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Mechanism of thorium-nitrate and thorium-dioxide induced cytotoxicity in normal human lung epithelial cells (WI26): Role of oxidative stress, HSPs and DNA damage
2021
Das, Sourav Kumar | Ali, Manjoor | Shetake, Neena G. | Dumpala, Rama Mohan R. | Pandey, Badri N. | Kumar, Amit
Inhalation represents the most prevalent route of exposure with Thorium-232 compounds (Th-nitrate/Th-dioxide)/Th-containing dust in real occupational scenario. The present study investigated the mechanism of Th response in normal human alveolar epithelial cells (WI26), exposed to Th-nitrate or colloidal Th-dioxide (1–100 μg/ml, 24–72 h). Assessment in terms of changes in cell morphology, cell proliferation (cell count), plasma membrane integrity (lactate dehydrogenase leakage) and mitochondrial metabolic activity (MTT reduction) showed that Th-dioxide was quantitatively more deleterious than Th-nitrate to WI26 cells. TEM and immunofluorescence analysis suggested that Th-dioxide followed a clathrin/caveolin-mediated endocytosis, however, membrane perforation/non-endocytosis seemed to be the mode of Th internalization in cells exposed to Th-nitrate. Th-estimation by ICP-MS showed significantly higher uptake of Th in cells treated with Th-dioxide than with Th-nitrate at a given concentration. Both Th-dioxide and nitrate were found to increase the level of reactive oxygen species, which seemed to be responsible for lipid peroxidation, alteration in mitochondrial membrane potential and DNA-damage. Amongst HSPs, the protein levels of HSP70 and HSP90 were affected differentially by Th-nitrate/dioxide. Specific inhibitors of ATM (KU55933) or HSP90 (17AAG) were found to increase the Th- cytotoxicity suggesting prosurvival role of these signaling molecules in rescuing the cells from Th-toxicity.
Show more [+] Less [-]Potamopyrgus antipodarum has the potential to detect effects from various land use activities on a freshwater ecosystem
2021
Subba, Maita | Keough, Michael J. | Kellar, Claudette | Roth, Sara Long | Miranda, Ana | Pettigrove, Vincent J.
Identifying risks to ecosystems from contaminants needs a diversity of bioindicators, to understand the effects of these contaminants on a range of taxa. Molluscs are an ideal bioindicator because they are one of the largest phyla with extremely high ecological and economic importance. The aim of this study was to evaluate if laboratory bred Potamopyrgus antipodarum has the potential to show the impact of contaminants from various land use activities and degree of pollution on a freshwater ecosystem. We assessed the impact of contaminants arising from runoff and direct discharges in Merri Creek by measuring organism level responses (survival, growth, and reproduction), and sub-organism level responses (glutathione S-transferase (GST) activity, lipid peroxidation (LPO) activity and catalase (CAT) activity) in snails after 28-d of deployment at nine sites in Merri Creek and one site in Cardinia Creek. In Merri Creek, the top two sites were reference sites (with low impact from human activities), while the rest were impact sites (impacted by various anthropogenic land uses). Cardinia Creek (an additional reference site) had lower human activity. High concentrations of heavy metals, nutrients, and/or synthetic pyrethroids (bifenthrin) dominated these sites, which are likely to have contributed towards the negative responses observed in the snails. There was little influence from environmental conditions and site location on the endpoints because we found a similar response at an additional reference site compared to the reference sites in Merri Creek. At the organism level, reproduction increased and/or reduced, while CAT was affected at the sub-organism level. Potamopyrgus antipodarum has the potential to be a sensitive bioindicator for Australian conditions because the snails responded to varying concentrations of contaminants across different land use activities and showed similar sensitivity to P. antipodarum found in other regions of the globe and other bioindicators.
