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Differential mitochondrial dysregulation by exposure to individual organochlorine pesticides (OCPs) and their mixture in zebrafish embryos
2021
Lee, Hyojin | Ko, Eun | Shin, Sooim | Choi, Moonsung | Kim, Ki-Tae
Organochlorine pesticides (OCPs) have been reported to cause mitochondrial dysfunction. However, most studies reported its mitochondrial toxicity with respect to a single form, which is far from the environmentally relevant conditions. In this study, we exposed zebrafish embryos to five OCPs: chlordane, heptachlor, p,p’-dichlorodiphenyltrichloroethane (p,p’-DDT), β-hexachlorocyclohexane (β-HCH), and hexachlorobenzene (HCB), as well as an equal ratio mixture of these OCPs. We evaluated mitochondrial function, including oxygen consumption, the activity of mitochondrial complexes, antioxidant reactions, and expression of genes involved in mitochondrial metabolism. Oxygen consumption rate was reduced by exposure to chlordane, and β-HCH, linking to the increased activity of specific mitochondrial complex I and III, and decreased GSH level. We found that these mitochondrial dysfunctions were more significant in the exposure to the OCP mixture than the individual OCPs. On the mRNA transcription level, the individual OCPs mainly dysregulated the metabolic cycle (i.e., cs and acadm), whereas the OCP mixture disrupted the genes related to mitochondrial oxidative phosphorylation (i.e., sdha). Consequently, we demonstrate that the OCP mixture disrupts mitochondrial metabolism by a different molecular mechanism than the individual OCPs, which warrants further study to evaluate mitochondrial dysregulation by chronic exposure to the OCP mixture.
Показать больше [+] Меньше [-]Sublethal effects of chlorantraniliprole on Paederus fuscipes (Staphylinidae: Coleoptera), a general predator in paddle field
2021
Mūsá K̲h̲ān̲, Muḥammad | Hafeez, Muhammad | Elgizawy, Karam | Wang, Hanyu | Zhao, Jing | Cai, Wanlun | Ma, Weihua | Hua, Hongxia
Paederus fuscipes is a general predator in rice fields and a non-target organism of chlorantraniliprole, an effective insecticide for insect-pest control in paddy fields. Pesticide hazards to non-target organisms have been a growing global problem for decades. This study was designed to evaluate the toxicity of chlorantraniliprole at lethal and sublethal levels against P. fuscipes larvae and adults. The LC₅₀ of chlorantraniliprole against P. fuscipes adults and larvae were respectively 535.49 and 111.24 mg a.i. L⁻¹, which is higher than the dosage recommended for use in the field (59.38 mg a.i. L⁻¹), but the LC₃₀ and LC₁₀ for larvae are lower than the recommended field dose which showed that the sublethal effects on immature stages are inevitable. Treatment at larval stage with LC₃₀ of chlorantraniliprole significantly elongated the pre-imaginal developmental and pre-oviposition periods. Also, adults exposed directly to chlorantraniliprole oviposited significantly less number of eggs in both LC₁₀ and LC₃₀ treatments. Furthermore, the larval predation efficiency and female bodyweight were also reduced due to exposure to sublethal doses. Meanwhile, the activities of antioxidant (SOD, POD and CAT) and detoxification (P450, AChE and GST) enzymes were also significantly affected by the exposure to these sublethal concentrations. These findings showed that sublethal doses of chlorantraniliprole adversely influenced P. fuscipes development and physiology, and therefore its use as part of integrative pest management should be given further considerations.
