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Constant light exposure causes oocyte meiotic defects and quality deterioration in mice
2020
Zhang, Huiting | Yan, Ke | Sui, Lumin | Nie, Junyu | Cui, Kexin | Liu, Jiahao | Zhang, Hengye | Yang, Xiaogan | Lu, Kehuan | Liang, Xingwei
Artificial light at night (ALAN) exposes us to prolonged illumination, that adversely affects female reproduction. However, it remains to be clarified how prolonged light exposure affects oocyte meiotic maturation and quality. To this end, we exposed female mice to a constant light (CL) of 250 lux for different durations. Our findings showed that CL exposure for 7 weeks reduced the oocyte maturation rate. Meanwhile, CL exposure caused greater abnormalities in spindle assembly and chromosome alignment and a higher rate of oocyte aneuploidy than the regular light dark cycle. CL exposure also induced oxidative stress and caused mitochondrial dysfunction, which resulted in oocyte apoptosis and autophagy. Notably, our results showed that CL exposure reduced the levels of α-tubulin acetylation, DNA methylation at 5 mC, RNA methylation at m⁶A and histone methylation at H3K4me2 but increased the levels of histone methylation at H3K27me2 in oocytes. In summary, our findings demonstrate that constant bright light exposure causes oocyte meiotic defects and reduces cytoplasmic quality. These results extend the current understanding of ALAN-mediated defects in female reproduction.
Показать больше [+] Меньше [-]Monobutyl phthalate (MBP) can dysregulate the antioxidant system and induce apoptosis of zebrafish liver
2020
Jiao, Yaqi | Tao, Yue | Yang, Yang | Diogene, Tuyiringire | Yu, Hui | He, Ziqing | Han, Wei | Chen, Zhaobo | Wu, Pan | Zhang, Ying
In this paper, the acute toxicity of monobutyl phthalate (MBP), the main hydrolysis product of dibutyl phthalate, on adult zebrafish liver antioxidant system was studied. Compared the toxicity effect of MBP and DBP by histopathology and apoptosis experiments, we speculated that the toxic effects of DBP on animals may be caused by its metabolite MBP. The results indicated that the antioxidant Nrf2-Keap1 pathway was insufficient to resist MBP-induced hepatotoxicity and led to an imbalance of membrane ion homeostasis and liver damage. Decreased cell viability, significant tissue lesions and early hepatocyte apoptosis were observed in the zebrafish liver in MBP exposure at high concentration (10 mg/L). The activities of antioxidant enzymes and ATPases in zebrafish liver were inhibited with increased malondialdehyde (MDA) content and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Integrated biomarker response (IBR) calculation results indicated that MBP mainly inhibited catalase (CAT) activity. Simultaneously, the expression of antioxidant-related genes (SOD, CAT, GPx, Nrf2, HO-1) was down-regulated, while apoptosis-related genes (p53, bax, cas3) were significantly up-regulated.
Показать больше [+] Меньше [-]Characterization, pro-inflammatory response and cytotoxic profile of bioaerosols from urban and rural residential settings in Pune, India
2020
Roy, Ritwika | Jan, Rohi | Joshi, Uttara | Bhor, Renuka | Pai, Kalpana | Satsangi, P Gursumeeran
Microbiota associated with airborne particulate matter (PM) is an important indicator of indoor pollution as they can be pathogenic and cause serious health threats to the exposed occupants. Present study aimed to investigate the level of culturable microbes associated with PM and their toxicological characterization in urban and rural houses of Pune city. Highest concentration of bacterial aerosols observed to be associated with PM₁₀ size fraction in urban site (2136 ± 285 CFU/m³) whereas maximum fungal concentration has been measured in rural houses (1521 ± 302 CFU/m³). Predominantly found bacterial species were Bacillus sp., S. aureus, and Pseudomonas aeruginosa and fungal species were Aspergillus sp., Cladosporium sp., and Penicillium sp. in both urban and rural residential premises. Concentration of endotoxin measured using the kinetic Limulus Amebocyte Lysate assay exhibited that the level of endotoxin in both urban and rural sites are associated with household characteristics and the activities performed in indoor as well as outdoor. Cell free DTT assay confirmed the ability of these airborne microbes to induce the production of reactive oxygen species (ROS) varying along with the types of microorganisms. On exposure of A549 cells to airborne microbes, a significant decrease in cell viability was observed in terms of both necrosis and apoptosis pathway. Elevated production of nitric oxide (NO) and proinflammatory cytokines in epithelial cells and macrophages clearly suggest the inflammatory nature of these airborne microbes. Results derived from the present study demonstrated that the indoor air of urban and rural houses of Pune is contaminated in terms of microbial load. Therefore, attention should be paid to control the factors favoring the microbial growth in order to safeguard the health of exposed inhabitants.