Show more [+] Less [-]Biomarkers-based assessment of triclosan toxicity in aquatic environment: A mechanistic review
2021
Kumar, Saurav | Paul, Tapas | Shukla, S.P. | Kundan Kumar, | Karmakar, Sutanu | Bera, Kuntal Krishna | Bhushan kumar, Chandra
Triclosan (TCS), an emergent pollutant, is raising a global concern due to its toxic effects on organisms and aquatic ecosystems. The non-availability of proven treatment technologies for TCS remediation is the central issue stressing thorough research on understanding the underlying mechanisms of toxicity and assessing vital biomarkers in the aquatic organism for practical monitoring purposes. Given the unprecedented circumstances during COVID 19 pandemic, a several-fold higher discharge of TCS in the aquatic ecosystems cannot be considered a remote possibility. Therefore, identifying potential biomarkers for assessing chronic effects of TCS are prerequisites for addressing the issues related to its ecological impact and its monitoring in the future. It is the first holistic review on highlighting the biomarkers of TCS toxicity based on a comprehensive review of available literature about the biomarkers related to cytotoxicity, genotoxicity, hematological, alterations of gene expression, and metabolic profiling. This review establishes that biomarkers at the subcellular level such as oxidative stress, lipid peroxidation, neurotoxicity, and metabolic enzymes can be used to evaluate the cytotoxic effect of TCS in future investigations. Micronuclei frequency and % DNA damage proved to be reliable biomarkers for genotoxic effects of TCS in fishes and other aquatic organisms. Alteration of gene expression and metabolic profiling in different organs provides a better insight into mechanisms underlying the biocide's toxicity. In the concluding part of the review, the present status of knowledge about mechanisms of antimicrobial resistance of TCS and its relevance in understanding the toxicity is also discussed referring to the relevant reports on microorganisms.
Show more [+] Less [-]Biochar mitigates arsenic-induced human health risks and phytotoxicity in quinoa under saline conditions by modulating ionic and oxidative stress responses
2021
Shabbir, Arslan | Saqib, Muhammad | Murtaza, Ghulam | Abbas, Ghulam | Imran, Muhammad | Rizwan, Muhammad | Naeem, Muhammad Asif | Ali, Shafaqat | Rashad Javeed, Hafiz Muhammad
Arsenic (As) is a toxic metalloid and its widespread contamination in agricultural soils along with soil salinization has become a serious concern for human health and food security. In the present study, the effect of cotton shell biochar (CSBC) in decreasing As-induced phytotoxicity and human health risks in quinoa (Chenopodium quinoa Willd.) grown on As-spiked saline and non-saline soils was evaluated. Quinoa plants were grown on As contaminated (0, 15 and 30 mg kg⁻¹) saline and non-saline soils amended with 0, 1 and 2% CSBC. Results showed that plant growth, grain yield, stomatal conductance and chlorophyll contents of quinoa showed more decline on As contaminated saline soil than non-saline soil. The application of 2% CSBC particularly enhanced plant growth, leaf relative water contents, stomatal conductance, pigment contents and limited the uptake of As and Na as compared to soil without CSBC. Salinity in combination with As trigged the production of H₂O₂ and caused lipid peroxidation of cell membranes. Biochar ameliorated the oxidative stress by increasing the activities of antioxidant enzymes (SOD, POD, CAT). Carcinogenic and non-carcinogenic human health risks were greatly decreased in the presence of biochar. Application of 2% CSBC showed promising results in reducing human health risks and As toxicity in quinoa grown on As contaminated non-saline and saline soils. Further research is needed to evaluate the role of biochar in minimizing As accumulation in other crops on normal as well as salt affected soils under field conditions.
