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Gradual effects of gradient concentrations of polystyrene nanoplastics on metabolic processes of the razor clams
2021
Jiang, Qichen | Zhang, Wenyi
With the widespread occurrence and accumulation of plastic waste in the world, plastic pollution has become a serious threat to ecosystem and ecological security, especially to estuarine and coastal areas. Understanding the impacts of changing nanoplastics concentrations on aquatic organisms living in these areas is essential for revealing the ecological effects caused by plastic pollution. In the present study, we revealed the effects of exposure to gradient concentrations (0.005, 0.05, 0.5 and 50 mg/L) of 75 nm polystyrene nanoplastics (PS-NPs) for 48 h on metabolic processes in muscle tissue of a bivalve, the razor clam Sinonovacula constricta, via metabolomic and transcriptomic analysis. Our results showed that PS-NPs caused dose-dependent adverse effects on energy reserves, membrane lipid metabolism, purine metabolism and lysosomal hydrolases. Exposure to PS-NPs reduced energy reserves, especially lipids. Membrane lipid metabolism was sensitive to PS-NPs with contents of phosphocholines (PC), phosphatidylethanolamines (PE) and phosphatidylserines (PS) increasing and degradation being inhibited in all concentrations. High concentrations of PS-NPs altered the purine metabolism via increasing contents of guanosine triphosphate (GTP) and adenine, which may be needed for DNA repair, and consuming inosine and hypoxanthine. During exposure to low concentrations of PS-NPs, lysosomal hydrolases in S. constricta, especially cathepsins, were inhibited while this influence was improved transitorily in 5 mg/L of PS-NPs. These adverse effects together impacted energy metabolism in S. constricta and disturbed energy homeostasis, which was manifested by the low levels of acetyl-CoA in high concentrations of PS-NPs. Overall, our results revealed the effects of acute exposure to gradient concentrations of PS-NPs on S. constricta, especially its metabolic process, and provide perspectives for understanding the toxicity of dynamic plastic pollution to coastal organisms and ecosystem.
显示更多 [+] 显示较少 [-]ROS-mediated programmed cell death (PCD) of Thalassiosira pseudonana under the stress of BDE-47
2020
Zhao, Yirong | Tang, Xuexi | Qu, Fangyuan | Lv, Mengchen | Liu, Qian | Li, Jun | Li, Luying | Zhang, Bihan | Zhao, Yan
Polybrominated diphenyl ethers (PBDEs) are a series of highly persistent organic pollutants (POPs) ubiquitously distributed in marine environments. As key primary producers, microalgae are the start of PBDEs bioaccumulations and vulnerable to their toxicities. In order to deeply investigate the toxic mechanism of PBDEs on microalgal cells, the occurrence of programmed cell death (PCD) in a model diatom Thalassiosira pseudonana and its possible mediating mechanism were studied. The results indicated: cell death of T. pseudonana happened under the stress of BDE-47, which was proved to be PCD based on the correlations with three biochemical markers (DNA fragmentation, phosphatidylserine externalization and caspase activity) and three molecular markers [Metacaspase 2 gene (TpMC2), Death-associated protein gene (DAP3) and Death-specific protein 1 gene (TpDSP1)]; Furthermore, the changes of cellular ROS levels were correlated with the PCD markers and the dead cell rates, and the cell membrane and the chloroplast were identified as the major ROS production sites. Therefore, we concluded that PCD might be an important toxic mechanism of PBDEs on microalgal cells, and that chloroplast- and cell membrane-produced ROS was an important signaling molecule to mediate the PCD activation process. Our research firstly indicated microalgal PCD could be induced by PBDEs, and increased our knowledge of the toxic mechanisms by which POPs affect microalgal cells.