Показать больше [+] Меньше [-]Application of the in vivo oxidative stress reporter Hmox1 as mechanistic biomarker of arsenic toxicity
2021
Inesta-Vaquera, Francisco | Navasumrit, Panida | Henderson, Colin J. | Frangova, Tanya G. | Honda, Tadashi | Dinkova-Kostova, Albena T. | Ruchirawat, Mathuros | Wolf, C Roland
Inorganic arsenic (iAs) is a naturally occurring metalloid present in drinking water and polluted air exposing millions of people globally. Epidemiological studies have linked iAs exposure to the development of numerous diseases including cognitive impairment, cardiovascular failure and cancer. Despite intense research, an effective therapy for chronic arsenicosis has yet to be developed. Laboratory studies have been of great benefit in establishing the pathways involved in iAs toxicity and providing insights into its mechanism of action. However, the in vivo analysis of arsenic toxicity mechanisms has been difficult by the lack of reliable in vivo biomarkers of iAs’s effects. To address this issue we have applied the use of our recently developed stress reporter models to study iAs toxicity. The reporter mice Hmox1 (oxidative stress/inflammation; HOTT) and p21 (DNA damage) were exposed to iAs at acute and chronic, environmentally relevant, doses. We observed induction of the oxidative stress reporters in several cell types and tissues, which was largely dependent on the activation of transcription factor NRF2. We propose that our HOTT reporter model can be used as a surrogate biomarker of iAs-induced oxidative stress, and it constitutes a first-in-class platform to develop treatments aimed to counteract the role of oxidative stress in arsenicosis. Indeed, in a proof of concept experiment, the HOTT reporter mice were able to predict the therapeutic utility of the antioxidant N-acetyl cysteine in the prevention of iAs associated toxicity.
Показать больше [+] Меньше [-]Environmentally relevant concentration of sulfamethoxazole-induced oxidative stress-cascaded damages in the intestine of grass carp and the therapeutic application of exogenous lycopene
2021
Wang, Yu | Zhao, Hongjing | Liu, Yachen | Li, Jingyan | Nie, Xiaopan | Huang, Puyi | Xing, Mingwei
Due to the unreasonable use and discharge of the aquaculture industry, over standard of the antibiotics has been frequent in different types of water environments, causing adverse effects on aquatic organisms. Lycopene (LYC) is an esculent carotenoid, which is considered to be a strong antioxidant. This study was designed to explore the therapeutic effect of LYC on antibiotic (sulfamethoxazole (SMZ)) induced intestinal injury in grass carp Ctenopharyngodon idella. The 120 carps (the control, LYC, SMZ, and co-administration groups) were treated for 30 days. We found that treatment with LYC significantly suppressed SMZ-induced intestinal epithelial cell damage and tight junction protein destruction through histopathological observation, transmission electron microscopy and detection of related genes (Claudin-1/3/4, Occludin and zonula occludens (ZO)-1/2). Furthermore, LYC mitigated SMZ-induced dysregulation of oxidative stress markers, including elevated malondialdehyde (MDA) levels, and consumed super oxide dimutese (SOD), catalase (CAT) activities and glutathione (GSH) content. In the same treatment, LYC reduced inflammation and apoptosis by a detectable change in pro-inflammatory factors (tumor necrosis factor-alpha (TNF-β), interleukin (IL)-1β, IL-6 and IL-8), anti-inflammatory factors (transforming growth factor-beta (TGF-β) and IL-10) and pro-apoptosis related genes (p53, p53 upregulated modulator of apoptosis (PUMA), Bax/Bcl-2 ratio, caspase-3/9). In addition, activation of autophagy (as indicated by increased autophagy-related genes through AMPK/ATK/MTOR signaling pathway) under the stress of SMZ was also dropped back to the original levels by LYC co-administration. Collectively, our findings identified that LYC can serve as a protectant agent against SMZ-induced intestinal injury.
Показать больше [+] Меньше [-]Pharmacological inhibition of PAI-1 alleviates cardiopulmonary pathologies induced by exposure to air pollutants PM2.5
2021
Ghosh, Asish K. | Soberanes, Saul | Lux, Elizabeth | Shang, Meng | Aillon, Raul Piseaux | Eren, Mesut | Budinger, G.R Scott | Miyata, Toshio | Vaughan, Douglas E.