Показать больше [+] Меньше [-]Long-term bisphenol S exposure aggravates non-alcoholic fatty liver by regulating lipid metabolism and inducing endoplasmic reticulum stress response with activation of unfolded protein response in male zebrafish
2020
Qin, Jingyu | Ru, Shaoguo | Wang, Weiwei | Hao, Liping | Ru, Yiran | Wang, Jun | Zhang, Xiaona
Environmental chemical exposures have been implicated as risk factors for the development of non-alcoholic fatty liver (NAFLD). Bisphenol S (BPS), widely used in multitudinous consumer products, could disrupt lipid metabolism in the liver. This study aimed at examining the hypothesis that long-term exposure to BPS promotes the development of liver fibrosis and inflammation by means of the application of a semi-static exposure experiment that exposed zebrafish to 1, 10, and 100 μg/L BPS from 3 h post fertilization to 120 day post fertilization. Results showed that the 120-d BPS exposure elevated plasma aspartate aminotransferase and alanine aminotransferase activities, increased triacylglycerol (TAG) and total cholesterol levels in male liver, and even induced hepatic apoptosis and fibrosis. Hepatic lipid accumulation observed in the 30-d BPS-exposed zebrafish was recovered after a 90-d depuration phase, thereby indicating that long-term BPS exposure promotes the progression of simple steatosis to non-alcoholic steatohepatitis. Furthermore, BPS exposure for 120-d promoted the synthesis of TAG and lipotoxic free fatty acids by elevating the transcription of srebp1, acc, fasn, and elovl6, induced endoplasmic reticulum (ER) stress with increasing expression levels of unfolded protein response (UPR) genes (perk, hsp5, atf4a, and ddit3), and then stimulated the expression of two key autophagy genes (atg3 and lc3) and inflammatory genes (il1b and tnfα). It is indicated that BPS can induce the development of steatohepatitis via the activation of the PERK-ATF4a pathway of the UPR. Data gathered suggest that environmental pollutants-induced ER stress with the activation of UPR can potentially trigger the NAFLD development in males. Overall, our study provided new sights into understanding of the adverse health effects of metabolism disrupting chemicals.
Показать больше [+] Меньше [-]Application of advanced HepG2 3D cell model for studying genotoxic activity of cyanobacterial toxin cylindrospermopsin
2020
Hercog, Klara | Štampar, Martina | Štern, Alja | Filipič, Metka | Žegura, Bojana
Cylindrospermopsin (CYN) is an emerging cyanotoxin increasingly being found in freshwater cyanobacterial blooms worldwide. Humans and animals are exposed to CYN through the consumption of contaminated water and food as well as occupational and recreational water activities; therefore, it represents a potential health threat. It exhibits genotoxic effects in metabolically active test systems, thus it is considered as pro-genotoxic. In the present study, the advanced 3D cell model developed from human hepatocellular carcinoma (HepG2) cells was used for the evaluation of CYN cyto-/genotoxic activity. Spheroids were formed by forced floating method and were cultured for three days under static conditions prior to exposure to CYN (0.125, 0.25 and 0.5 μg/mL) for 72 h. CYN influence on spheroid growth was measured daily and cell survival was determined by MTS assay and live/dead staining. The influence on cell proliferation, cell cycle alterations and induction of DNA damage (γH2AX) was determined using flow cytometry. Further, the expression of selected genes (qPCR) involved in the metabolism of xenobiotics, proliferation, DNA damage response, apoptosis and oxidative stress was studied. Results revealed that CYN dose-dependently reduced the size of spheroids and affected cell division by arresting HepG2 cells in G1 phase of the cell cycle. No induction of DNA double strand breaks compared to control was determined at applied conditions. The analysis of gene expression revealed that CYN significantly deregulated genes encoding phase I (CYP1A1, CYP1A2, CYP3A4, ALDH3A) and II (NAT1, NAT2, SULT1B1, SULT1C2, UGT1A1, UGT2B7) enzymes as well as genes involved in cell proliferation (PCNA, TOP2α), apoptosis (BBC3) and DNA damage response (GADD45a, CDKN1A, ERCC4). The advanced 3D HepG2 cell model due to its more complex structure and improved cellular interactions provides more physiologically relevant information and more predictive data for human exposure, and can thus contribute to more reliable genotoxicity assessment of chemicals including cyanotoxins.
