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PM2.5 induces ferroptosis in human endothelial cells through iron overload and redox imbalance
2019
Wang, Yan | Tang, Meng
PM2.5 is becoming a worldwide environmental problem, which profoundly endangers public health, thus progressively capturing public attention this decade. As a fragile target of PM2.5, the underlying mechanisms of endothelial cell damage are still obscure. According to the previous microarray data and signaling pathway analysis, a new form of cell death termed ferroptosis in the current study is proposed following PM2.5 exposure. In order to verify the vital role of ferroptosis in PM2.5-induced endothelial lesion and further understand the potential mechanism involved, intracellular iron content, ROS release and lipid peroxidation, as well as biomarkers of ferroptosis were detected, respectively. As a result, uptake of particles increases cellular iron content and ROS production. Meanwhile, GSH depletion, and the decrease of GSH-Px and NADPH play significant roles in PM2.5-induced endothelial cell ferroptosis. Moreover, significantly changed expression of TFRC, FTL and FTH1 hinted that dysfunction of iron uptake and storage is a major inducer of ferroptosis. Importantly, index monitored above can be partially rescued by lipid peroxidation inhibitor ferrostatin-1 and iron chelator deferoxamine mesylate, which mediated antiferroptosis activity mainly depends on the restoration of antioxidant activity and iron metabolism. In conclusion, our data basically show that PM2.5 enhances ferroptosis sensitivity with increased ferroptotic events in endothelial cells, in which iron overload, lipid peroxidation and redox imbalance act pivotal roles.
显示更多 [+] 显示较少 [-]Bioaccumulation and metal-associated biomarker responses in a freshwater mussel, Dreissena polymorpha, following short-term platinum exposure
2019
Brand, Sarel J. | Erasmus, Johannes H. | Labuschagne, Marelize | Grabner, Daniel | Nachev, Milen | Zimmermann, Sonja | Wepener, V. | Smit, Nico | Sures, Bernd
Due to the increasing presence of platinum (Pt) in the environment, the caveat arises to identify its toxic potential in species at risk of being exposed – especially those found in aquatic environments where pollutants tend to accumulate. Comprehensive characterisation of possible adverse effects following exposure of aquatic organisms to Pt remains elusive. To address this, Zebra mussels (Dreissena polymorpha) were exposed to a range of Pt(IV) concentrations (0.1, 1, 10, 100 and 1000 μg/L) for one and four days, respectively, after which bioaccumulation was quantified and compared to alterations in biomarker profiles relevant to metal toxicity i.e. glutathione-S-transferase (GST) and catalase (CAT) activity, lipid peroxidation and metallothionein (MT) induction. Despite pre-conditioning of the tanks, Pt recovery in the exposure media was found to be 36% (0.1 μg/L), 42% (1 μg/L), 47% (10 μg/L), 68% (100 μg/L) and 111% (1000 μg/L) due to biological and non-biological processes. Pt concentrations in dried mussel soft tissue increased with exposure concentrations and were 20–153 times higher compared to quantified Pt concentrations in the exposure media. CAT activity was significantly increased in the tissue of mussels exposed to 0.1–100 μg/L Pt after Day 1 while the lowest effect concentration (LOC) for this response on both Day 1 and Day 4 was 0.1 μg/L. The effect on the GST activity was less pronounced but demonstrated a similar trend. However, enhanced lipid peroxidation was measured in the tissue of mussels exposed to ≥0.1 μg/L on Day 4. Bioaccumulation of Pt was also associated with a concentration-dependent increase in Pt-MT. Although these effects occurred at Pt levels higher than those present in the environment, it indicates that Pt has the ability to cause aberrancies in metal-associated biomarker profiles.
显示更多 [+] 显示较少 [-]Alleviation of the effect of salinity on growth and yield of strawberry by foliar spray of selenium-nanoparticles
2019
Zahedi, Seyed Morteza | Abdelrahman, Mostafa | Hosseini, Marjan Sadat | Hoveizeh, Narjes Fahadi | Tran, Lam-son Phan
The present study investigated the beneficial role of selenium-nanoparticles (Se-NPs) in mitigating the adverse effects of soil-salinity on growth and yield of strawberry (Fragaria × ananassa Duch.) plants by maneuvering physiological and biochemical mechanisms. The foliar spray of Se-NPs (10 and 20 mg L⁻¹) improved the growth and yield parameters of strawberry plants grown on non-saline and different saline soils (0, 25, 50 and 75 mM NaCl), which was attributed to their ability to protect photosynthetic pigments. Se-NPs-treated strawberry plants exhibited higher levels of key osmolytes, including total soluble carbohydrates and free proline, compared with untreated plants under saline conditions. Foliar application of Se-NPs improved salinity tolerance in strawberry by reducing stress-induced lipid peroxidation and H₂O₂ content through enhancing activities of antioxidant enzymes like superoxide dismutase and peroxidase. Additionally, Se-NPs-treated strawberry plants showed accumulation of indole-3-acetic acid and abscisic acid, the vital stress signaling molecules, which are involved in regulating different morphological, physiological and molecular responses of plants to salinity. Moreover, the enhanced levels of organic acids (e.g., malic, citric and succinic acids) and sugars (e.g., glucose, fructose and sucrose) in the fruits of Se-NPs-treated strawberry plants under saline conditions indicated the positive impacts of Se-NPs on the improvement of fruit quality and nutritional values. Our results collectively demonstrate the definite roles of Se-NPs in management of soil salinity-induced adverse effects on not only strawberry plants but also other crops.
