immunotoxicity in vivo. The results showed that exposure to 8:2 FTOH caused increases in liver weight and histological changes in the liver, including vacuolation, cell swelling, immune cell infiltration, karyopyknosis and nuclear swelling. No histological change in either the spleen or the thymus was observed after administration of 8:2 FTOH. In addition, exposure to 8:2 FTOH reduced the concentration of IL-1β in serum, and mRNA levels of IL-1β, IL-6 , and TNF-α in both the thymus and spleen. CXCL-1 mRNA expression was downregulated in both the liver and thymus after 8:2 FTOH administration, while only IL-1β mRNA expression was upregulated in the liver. Moreover, the exposure of primary cultured splenocytes to 8:2 FTOH inhibited the ConA-stimulated proliferation of splenocytes at concentrations of 30 and 100 μM, and the LPS-stimulated proliferation of splenocytes at 100 μM. Furthermore, 8:2 FTOH inhibited the level of secreted IFN-γ in ConA-stimulated splenocytes. The results obtained in the study demonstrated that 8:2 FTOH posed potential immunotoxicity and liver injury in mice. Our findings will provide novel data for the health risk assessment of 8:2 FTOH.
研究领域:
毒理学
·
免疫学
·
环境健康
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2023
·Vol. 38
·期 6
·1226-1238
·
IF 4.5
Lu Chen,Meng Qi,Linlin Zhang,Fuchang Yu,Dayong Tao,Chunyan Xu,Shiwen Xu
Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer and an endocrine disruptor. Microplastics (MPs) are pathogenic small plastic particles and abundant in the aqueous environment. The problem of residual hazards of plastic products is worthy of study, especially the joint exposure of a variety of plastic-related products to the toxic effect. We used 200 mg/kg DEHP and 10 mg/L MPs to establish exposure model in vivo and 2 mM DEHP and 200 μg/L MPs to establish AML12 cell exposure model in vitro. In vivo study results showed that compared with the control group (NC) group, DEHP and MPs significantly increased the contents of malondialdehyde and hydrogen peroxide, and significantly decreased the contents of glutathione and the activity of superoxide dismutase, total antioxidant capacity, catalase and glutathione peroxidase. The level of oxidative stress was further aggravated after combined exposure. The reactive oxygen species level of AML12 exposed to DEHP and MPs in vitro was significantly higher than NC group, and the combined exposure was significantly higher than the single exposure. The in vivo and in vitro also confirmed that DEHP and MPs could significantly increase the mRNA and protein levels of apoptosis markers and necroptosis markers and there was an additive effect. After N-acetylcysteine treatment in vitro, the above-mentioned oxidative stress level and cell damage decreased significantly. This study provided a reference for advocating the reduction of the mixed use of plastic products, and provided a basis for preventing the harm of plastic products residues.
研究领域:
毒理学
·
环境科学
·
细胞生物学
✓ 已验证
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
·
水生生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）