Show more [+] Less [-]Serum concentrations of organochlorine pesticides, biomarkers of oxidative stress, and risk of breast cancer
2021
Miao, Yu | Rong, Mao | Li, Min | He, Heng | Zhang, Li | Zhang, Shanshan | Liu, Chong | Zhu, Ying | Deng, Yan-Ling | Chen, Pan-Pan | Zeng, Jia-Yue | Zhong, Rong | Mei, Su-Rong | Miao, Xiao-Ping | Zeng, Qiang
Studies have documented that exposure to organochlorine pesticides (OCPs) is linked with breast cancer, but the underlying biological mechanisms are still unknown. This study included 313 women diagnosed with breast cancer and 313 controls in Wuhan, China, and measured 18 OCPs in serum and 3 oxidative stress biomarkers in urine. Multivariable adjusted regression models were used to evaluate the associations among OCPs, oxidative stress biomarkers, and breast cancer. The mediating effect of oxidative stress was assessed by mediation analysis. We observed that most OCPs were positively associated with risk of breast cancer (all FDR-P values < 0.05 or 0.10). Moreover, we found that p,p'-DDT, p,p'-DDD, dieldrin, heptachlor, and heptachlor epoxide were positively associated with 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-iso-prostaglandin F₂α (8-isoPGF₂α), which in turn were positively associated with risk of breast cancer. Mediation analysis indicated that HNE-MA and 8-isoPGF₂ɑ mediated the positive associations between these OCPs and risk of breast cancer, with mediating proportion ranging from 6.23% to 19.9%. Our results suggest that lipid peroxidation may mediate the positive associations between OCP exposures and risk of breast cancer.
Show more [+] Less [-]Sulfur deficiency exacerbates phytotoxicity and residues of imidacloprid through suppression of thiol-dependent detoxification in lettuce seedlings
2021
Zhang, Nan | Huang, Lin | Zhang, Yuxue | Liu, Lijuan | Sun, Chengliang | Lin, Xianyong
Sulfur, an essential macronutrient, plays important roles in plant development and stress mitigation. Sulfur deficiency, a common problem in agricultural soils, may disturb plant stress resistance and xenobiotic detoxification. In the present study, the function and mechanism of limited sulfur nutrition on the residues and phtotoxicity of imidacloprid were investigated in lettuce plants. Sulfur deficiency significantly increased imidacloprid accumulation in lettuce tissues, exacerbated imidacloprid biological toxicity by enhancing the accumulation of toxic metabolites, like imidacloprid-olefin. Simultaneously, imidacloprid-induced detoxification enzymes including cytochromes P450, glutathione S-transferases (GSTs) and glycosyltransferases were inhibited under limited sulfur supply. On the other hand, sulfur deficiency further enhanced the generation of reactive oxygen species and exacerbated lipid peroxidation in lettuce tissues. Sulfur deficiency mainly reduced the abundance of thiol groups, which are essential redox modulators as well as xenobiotic conjugators, and significantly inhibited GSTs expression. These results clearly suggested that sulfur deficiency inhibited the synthesis of sulfur-containing compounds, leading to increased accumulation of pesticide residues and toxic metabolites as well as reduced detoxification capacity, consequently leading to oxidative damage to plants. Therefore, moderate sulfur supply in regions where neonicotinoid insecticides are intensively and indiscriminately used may be an efficient strategy to reduce pesticide residues and the potential risk to ecosystem.
Show more [+] Less [-]Urinary metabolites of multiple volatile organic compounds among general population in Wuhan, central China: Inter-day reproducibility, seasonal difference, and their associations with oxidative stress biomarkers
2021
Qian, Xi | Wan, Yanjian | Wang, Aizhen | Xia, Wei | Yang, Zong | He, Zhenyu | Xu, Shunqing
General population are concurrently and extensively exposed to many volatile organic compounds (VOCs), including some Group 1 human carcinogens, such as 1,3-butadiene. However, only a few studies assessed internal exposure levels of VOCs; particularly, very limited studies have examined associations between the urinary concentrations of multiple VOC metabolites (mVOCs) and oxidative stress biomarkers (OSBs) among the general population. In this study, 21 mVOCs and three OSBs including 8-hydroxy-2′-deoxyguanosine (8-OHdG; for DNA), 8-hydroxyguanosine (8-OHG; for RNA), and 4-hydroxy nonenal mercapturic acid (HNEMA; for lipid) were measured in 406 urine samples collected from 128 healthy adults during autumn and winter of 2018 in Wuhan, central China, including repeated samples taken in 3 d from 75 volunteers. Inter-day reproducibility for most mVOCs was good to excellent; urinary concentrations of mVOCs in winter were generally higher than those in autumn. Risk assessment was conducted by calculating hazard quotients for the parent compounds, and the results suggested that acrolein, 1,3-butadiene, and cyanide should be considered as high-priority hazardous ones for management. After false-discovery adjustment, 16 of the studied mVOCs were positively associated with 8-OHdG and 8-OHG (β values ranged from 0.04 to 0.48), and four mVOCs were positively associated with HNEMA (β values ranged from 0.21 to 0.78). Weighted quantile sum regression analyses were used to assess associations of mVOC mixture and OSBs, and we found significantly positive associations between the mixture index and OSBs, among which the strongest mVOC contributors for the associations were 2-methylhippuric acid for both DNA (20%) and RNA (17%) oxidative damage, and trans,trans-muconic acid (50%) for lipid peroxidation. This study firstly reported good to excellent short-term reproducibility, seasonal difference in autumn and winter, and possible health risk in urinary concentrations of multiple mVOCs among the general population.