显示更多 [+] 显示较少 [-]Triphenyl phosphate modulated saturation of phospholipids: Induction of endoplasmic reticulum stress and inflammation
2020
Hu, Wenxin | Kang, Qiyue | Zhang, Chenhao | Ma, Haojia | Xu, Chenke | Wan, Yi | Hu, Jianying
Although triphenyl phosphate (TPHP) has been reported to disrupt lipid metabolism, the effect of TPHP on lipid saturation remains unexplored. In this study, a lipidomic analysis demonstrated decreases in the levels of poly-unsaturated phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) in RAW264.7 murine macrophage cells exposed to 10 μM TPHP. The expression of the gene encoding lysophosphatidylcholine acyltransferase 3 (Lpcat3) was significantly downregulated by 0.76 ± 0.03 and 0.70 ± 0.08-fold in 10 and 20 μM TPHP exposure groups, relative to the control group. This finding explains the observed decrease in lipid saturation. Correspondingly, exposure to 10 and 20 μM TPHP induced endoplasmic reticulum (ER) stress and inflammatory responses, which have been linked to metabolic dysfunction such as insulin resistance and hypertriglyceridemia. Therefore, TPHP may pose a risk to human health by promoting metabolic diseases.
显示更多 [+] 显示较少 [-]Hexavalent chromium induced oxidative stress and apoptosis in Pycnoporus sanguineus
2017
Feng, Mi | Yin, Hua | Peng, Hui | Liu, Zehua | Lu, Guining | Dang, Zhi
White rot fungi have been proved to be a promising option for the removal of heavy metals, understanding their toxic response to heavy metals is conducive to developing and popularizing fungi-based remediation technologies so as to lessen the hazard of heavy metals. In this study, Cr(VI)-induced oxidative stress and apoptosis in Pycnoporus sanguineus, a species of white rot fungi were investigated. The results suggested that high level of Cr(VI) promoted the formation of ROS, including H2O2, O2•− and ·OH. With the increment of Cr(VI) concentration, the SOD and CAT activity along with GSH content increased within the first 24 h, but decreased afterwards, companied with a significant enhancement of MDA content. Cr(VI)-induced oxidative damage further caused and aggravated apoptosis in Pycnoporus sanguineus, especially at Cr(VI) concentrations above 20 mg/L. Cr(VI)-induced apoptosis was involved with mitochondrial dysfunction including mitochondrial depolarization, the enhancement of mitochondrial permeability and release of cytochrome c. The early and late apoptosis hallmarks, such as metacaspase activation, phosphatidylserine (PS) externalization, DNA fragmentation and the nuclear condensation and fragmentation were observed. Moreover, we also found disturbances of ion homeostasis, which was featured by K+ effluxes and overload of cytoplasmic and mitochondrial Ca2+.Based on these results, we suggest that Cr(VI) induced oxidative stress and apoptosis in white rot fungi, Pycnoporus sanguineus.
显示更多 [+] 显示较少 [-]Impacts of chemical stress, season, and climate change on the flounder population of the highly anthropised Seine estuary (France)
2022
Laurent, Jennifer | Lavergne, Edouard | Couteau, Jérôme | Le Floch, Stéphane | Ouddane, Baghdad | Cachot, Jérôme | Davail, Blandine | Clérandeau, Christelle | Devin, Simon | Fisson, Cédric | Devaux, Alain | Amara, Rachid | Diop, Mamadou | Pichereau, Vianney | Laroche, Jean
The main objective of this study was to improve our knowledge on the responses of fish populations to multistress (diffuse pollution and warming waters) in estuaries. Adult flounders were caught in two estuaries in the Eastern English Channel: the heavily polluted Seine estuary vs the moderately contaminated Canche estuary. Fish samplings were conducted in January just before the reproduction period, and in July when gonads were at rest. The overall rise in coastal winter water temperatures detected over the Channel impairs the flounder’s phenology of reproduction in the two estuaries, inducing a delay of maturation process and probably also spawning. The higher liver histopathology index in Seine vs Canche could be the consequence of the fish exposition to a complex cocktail of contaminants in a strongly industrialized estuary. Higher levels of neurotoxicity, gill lipid peroxidation, and liver EROD activity were observed in Seine vs Canche. Furthermore, a possible impairment in mitochondrial metabolism was suggested in the Seine flounder population. We confirmed in this study the potential role of two membrane lipids (sphingomyelin and phosphatidylserine) in the resistance towards oxidative stress in Seine and Canche. Finally, we suggest that the Seine flounder population (and possibly the connected Eastern English Channel flounder populations over the French Coast) could be seriously impacted in the future by multistress: higher winter temperatures and chemical contamination.