显示更多 [+] 显示较少 [-]Effects of mixtures of anticancer drugs in the benthic polychaete Nereis diversicolor
2019
da Fonseca, Tainá Garcia | Abessa, Denis M.S. | Bebianno, Maria João
The increasing consumption of anticancer drugs through single and/or combinatory chemotherapy worldwide raised concern regarding their toxicity burden in coastal zones. The toxicity of a mixture of three compounds involving the drugs cisplatin (CisPt), cyclophosphamide (CP) and tamoxifen (TAM) was determined on the marine polychaete Nereis diversicolor exposed to an increasing range of their concentrations, respectively: Mix A: 0.1 + 10 + 0.1 ng L−1; Mix B: 10 + 100 + 10 ng L−1; Mix C: 100 + 500 + 25 ng L−1; Mix D: 100 + 1000 + 100 ng L−1. Different endpoints were assessed, including disturbance in the burrowing behaviour, neurotoxicity (acetylcholinesterase – AChE activity), antioxidant enzymes (superoxide dismutase – SOD; catalase – CAT; selenium-dependent glutathione peroxidase – Se-GPx and total glutathione peroxidases T-GPx activities), biotransformation metabolism (glutathione-S-transferases - GST), lipid peroxidation (LPO) and genotoxicity (DNA damage). Biological effects of the mixtures of anticancer compounds on N. diversicolor were compared with previous studies about effects on the same biological model under single-drug exposure conducted with the same molecules. Regarding SOD activity, TAM showed an antagonist effect over CisPt and CP in mixtures C and D. In Mix D, there was a synergistic effect of TAM and CisPt that inhibited CAT activity and an additive interaction of CisPt and CP on the Phase II biotransformation enzyme. Drugs in Mix A also suppressed polychaetes' GST activity, although different from the respective single-drug responses, besides able to induce T-GPx activity, that was not sufficient to avoid oxidative damage and mid-grade DNA damage. Due to the absence of burrowing impairment in Mix A, mechanisms involved in neurotoxicity were other than the one driven by AChE alterations. At the intermediary concentrations (Mix B and C), only LPO occurred. Data from drugs individually may not predict the risks provided by mixtures.
显示更多 [+] 显示较少 [-]Effects of perinatal exposure to BPA, BPF and BPAF on liver function in male mouse offspring involving in oxidative damage and metabolic disorder
2019
Meng, Zhiyuan | Tian, Sinuo | Yan, Jin | Jia, Ming | Yan, Sen | Li, Ruisheng | Zhang, Renke | Zhu, Wentao | Zhou, Zhiqiang
Bisphenols (BPs) are common environmental pollutants that are ubiquitous in the natural environment and can affect human health. In this study, we explored the effects of perinatal exposure to BPA, BPF and BPAF on liver function involving in oxidative damage and metabolic disorders in male mouse offspring. We found that BPA exposure impairs the antioxidant defense system, increases lipid peroxidation, and causes oxidative damage in the liver. Furthermore, the levels of 13 metabolites were significantly altered following BPA exposure. We found that BPF exposure significantly increased the expression and activity of CAT, suggesting disturbances in the antioxidant defense system. Moreover, BPF exposure led to metabolic disorders in the liver due to changes in the levels of 8 key metabolites. Exposure to BPAF caused no negative effects on oxidative damage, but altered the levels of β-glucose and glycogen. In summary, perinatal exposure to BPA, BPF and BPAF differentially influence oxidative damage and metabolic disorders in the livers of male mouse offspring. The impact of early life exposure to BPs now warrants future investigations.
