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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.
Show more [+] Less [-]In vitro toxicity of dimethyl phthalate to human erythrocytes: From the aspects of antioxidant and immune functions
2019
Li, Shixuan | Chi, Zhenxing | Li, Weiguo
In the study, the effects of dimethyl phthalate (DMP) on the antioxidant defense capacity and immune functions of human erythrocytes were experimentally explored. DMP affected the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) and the contents of glutathione (GSH) and malondialdehyde (MDA) in erythrocytes, thus impairing the function of antioxidant defense system of erythrocytes. When DMP concentration increased from 0 to 28 μmol L⁻¹, the SOD and GPX activities were increased firstly and then gradually decreased. When DMP concentration was below 20 μmol L⁻¹, the relative activity of SOD was enhanced by DMP and the effect was known as hormesis. The relative activity of GPX was also increased when the concentration of DMP was below 12 μmol L⁻¹. The CAT activity was more significantly inhibited by DMP than the activities of SOD and GPX, whereas the relative GSH content was increased by DMP. MDA levels were significantly changed after the exposure to DMP (0–24 μmol L⁻¹). The experimental results of the activity of SOD and CAT, and the content of MDA also suggested that DMP could inhibit the immune functions of red blood cells (RBCs), which were further proved by the decrease of two indicators (RBC-C₃b and RBC-IC) due to the destruction of C₃b receptor with immune adherence function on erythrocyte membrane. The study provides a deep understanding of the toxicity of DMP on erythrocytes.
Show more [+] Less [-]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.
Show more [+] Less [-]Di (2-ethyl hexyl) phthalate (DEHP)-induced spleen toxicity in quail (Coturnix japonica) via disturbing Nrf2-mediated defense response
2019
Yu, Lei | Li, Hui-Xin | Guo, Jian-Ying | Huang, Yue-Qiang | Wang, Hui | Talukder, Milton | Li, Jin-Long
Di(2-ethylhexyl) phthalate (DEHP), as a widely used plasticizer, is reported to have widespread environmental and global health hazards. Trace amounts of phthalates in the environment are sufficient to disrupt ecological balance and affect human health. However, DEHP-induced splenic toxicity remains in an unknown state. Therefore, to explore the mechanism of DEHP-induced splenic toxicity, male quail were employed with 0, 250, 500 and 750 mg/kg body weight DEHP by daily gastric perfusion for 45 days. Notably, splenic corpuscular border and cell gap enlargement were observed in the spleen tissue of DEHP-exposed quail under the histopathological analysis. Furthermore, DEHP induced dysregulation of oxidative stress markers by increasing malondialdehyde (MDA) content and decreasing superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities. Low concentration of DEHP (≤250 mg/kg) exposure suppressed nuclear factor-E2-related factor 2 (Nrf2) signaling pathway, while high concentration of DEHP (≥500 mg/kg) exposure activated Nrf2-mediated defense response. DEHP induced splenic oxidative stress via interfering Nrf2 signal pathway and altering the transcription of its downstream genes. In conclusion, this study suggested that DEHP induced splenic toxicity.
Show more [+] Less [-]Does salinity modulates the response of Mytilus galloprovincialis exposed to triclosan and diclofenac?
2019
Freitas, Rosa | Coppola, Francesca | Costa, Silvana | Manzini, Chiara | Intorre, Luigi | Meucci, Valentina | Soares, Amadeu M.V.M. | Pretti, Carlo | Solé, Montserrat
In the present study Mytilus galloprovincialis mussels were exposed for 28 days to three salinities: 30 (control), 25 and 35. Simultaneously, organisms at each salinity were exposed to either the antimicrobial agent Triclosan (TCS) or the pharmaceutical drug Diclofenac (DIC) at 1 μg/L. Salinity alone and exposure to PPCPs changed mussel's metabolic capacity and oxidative status, but no additive or synergetic effects resulting from the combined exposures were observed. Overall, the metabolic capacity of mussels was decreased when exposed to TCS and DIC under control salinity, which was less pronounced at salinities out of the control level. TCS had a notorious effect over glutathione peroxidase activity while DIC exposure enhanced catalase response. Such defence mechanisms were able to prevent cellular damage but still a clear reduction in GSH/GSSG ratio after PPCPs exposures indicates oxidative stress which could compromise bivalve's performance to further stressing events.