显示更多 [+] 显示较少 [-]The dysregulation of unsaturated fatty acid-based metabolomics in the MNNG-induced malignant transformation of Het-1A cells
2022
Zhang, Hu | Liu, Qiwei | Zhao, Chao | Zhang, Ying | Wang, Shizhi | Liu, Ran | Pu, Yuepu | Yin, Lihong
Studies have shown that environmental carcinogens exerted an important function in the high incidence of esophageal cancer (EC). Nitrosamines have been identified as important environmental carcinogens for EC. This study aimed to investigate the metabolic disturbances and new key toxicological markers in the malignant transformation process of normal esophageal epithelial cells (Het-1A) induced by MNNG (N-methyl-N′-nitro-N-nitrosoguanidine). Untargeted metabolomic and lipidomic profiling analysis by using ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) were applied to explore the metabolic network alterations of Het-1A cells. The metabolomic results showed that significant alterations were observed in metabolic signatures between different generations (P5, P15, P25, P35) and the control cell group (P0). A total of 48 differential endogenous metabolites were screened and identified, mainly containing fatty acids, amino acids, and nucleotides. The differential metabolites were predominantly linked to the pathway of biosynthesis of unsaturated fatty acids metabolism. The cell lipidomic profiling revealed that the most differential lipids contained fatty acids (FAs), phosphatidylcholines (PC), phosphatidylethanolamines (PE), and phosphatidylserines (PS). The enrichment of the lipidomic pathway also confirmed that the lipid metabolism of biosynthesis of unsaturated fatty acids was the significant variation during the cell malignant transformation. Furthermore, we detected the expression of the upstream regulatory enzymes related to the unsaturated fatty acids to explore the regulation mechanism. The expression of stearoyl-CoA desaturase (SCD), ELOVL fatty acid elongase 1 (ELOVL1) promoted, and fatty acid desaturase 1 (FADS1) inhibited the key fatty acids of unsaturated fatty acids metabolism compared to the control cell group. Overall, our results revealed that lipid fatty acid metabolism was involved in the malignant transformation of Het-1A cells induced by MNNG and deepened the awareness of the carcinogenic mechanism of environmental exposure pollutants.
显示更多 [+] 显示较少 [-]Modulation of mutagenicity in Salmonella typhimurium and antioxidant properties and antiproliferative effects of fractions from Cassia fistula L. on human cervical HeLa and breast MCF-7 cancer cells
2021
Kaur, Sandeep | Kumar, Ajay | Pandit, Kritika | Kaur, Satwinderjeet
The present study investigated the antimutagenic, antioxidant, and antiproliferative properties of extracts of Cassia fistula prepared by sequentially fractionation of 80% methanolic (CaLM extract) extract of C. fistula leaves, namely CaLH (hexane), CaLC (chloroform), CaLE (ethyl acetate), CaLB (n-butanol), and CaLA (aqueous) fractions. The antimutagenicity of the fractions was tested against mutagens viz. S9-independent, namely 4-nitro-o-phenylenediamine (TA98) and sodium azide (TA100) and S9-dependent, 2-AF (2-aminofluorene). Among the tested fractions, CaLE fraction showed a potent efficacy with an inhibition percentage of 85.57% (TA98) and 89.93% (TA100) against the mutagenicity induced by 2-aminofluorene. The CaLE fraction could significantly scavenge free radicals in various assays, namely DPPH, lipid peroxidation inhibition, and superoxide anion radical scavenging assays with an IC₅₀ of 12.80, 144, and 257.3 μg/ml respectively. The antiproliferative potential of the effective CaLE fraction was assessed using MTT assay against HeLa and MCF-7 cancer cells with GI₅₀ value of 243.4 and 324.6 μg/ml respectively. The fraction exhibited remarkable apoptosis-inducing effects through the externalization of phosphatidylserine in HeLa cells as analyzed by annexin V-FITC/PI double staining assay. The HPLC analysis of CaLE revealed the presence of catechin, epiafzelechin, and chlorogenic acid which are responsible for its antimutagenic and antiproliferative efficacy. Graphical abstract