显示更多 [+] 显示较少 [-]Tris(1,3-dichloro-2-propyl) phosphate accelerated the aging process induced by the 4-hydroxynon-2-enal response to reactive oxidative species in Caenorhabditis elegans
2019
Wang, Chen | An, Jing | Bai, Yingchen | Li, Hui | Chen, Haibo | Ou, Dong | Liu, Yongdi
Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) has been frequently detected in environmental media and biological samples. However, knowledge of its adverse health consequences is limited. In the current study, Caenorhabditis elegans (C. elegans, L1 larvae) were exposed to TDCPP at environmentally relevant concentrations (control, 0.1, 1, 100 and 1000 μg L⁻¹) for 72 h to explore any association between TDCPP and the aging process. Some of the degenerative age-related indicators were observed, including locomotion behaviors and lifespan. As crucial biomarkers of aging, the accumulation of lipofuscin, and lipid peroxidation (LPO) products exemplified by 4-hydroxynon-2-enal (4-HNE) were detected. This product forms as a result of oxidative stress, as confirmed by an N-acetyl-L-cysteine (NAC) pharmacological assay. Moreover, a significant increase in reactive oxide species (ROS) production in a dose-dependent manner using a fluorescent probe was observed. For the underlying molecular mechanism of the above aging phenotypes, significantly upregulated transcription of genes related to antioxidant systems, especially a subset of glutathione S-transferase (gst-5, gst-6, gst-9, gst-10, gst-19, gst-24, gst-26, gst-29, gst-33, and gst-38), was found by RNA-Seq and further confirmed by RT-qPCR. The elevated glutathione S-transferase (GST) was attributed to the significant increase in 4-HNE because mutations in gst-5 and gst-24 inhibited the conjugation of GSTs with 4-HNE. Therefore, GST play an indispensable role in the detoxification process of TDCPP exposure and further confirmed LPO accumulation at the molecular mechanism level. In conclusion, TDCPP accelerated the aging process induced by the LPO products, 4-HNE, response to reactive oxidative species in C. elegans.
显示更多 [+] 显示较少 [-]Biomarker responses in oysters Crassostrea hongkongensis in relation to metal contamination patterns in the Pearl River Estuary, southern China
2019
Chan, Cheuk Yan | Wang, Wen-Xiong
The Pearl River Estuary (PRE) is the third largest estuary in China, where estuarine organisms are under metal stress at various biological levels. Based on the metal concentrations measured in oyster Crassostrea hongkongensis, we documented a change in dominance of metal contamination from Cd, Cr, Cu, Ni and Zn to Ag, Cd, Cu and Zn. In general, metal concentrations were higher in upstream stations and displayed a clear up-downstream gradient. Compared to the historical values, we noted the reductions in Cd, Cr and Ni concentrations, and the changing inputs due to evolving industrial activities were responsible for shaping the metal contamination profile in the PRE region. Along with metal concentrations, a suite of biomarkers was analyzed. Among the metals measured in the oyster tissues, Ag, Cd, Cu, Ni and Zn showed the strongest associations with pro-oxidant and oxidative stress responses (superoxide dismutase, lipid peroxidation and lysosomal membrane destabilization) and detoxification responses (glutathione and metallothionein), suggesting that the present metal contamination still exerts significant amount of stress in biota in the PRE. Metal contamination in estuaries in China is still severe compared to other countries, therefore continuous efforts should be taken to monitor the changing metal profiles with necessary control and remediation measures.
显示更多 [+] 显示较少 [-]Oxidative stress in the galaxiid fish, Galaxias maculatus, exposed to binary waterborne mixtures of the pro-oxidant cadmium and the anti-oxidant diclofenac
2019
McRae, Nicole K. | Gaw, Sally | Brooks, Bryan W. | Glover, Chris N.
Chemical mixtures represent environmentally-realistic exposures of contaminants to aquatic biota. However, there remains a limited understanding of how toxicant mixtures may impact biological function, relative to their individual components. In the current study, oxidative stress responses of the freshwater galaxiid fish inanga (Galaxias maculatus) were examined following exposure to the pro-oxidant trace metal cadmium (2 or 9 μg L⁻¹), and the anti-oxidant pharmaceutical drug diclofenac (770 μg L⁻¹), individually or in simple binary mixtures. Cadmium exposure in the absence of diclofenac significantly decreased renal catalase activity, increased hepatic catalase activity, decreased renal superoxide dismutase (SOD) and decreased glutathione-S-transferase activity, effects that are suggestive of anti-oxidant defense inhibition and/or generation of increased reactive oxygen species. Diclofenac exposure in the absence of cadmium resulted in a decreased renal lipid peroxidation, consistent with its known anti-oxidant properties. The presence of waterborne diclofenac altered the effects of cadmium on catalase activity in the liver, SOD activity in the gill, and lipid peroxidation in the liver. Co-exposure with cadmium modulated diclofenac effects on lipid peroxidation in the kidney. These data indicate the capacity of each of these toxicants to offset biological effects of the other when both co-occur in urban waters at specific concentrations. This study also demonstrates the complexity of outcomes in contaminant mixtures, even when these stressors are presented as simple binary combinations.