Показать больше [+] Меньше [-]Investigation of the effects of dichlorvos poisoning on AMPK signaling pathway in chicken brain tissues
2020
Xiao, Yanyu | Zheng, Xibang | Li, Guyue | Zhou, Changming | Wu, Cong | Xu, Zheng | Hu, Guoliang | Guo, Xiaoquan | Li, Lin | Cao, Huabin | Latigo, Vincent | Liu, Ping
Dichlorvos is a common crop insecticide widely used by people which causes extensive and serious environmental pollution. However, it has been shown that organophosphorus poisoning causes energy metabolism and neural disorders. The overall purpose of this study was to investigate the damage to brain tissue and the changes in AMPK signaling pathway-related gene expression after dichlorvos poisoning in chickens. White-feathered broiler chickens, as the research subjects of this experiment, were divided into three groups: control group, low-dose group (77.5% dichlorvos at 1.13 mg/kg dose) and high-dose group (77.5% dichlorvos at 10.2 mg/kg dose). Clinical symptoms were observed after modeling, and an integrative analysis was conducted using HE staining microscopy, immune-histochemical microscopy, electron microscopy and PCR arrays. The results showed that the high-dose group had more obvious dyspnea, salivation, convulsion and other neurological phenomena. Pathological sections showed that nuclear disintegration of neurons was most obvious in the low-dose group, and apoptosis of brain cells was most obvious in the high-dose group, and the mitochondrial structure was destroyed in the two poisoned group, i.e. low-dose group and high-dose group. PCR arrays showed that AMPK signaling pathway was inhibited and the expressions of genes involved in energy metabolism (ACACA and PRKAA1) were significantly changed. Furthermore, genes associated with protein synthesis (EIF4EBP1) were significantly upregulated. FASN and HMGCR expressions were significantly increased. There were significant changes in the expressions of cell cycle-related genes (STK11, TP53 and FOXO3). Organophosphate poisoning can cause a lot of nuclear disintegration of brain neurons, increases cell apoptosis, disrupts the energy metabolism of mitochondrial structure, and inhibits the AMPK signaling pathway. These results provide a certain idea and basis for studying the mechanism of AMPK signaling after organophosphorus poisoning and provide a research basis for the prevention and treatment of organophosphorus poisoning.
Показать больше [+] Меньше [-]MicroRNA-382-5p is involved in pulmonary inflammation induced by fine particulate matter exposure
2020
Zhang, Xinwei | Zhang, Yanshu | Meng, Qingtao | Sun, Hao | Wu, Shenshen | Xu, Jie | Yun, Jun | Yang, Xi | Li, Bin | Zhu, Hao | Xue, Ling | Li, Xiaobo | Chen, Rui
Exposure to atmospheric particulate matter (PM) has been related to the increasing incidence and mortality of pulmonary diseases, where microRNAs (miRNAs) play significant roles in these biological and pathological processes. In the present study, we found that miR-382-5p played an anti-inflammatory role in pulmonary inflammation induced by fine particulate matter (PM₂.₅) or diesel exhaust particles (DEPs) in vitro and in vivo. The expression level of miR-382-5p was downregulated, while its target gene, namely CXCL12, was elevated in HBE cells after exposure to PM₂.₅ or DEPs. Mechanistically, PM₂.₅ or DEPs exposure increased CXCL12/MMP9 expression via miR-382-5p inhibition, subsequently triggered pulmonary inflammation. Furthermore, antagonizing the function of CXCL12 significantly reduced the expression of MMP9 and local inflammation induced by PM₂.₅ or DEPs. PM₂.₅ or DEPs caused apoptosis and G1 phase arrest could be partially restored by overexpression of miR-382-5p and antagonism of CXCL12. In a murine model, enhanced miR-382-5p expression effectively reduced expression levels of CXCL12, MMP9 and inflammatory cytokines, hereby protected lung tissues against PM₂.₅ or DEPs-induced lesions. Collectively, the miR-382-5p/CXCL12/MMP9 pathway may provide a mechanism, which mediates inflammatory response to PM₂.₅ or DEPs exposure.