Show more [+] Less [-]Exposure to nanoparticles derived from diesel particulate filter equipped engine increases vulnerability to arrhythmia in rat hearts
2021
Rossi, Stefano | Buccarello, Andrea | Caffarra Malvezzi, Cristina | Pinelli, Silvana | Alinovi, Rossella | Guerrero Gerboles, Amparo | Rozzi, Giacomo | Leonardi, Fabio | Bollati, Valentina | De Palma, Giuseppe | Lagonegro, Paola | Rossi, F. (Francesca) | Lottici, Pier Paolo | Poli, Diana | Statello, Rosario | Macchi, Emilio | Miragoli, Michele
Air pollution is well recognized as a central player in cardiovascular disease. Exhaust particulate from diesel engines (DEP) is rich in nanoparticles and may contribute to the health effects of particulate matter in the environment. Moreover, diesel soot emitted by modern engines denotes defective surfaces alongside chemically-reactive sites increasing soot cytotoxicity. We recently demonstrated that engineered nanoparticles can cross the air/blood barrier and are capable to reach the heart. We hypothesize that DEP nanoparticles are pro-arrhythmogenic by direct interaction with cardiac cells. We evaluated the internalization kinetics and the effects of DEP, collected from Euro III (DEPe3, in the absence of Diesel Particulate Filter, DPF) and Euro IV (DEPe4, in the presence of DPF) engines, on alveolar and cardiac cell lines and on in situ rat hearts following DEP tracheal instillation. We observed significant differences in DEP size, metal and organic compositions derived from both engines. DEPe4 comprised ultrafine particles (<100 nm) and denoted a more pronounced toxicological outcome compared to DEPe3. In cardiomyocytes, particle internalization is fastened for DEPe4 compared to DEPe3. The in-vivo epicardial recording shows significant alteration of EGs parameters in both groups. However, the DEPe4-instilled group showed, compared to DEPe3, a significant increment of the effective refractory period, cardiac conduction velocity, and likelihood of arrhythmic events, with a significant increment of membrane lipid peroxidation but no increment in inflammation biomarkers. Our data suggest that DEPe4, possibly due to ultrafine nanoparticles, is rapidly internalized by cardiomyocytes resulting in an acute susceptibility to cardiac electrical disorder and arrhythmias that could accrue from cellular toxicity. Since the postulated transfer of nanoparticles from the lung to myocardial cells has not been investigated it remains open whether the effects on the cardiovascular function are the result of lung inflammatory reactions or due to particles that have reached the heart.