Show more [+] Less [-]Polluted water from an urban reservoir (Madín dam, México) induces toxicity and oxidative stress in Cyprinus carpio embryos
2019
Pérez-Coyotl, I. | Galar-Martínez, M. | García-Medina, S. | Gómez-Oliván, L.M. | Gasca- Pérez, E. | Martínez-Galero, E. | Islas-Flores, H. | Pérez-Pastén, Borja R. | Barceló, D. | López de Alda, M. | Pérez-Solsona, S. | Serra-Roig, M.P. | Montemurro, N. | Peña-Herrera, J.M. | Sánchez-Aceves, L.M.
The Madín Dam is a reservoir located in the municipalities of Naucalpan and Atizapán, in the metropolitan area adjacent to Mexico City. The reservoir supplies drinking water to nearby communities and provides an area for various recreational activities, including kayaking, sailing and carp fishing. Over time, the number of specimens of common carp has notably diminished in the reservoir, which receives direct domestic drainage from two towns as well as numerous neighborhoods along the Tlalnepantla River. Diverse studies have demonstrated that the pollutants in the water of the reservoir produce oxidative stress, genotoxicity and cytotoxicity in juvenile Cyprinus carpio, possibly explaining the reduction in the population of this species; however, it is necessary to assess whether these effects may also be occurring directly in the embryos. Hence, surface water samples were taken at five sites and pharmaceutical drugs, personal care products (especially sunscreens), organophosphate and organochlorine pesticides, and other persistent organic pollutants (e.g., polychlorinated biphenyls and polycyclic aromatic hydrocarbons) were identified. Embryos of C. carpio were exposed to the water samples to evaluate embryolethality, modifications in embryonic development, lipoperoxidation, the quantity of hydroperoxide and oxidized proteins, and antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase). It was found that the polluted water of the Madín Dam gave rise to embryolethality, embryotoxicity, congenital abnormalities, and oxidative stress on the common carp embryos.
Show more [+] Less [-]Uptake and adverse effects of polyethylene terephthalate microplastics fibers on terrestrial snails (Achatina fulica) after soil exposure
2019
Song, Yang | Cao, Chengjin | Qiu, Rong | Hu, Jiani | Liu, Mengting | Lu, Shibo | Shi, Huahong | Susman, Kathleen M. | He, Defu
Recent studies have demonstrated the occurrence of microplastic fibers (MFs) in soil environments. To determine whether MFs are harmful for soil biota, we evaluated toxic effects on terrestrial snails (Achatina fulica) after 28 d exposure to polyethylene terephthalate MFs at concentrations of 0.01–0.71 g kg−1 (dry soil weight). Digestion kinetics experiments on 24 snails showed that MFs can be ingested and excreted within 48 h. We found the appearance of cracks and deterioration on the surface of MFs after depuration by the digestive system. Prolonged exposure to 40 snails showed that 0.14–0.71 g kg−1 MFs caused an average reduction of 24.7–34.9% food intake and 46.6–69.7% excretion. 0.71 g kg−1 MFs induced significant villi damage in the gastrointestinal walls of 40% snails, but did not influence the histology of the liver and kidney. Moreover, 0.71 g kg−1 MFs exposure reduced glutathione peroxidase (59.3 ± 13.8%) and total antioxidant capacity (36.7 ± 8.5%), but elevated malondialdehyde level (58.0 ± 6.4%) in the liver, which indicates oxidative stress is involved in the toxic mechanism. Our results suggest that MFs have adverse impacts on the fitness of soil organisms, and highlight the ecological risks of microplastic pollution in terrestrial ecosystems.
Show more [+] Less [-]Physiological and biochemical responses to aluminum-induced oxidative stress in two cyanobacterial species
2019
Hamed, Seham M. | Hassan, Sherif H. | Selim, Samy | Kumar, Amit | Khalaf, Sameh M.H. | Wadaan, Mohammed A.M. | Hozzein, Wael N. | AbdElgawad, Hamada
Phycoremediation technologies significantly contribute to solving serious problems induced by heavy metals accumulation in the aquatic systems. Here we studied the mechanisms underlying Al stress tolerance in two diazotrophic cyanobacterial species, to identify suitable species for Al phycoremediation. Al uptake as well as the physiological and biochemical responses of Anabaena laxa and Nostoc muscorum to 7 days Al exposure at two different concentrations i.e., mild (100 μM) and high dose (200 μM), were investigated. Our results revealed that A. laxa accumulated more Al, and it could acclimatize to long-term exposure of Al stress. Al induced a dose-dependent decrease in photosynthesis and its related parameters e.g., chlorophyll content (Chl a), phosphoenolpyruvate carboxylase (PEPC) and Ribulose‒1,5‒bisphosphate carboxylase/oxygenase (RuBisCo) activities. The affect was less pronounced in A. laxa than N. muscorum. Moreover, Al stress significantly increased cellular membrane damage as indicated by induced H₂O₂, lipid peroxidation, protein oxidation, and NADPH oxidase activity. However, these increases were lower in A. laxa compared to N. muscorum. To mitigate the impact of Al stress, A. laxa induced its antioxidant defense system by increasing polyphenols, flavonoids, tocopherols and glutathione levels as well as peroxidase (POX), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GPX) enzymes activities. On the other hand, the antioxidant increases in N. muscorum were only limited to ascorbate (ASC) cycle. Overall, high biosorption/uptake capacity and efficient antioxidant defense system of A. laxa recommend its feasibility in the treatment of Al contaminated waters/soils.