Показать больше [+] Меньше [-]Effects of different mobile phone UMTS signals on DNA, apoptosis and oxidative stress in human lymphocytes
2020
Gulati, Sachin | Kosik, Pavol | Durdik, Matus | Skorvaga, Milan | Jakl, Lukas | Markova, Eva | Belyaev, Igor
Different scientific reports suggested link between exposure to radiofrequency radiation (RF) from mobile communications and induction of reactive oxygen species (ROS) and DNA damage while other studies have not found such a link. However, the available studies are not directly comparable because they were performed at different parameters of exposure, including carrier frequency of RF signal, which was shown to be a critical for appearance of the RF effects. For the first time, we comparatively analyzed genotoxic effects of UMTS signals at different frequency channels used by 3G mobile phones (1923, 1947.47, and 1977 MHz). Genotoxicity was examined in human lymphocytes exposed to RF for 1 h and 3 h using complimentary endpoints such as induction of ROS by imaging flow cytometry, DNA damage by alkaline comet assay, mutations in TP53 gene by RSM assay, preleukemic fusion genes (PFG) by RT-qPCR, and apoptosis by flow cytometry. No effects of RF exposure on ROS, apoptosis, PFG, and mutations in TP53 gene were revealed regardless the UMTS frequency while inhibition of a bulk RNA expression was found. On the other hand, we found relatively small but statistically significant induction of DNA damage in dependence on UMTS frequency channel with maximal effect at 1977.0 MHz. Our data support a notion that each specific signal used in mobile communication should be tested in specially designed experiments to rule out that prolonged exposure to RF from mobile communication would induce genotoxic effects and affect the health of human population.
Показать больше [+] Меньше [-]Hexavalent chromium induces mitochondrial dynamics disorder in rat liver by inhibiting AMPK/PGC-1α signaling pathway
2020
Yang, Qingyue | Han, Bing | Xue, Jiangdong | Lv, Yueying | Li, Siyu | Liu, Yan | Wu, Pengfei | Wang, Xiaoqiao | Zhang, Zhigang
Occupational exposure to hexavalent chromium (Cr(VI)) can cause cytotoxicity and carcinogenicity. In this study, we established a liver injury model in rats via intraperitoneal injection of potassium dichromate (0, 2, 4, and 6 mg/kg body weight) for 35 d to investigate the mechanism of Cr(VI)-induced liver injury. We found that Cr(VI) induced hepatic histopathological lesions, oxidative stress, and apoptosis and reduced the expression of mitochondrial-related regulatory factors such as adenosine 5′-monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in a dose-dependent manner. Furthermore, Cr(VI) promoted mitochondrial division and inhibited fusion, leading to increased expression of caspase-3 and production of mitochondrial reactive oxygen species. Our study demonstrates that long-term exposure to Cr(VI) induces mitochondrial dynamics disorder by inhibiting AMPK/PGC-1α signaling pathway in rat liver.
Показать больше [+] Меньше [-]Ecotoxicity of trace elements to chicken GALLUS gallus domesticus exposed to a gradient of polymetallic-polluted sites
2020
Kribi-Boukhris, Sameh EL. | Boughattas, Iteb | Zitouni, Nesrine | Helaoui, Sondes | Sappin-Didier, Valérie | Coriou, Cécile | Bussiere, Sylvie | Banni, Mohamed
Mining activity may cause heavy metal accumulation, which threatens human and animal health by their long-term persistence in the environment. This study aims to assess the impact of polymetallic pollution on chicken (Gallus domesticus) from old lead mining sites in northeast of Tunisia: Jebel Ressas (JR). Samples of soil and chickens were collected from five sites being ranked along a gradient of heavy metal contamination. Heavy metal loads were evaluated in soil samples and in chicken liver and kidney. Biochemical evaluation of oxidative stress parameters termed as Catalase (CAT), Glutathione-S-Transferase (GST), and Malondialdehydes (MDA) accumulation was monitored. Metallothionein protein level was assessed as a specific response to heavy metals. DNA alteration was achieved using MNi frequency in the investigated tissues. Finally, the evaluation of gene expression levels of CAT, GST, mt1, mt4, P53, bcl2, caspase3 and DNA-ligase was performed. Our data showed the highest loads of Cd, Cu, Zn and Pb in tissues of animals from site 3, being more pronounced in kidney. Biochemical data suggested a significant increase in antioxidant enzymes activities in all sites respect to control except in site 3 were CAT and GST were inhibited. DNA alteration was observed in all tissues being very pronounced in animals from site 3. Overall, transcriptomic data showed that genes involved in apoptosis were up-regulated in animals exposed to the most contaminated soils. Our data suggest that chicken and selected biomarkers offer a suitable model for biomonitoring assessment of heavy metals transfer through the food web in mining sites. Finally, the obtained results of heavy metals accumulation and related alterations should be carefully considered in view of the controversial relationship between distribution and toxicology of contaminants in exposed organisms.
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