Show more [+] Less [-]Pyriproxyfen induces intracellular calcium overload and alters antioxidant defenses in Danio rerio testis that may influence ongoing spermatogenesis
2021
Staldoni de Oliveira, Vanessa | Gomes Castro, Allisson Jhonatan | Marins, Katiuska | Bittencourt Mendes, Ana Karla | Araújo Leite, Gabriel Adan | Zamoner, Ariane | Van Der Kraak, Glen | Mena Barreto Silva, Fátima Regina
We investigated the in vitro effects of pyriproxyfen on ionic balance in the testis of the zebrafish by measuring ⁴⁵Ca²⁺ influx. In vivo pyriproxyfen treatment was carried out to study oxidative stress, and conduct morphological analysis of the testis and liver. Whole testes were incubated in vitro with/without pyriproxyfen (10⁻¹², 10⁻⁹ or 10⁻⁶ M; 30 min) and ⁴⁵Ca²⁺ influx determined. To study pyriproxyfen’s mechanism of action, inhibitors/activators of ionic channels or pumps/exchangers, protein kinase inhibitors or a calcium chelator were added 15 min before the addition of ⁴⁵Ca²⁺ and pyriproxyfen. We evaluated the in vivo effects of 7 day exposure to waterborne pyriproxyfen (10⁻⁹ M) on reactive oxygen species (ROS) formation, lipid peroxidation, and reduced glutathione content (GSH), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and γ-glutamyltransferase (GGT) activity. Morphological analyses of the testis and liver were carried out after in vivo exposure of D. rerio to pyriproxyfen. Pyriproxyfen increased ⁴⁵Ca²⁺ influx by opening the voltage-dependent T-type channels (T-type VDCC), inhibiting sarco/endoplasmic reticulum ⁴⁵Ca²⁺-ATPase (SERCA) and the NCX exchanger (forward mode) and by mobilizing calcium from stores. The involvement of potassium channels and protein kinase C (PKC) was also demonstrated in pyriproxyfen-induced intracellular calcium elevation. In vivo pyriproxyfen treatment of D. rerio increased lipid peroxidation, decreased GSH content and increased GST activity in testes, in addition to increasing the number and size of spermatogonia cysts and inducing hepatocyte basophilia and dilation of blood vessels in the liver. The toxicity of pyriproxyfen is mediated by calcium overload, increased lipid peroxidation, and a diminished antioxidant capacity in the testis, due to GSH depletion, and altered spermatogenesis. The development of high basophilia in the liver suggests that pyriproxyfen may have estrogenic activity, possibly acting as an endocrine-disruptor. These findings indicate that these alterations may contribute to pyriproxyfen toxicity and spermatogenesis disruption.
Show more [+] Less [-]Isolated and combined effects of thermal stress and copper exposure on the trophic behavior and oxidative status of the reef-building coral Mussismilia harttii
2021
da Silva Fonseca, Juliana | Mies, Miguel | Paranhos, Alana | Taniguchi, Satie | Güth, Arthur Z. | Bícego, Márcia C. | Marques, Joseane Aparecida | Fernandes de Barros Marangoni, Laura | Bianchini, Adalto
Global warming and local disturbances such as pollution cause several impacts on coral reefs. Among them is the breakdown of the symbiosis between host corals and photosynthetic symbionts, which is often a consequence of oxidative stress. Therefore, we investigated if the combined effects of thermal stress and copper (Cu) exposure change the trophic behavior and oxidative status of the reef-building coral Mussismilia harttii. Coral fragments were exposed in a mesocosm system to three temperatures (25.0, 26.6 and 27.3 °C) and three Cu concentrations (2.9, 5.4 and 8.6 μg L⁻¹). Samples were collected after 4 and 12 days of exposure. We then (i) performed fatty acid analysis by gas chromatography-mass spectrometry to quantify changes in stearidonic acid and docosapentaenoic acid (autotrophy markers) and cis-gondoic acid (heterotrophy marker), and (ii) assessed the oxidative status of both host and symbiont through analyses of lipid peroxidation (LPO) and total antioxidant capacity (TAC). Our findings show that trophic behavior was predominantly autotrophic and remained unchanged under individual and combined stressors for both 4- and 12-day experiments; for the latter, however, there was an increase in the heterotrophy marker. Results also show that 4 days was not enough to trigger changes in LPO or TAC for both coral and symbiont. However, the 12-day experiment showed a reduction in symbiont LPO associated with thermal stress alone, and the combination of stressors increased their TAC. For the coral, the isolated effects of increase in Cu and temperature led to an increase in LPO. The effects of combined stressors on trophic behavior and oxidative status were not much different than those from the isolated effects of each stressor. These findings highlight that host and symbionts respond differently to stress and are relevant as they show the physiological response of individual holobiont compartments to both global and local stressors.
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