Show more [+] Less [-]Blueberry anthocyanin alleviate perfluorooctanoic acid-induced toxicity in planarian (Dugesia japonica) by regulating oxidative stress biomarkers, ATP contents, DNA methylation and mRNA expression
2019
Zhang, Jianyong | Wang, Bin | Zhao, Bosheng | Li, Yanqing | Zhao, Xiuyun | Yuan, Zuoqing
Blueberry anthocyanin (BA) have strong health benefits as an active natural antioxidant and perfluorooctanoic acid (PFOA) can result in oxidative stress in animals. In our study, the protective effects of BA against stress induced by PFOA was investigated in the planarian Dugesia japonica using oxidative stress biomarkers, ATP contents, ATPase activity, DNA methylation and mRNA expression. PFOA exposure could resulted in malondialdehyde production. At the same time, treatment with BA decreased the production of malondialdehyde in BA-exposed and co-treatment planarians. PFOA caused activities increase in glutathione peroxidase (GPx), glutathione S-transferase (GST) and activities decrease in glutathione reductase (GR). PFOA exposure decreased the GSH and ATP contents. Additionally, it increased the GSSG contents and ATPase activity. BA administration increased the activities of GPx, GST and GR in BA and co-treatment planarians. Meanwhile BA maintained the contents of ATP, ATPase activity, GSH and GSSG by alleviating PFOA toxicity. Moreover, PFOA and BA increased the contents of 5-methylcytosine and decreased 5-hydroxymethylcytosine in all group. In addition, PFOA and BA treated planarians significantly altered the expression of genes associated with above biochemical parameters. The results showed that the mRNA expression of gpx, Djgst, gr, Djnak and dnmt1 were significantly elevated in all groups. Alterations in the mRNA expression levels indicated a stress response to PFOA exposure and anthocyanin protection. These alterations regulated biomarkers of oxidative stress, energy metabolism and DNA methylation levels in planarians. These results indicate that BA attenuated PFOA-induced oxidative stress, energy metabolism, DNA methylation and gene expression disorders.
Show more [+] Less [-]Marine contamination and cytogenotoxic effects of fluoxetine in the tropical brown mussel Perna perna
2019
Cortez, Fernando Sanzi | Souza, Lorena da Silva | Guimarães, Luciana Lopes | Pusceddu, Fabio Hermes | Maranho, Luciane Alves | Fontes, Mayana Karoline | Moreno, Beatriz Barbosa | Nobre, Caio Rodrigues | Abessa, Denis Moledo de Souza | Cesar, Augusto | Pereira, Camilo Dias Seabra
Concerns are growing about the presence of fluoxetine (FLX) in environmental matrices, as well as its harmful effects on non-target organisms. FLX in aquatic ecosystems has been detected in a range varying from pg/L to ng/L, while adverse effects have been reported in several organisms inhabiting freshwater and marine environments. The present study quantifies FLX concentrations in seawater samples from Santos Bay, Brazil and assesses metabolic responses and sublethal effects on the tropical brown mussel Perna perna. Levels of ethoxyresorufin‑O‑deethylase, dibenzylfluorescein dealkylase, glutathione S-transferase, glutathione peroxidase, cholinesterase, lipoperoxidation, and DNA damage were assessed in the gills and digestive gland of these animals, and lysosomal membrane stability was also assessed in hemocytes. FLX altered phase I and II enzyme activities, caused cytogenotoxic effects, and negatively impacted the overall health of mussels exposed to environmentally relevant concentrations. These findings contribute to characterize the risks of introducing this drug into the marine environment.
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