显示更多 [+] 显示较少 [-]Antiproliferative and apoptogenic effects of Cassia fistula L. n-hexane fraction against human cervical cancer (HeLa) cells
2020
Kaur, Sandeep | Pandit, Kritika | Chandel, Madhu | Kaur, Satwinderjeet
The current study was performed to evaluate the antiproliferative and apoptosis-inducing potential of n-hexane fraction from Cassia fistula L. (Caesalpinioideae) fruits. The antiproliferative property of the fraction was determined by MTT assay against cancer cell lines including HeLa, MG-63, IMR-32, and PC-3 with GI₅₀ value of 97.69, 155.2, 143, and 160.2 μg/ml respectively. The fraction was further explored for its apoptotic effect using confocal, SEM, and flow cytometry studies in HeLa cells. It was observed that the treatment of fraction revealed fragmentation of DNA, chromatin condensation, membrane blebbing, and formation of apoptotic bodies in a dose-dependent manner. The fraction also showed a remarkable increase in the level of ROS, mitochondrial depolarization and G₀/G₁ phase cell cycle arrest, and induction in the phosphatidylserine externalization analyzed using Annexin V-FITC/PI double staining assay in HeLa cells. Kaempferol, Ellagic acid, and Epicatechin are the major phytoconstituents present in the fraction as revealed by the HPLC. The treatment of n-hexane fraction showed downregulation in the gene expression of Bcl-2 and upregulation in the expression level of p53, Bad, and caspase-3 genes analyzed using semi-quantitative RT-PCR in HeLa cells. These results suggest that n-hexane fraction from C. fistula inhibited the proliferation of cervical cancer cells efficiently by the induction of apoptosis. Graphical abstract
显示更多 [+] 显示较少 [-]Bismuth oxide nanoparticles induce oxidative stress and apoptosis in human breast cancer cells
2021
Alamer, Ali | Ali, Daoud | Alarifi, Saud | Alkahtane, Abdullah | AL-Zharani, Mohammed | Abdel-Daim, Mohamed M. | Albasher, Gadah | Almeer, Rafa | Al-Sultan, Nouf K. | Almalik, Abdulaziz | Alhasan, Ali H | Stournaras, Christos | Hasnain, Saquib | Alkahtani, Saad
Metal nanomaterials such as bismuth oxide nanoparticles (Bi₂O₃NPs) have been extensively used in cosmetics, dental materials, pulp capping, and biomedical imaging. There is little knowledge about the health risk of Bi₂O₃NPs in humans, which warrants a thorough toxicity investigation of Bi₂O₃NPs at the cellular level. In this experiment, we investigated the cytotoxic effect of Bi₂O₃NPs on human breast cancer (MCF-7) cells over 24 and 48 h. MCF-7 cells were exposed to Bi₂O₃NPs at varying doses (0.1, 0.5, 1.0, 5, 10, 20, 40 μg/mL) for 24 and 48 h. We assessed the toxicity of Bi₂O₃NPs by measuring its effect on the viability and oxidative stress biomarkers, e.g., GSH, SOD, and catalase in MCF-7 cells. The pro-apoptotic effects of Bi₂O₃NPs on MCF-7 cells were determined via evaluating dysfunction of mitochondrial membrane potential (MMP), caspase-3 activity, externalization of phosphatidylserine, and chromosome condensation. Furthermore, apoptotic cells were evaluated using 7-AAD fluorescence stain and Annexin V-FITC. Bi₂O₃NPs induced oxidative stress in MCF-7 cells in a time- and dose-dependent manner. Bi₂O₃NPs increased the rate of both necrotic cells and apoptotic cells. In addition, the blue fluorescence of MCF-7 cells with condensed chromatin was increased in a time- and dose-dependent manner. In conclusion, the present study highlights the potential toxic effects of Bi₂O₃NPs at the cellular level and suggests further investigation of Bi₂O₃NPs before any medical purposes.
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