显示更多 [+] 显示较少 [-]Protective effects of a novel pyrazolecarboxamide derivative against lead nitrate induced oxidative stress and DNA damage in Clarias gariepinus
2019
Soliman, Hamdy A.M. | Abū al-Saʻūd, Muḥammad Ḥāmid Muʻawwaḍ | Lee, Jae-seong | Sayed, Alaa El-Din H.
Pyrazole derivatives display diverse biological and pharmacological activities. The aim of this study is to investigate the antioxidant properties of a novel pyrazolecarboxamide derivative (4-amino-N-[(4-chlorophenyl)]-3-methyl-1-phenyl-1H-thieno [2, 3-c] pyrazole-5-carboxamide) in African catfish, Clarias gariepinus, exposed to 1 mg/L PbNO₃. Fish were intramuscularly injected with pyrazole-5-carboxamidederivative according to the following groupings: Group 1 (control), Group 2 (1 mg/L lead nitrate), Group 3 (1 mg/L lead nitrate + 5 mg pyrazole derivative/kg body weight), and Group 4 (1 mg/L lead nitrate + 10 mg pyrazole derivative/kg body weight) for two weeks and four weeks. Lead nitrate (1 mg/L) caused significant elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, uric acid, cholesterol, and glucose-6-phosphate dehydrogenase (G6PDH) compared to the control group after two and four weeks of exposure, while serum total lipids, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly reduced compared to the control group. Furthermore, levels of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) and total antioxidant capacity (TAC) were reduced in group 2 compared to the control group. However, in group 2, hepatic lipid peroxidation (LPO) and DNA fragmentation percentage were significantly increased compared to the control group. Histopathological changes in the liver of lead-exposed groups included marked disturbance of hepatic tissue organization, degeneration of hepatocytes, dilation of blood sinusoids and the central vein as well as necrosis. Injection of pyrazole derivative for two weeks and four weeks reversed alterations in biochemical parameters, antioxidant biomarkers, lipid peroxidation, hepatic DNA damage, and histopathological changes in liver tissue induced by 1 mg/L lead nitrate. This amelioration was higher in response to high-dose pyrazole derivative (10 mg) at the fourth week of exposure, showing concentration-and time-dependency. Overall, the sensitized derivative pyrazolecarboxamide is likely a useful tool to minimize the effects of lead toxicity due to its potent antioxidant activity.
显示更多 [+] 显示较少 [-]Negligible effects of microplastics on animal fitness and HOC bioaccumulation in earthworm Eisenia fetida in soil
2019
Wang, Jie | Coffin, Scott | Sun, Chengliang | Schlenk, Daniel | Gan, Jay
As one type of the most widespread and long-lasting anthropogenic contaminants, microplastics have become a global environmental concern. While numerous studies have demonstrated effects of microplastics on aquatic organisms, the potential influence on terrestrial faunas is relatively less known, even though soil is a primary recipient and sink of plastics. In this study, earthworm Eisenia fetida was exposed to different levels (0, 1, 5, 10, and 20% d.w.) of polyethylene (PE, ≤300 μm) and polystyrene (PS, ≤250 μm) particles in an agricultural soil to evaluate the oxidative stress. Fluorescence imaging, after dying with Nile Red, clearly indicated the ingestion of PE and PS particles by E. fetida. Exposure to PE or PS particles at the highest rate (20%) for 14 d significantly (p < 0.05) increased the activity of catalase and peroxidase and the level of lipid peroxidation, while inhibited the activity of superoxide dismutase and glutathione S-transferase in E. fetida. However, no discernible effect was detected at amendment rates ≤10% for the majority of biochemical endpoints, suggesting that microplastic-induced oxidative stress would not occur in E. fetida under most environmental conditions. The influence of microplastics on bioaccumulation of PAHs and PCBs was also evaluated in E. fetida exposed to different levels (0, 0.1, 1, 5, and 10% d.w.) of PE and PS particles. The tissue concentrations of PAHs and PCBs were reduced in the presence of microplastics at amendment rates ≥1%, suggesting that microplastics did not act as a carrier to enhance contaminant uptake. This was attributed to competitive sorption of microplastics for contaminants and the specific feeding behavior of earthworm. Biodynamic model analysis confirmed that ingestion of microplastics contributed negligibly to contaminant bioaccumulation. Findings of this study suggested that under environmentally relevant conditions, microplastics should not cause significant toxic effects to E. fetida, nor enhance its accumulation of hydrophobic contaminants.
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