Numerous studies have established that acute or chronic exposure to environmental pollutants like particulate matter (PM) leads to the development of accelerated aging related pathologies including pulmonary and cardiovascular diseases, and thus air pollution is one of the major global threats to human health. Air pollutant particulate matter 2.5 (PM₂.₅)-induced cellular dysfunction impairs tissue homeostasis and causes vascular and cardiopulmonary damage. To test a hypothesis that elevated plasminogen activator inhibitor-1 (PAI-1) levels play a pivotal role in air pollutant-induced cardiopulmonary pathologies, we examined the efficacy of a drug-like novel inhibitor of PAI-1, TM5614, in treating PM₂.₅-induced vascular and cardiopulmonary pathologies. Results from biochemical, histological, and immunohistochemical studies revealed that PM₂.₅ increases the circulating levels of PAI-1 and thrombin and that TM5614 treatment completely abrogates these effects in plasma. PM₂.₅ significantly augments the levels of pro-inflammatory cytokine interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF), and this also can be reversed by TM5614, indicating its efficacy in amelioration of PM₂.₅-induced increases in inflammatory and pro-thrombotic factors. TM5614 reduces PM₂.₅-induced increased levels of inflammatory markers cluster of differentiation 107 b (Mac3) and phospho-signal transducer and activator of transcription-3 (pSTAT3), adhesion molecule vascular cell adhesion molecule 1 (VCAM1), and apoptotic marker cleaved caspase 3. Longer exposure to PM₂.₅ induces pulmonary and cardiac thrombosis, but TM5614 significantly ameliorates PM₂.₅-induced vascular thrombosis. TM5614 also reduces PM₂.₅-induced increased blood pressure and heart weight. In vitro cell culture studies revealed that PM₂.₅ induces the levels of PAI-1, type I collagen, fibronectin (Millipore), and sterol regulatory element binding protein-1 and 2 (SREBP-1 and SREBP-2), transcription factors that mediate profibrogenic signaling, in cardiac fibroblasts. TM5614 abrogated that stimulation, indicating that it may block PM₂.₅-induced PAI-1 and profibrogenic signaling through suppression of SREBP-1 and 2. Furthermore, TM5614 blocked PM₂.₅-mediated suppression of nuclear factor erythroid related factor 2 (Nrf2), a major antioxidant regulator, in cardiac fibroblasts. Pharmacological inhibition of PAI-1 with TM5614 is a promising therapeutic approach to control air pollutant PM₂.₅-induced cardiopulmonary and vascular pathologies.
Показать больше [+] Меньше [-]Green synthesis, characterization and applications of silver nanoparticle mediated by the aqueous extract of red onion peel
2021
Tan Sian Hui Abdullah, Hannan Safiyyah | Aqlili Riana Mohd Asseri, Siti Nur | Khursyiah Wan Mohamad, Wan Nurul | Kan, Su-Yin | Azmi, Alyza Azzura | Yong Julius, Fu Siong | Chia, Poh Wai
This manuscript describes the reuse of biowaste for the biosynthesis of silver nanoparticles (AgNPs) and their applications. In particular, we hypothesized that the phytochemicals in the onion peels could act as reductant for silver nanoparticles syntheses. AgNO₃ solution (1 mmol) was added dropwise to an aqueous solution of onion peel extract in 3:7 ratio. The reaction mixture was subjected to heating at 90 °C for about 30 min. During the synthesis of the AgNPs, the change of the colour of solution was observed. The AgNPs solution was centrifuged to obtain the two layers, which consists of clear solution and solid layers at 12000 rpm for 30 min. The precipitate was filtered and was re-dispersed in deionised water (25 mL). The solution was centrifuged again to obtain the purified AgNPs. Subsequently, this solution was freeze dried for 48 h to afford the powdered AgNPs. In this work, the structure of the AgNPs were synthesized in spherical shape, with an average size of 12.5 nm observed in the Transmission electron microscopy (TEM) analysis. For catalytic application, the synthesized AgNPs could be applied as green catalyst to promote Knoevenagel and Hantzsch reactions. In most cases, the desired products were obtained in satisfactory yields. In addition, the AgNPs were found to be recyclable for the subsequent reactions. After five successive runs, the average isolated yields for both transformations were recorded to be 91% (Knoevenagel condensation) and 94% (Hantzsch reaction), which indicated that the existing AgNPs could apply as green catalyst in the field of organic synthesis. Furthermore, the AgNPs also showed satisfactory result in antioxidant activity. The current results indicate that the AgNPs can act as alternative antioxidant agent and green catalyst in mediating organic transformations.
Показать больше [+] Меньше [-]Eugenol mitigated acute lung but not spermatic toxicity of C60 fullerene emulsion in mice
2021
Pinheiro, Felipe Gomes | Moreira-Gomes, Maria Diana | Machado, Mariana Nascimento | Almeida, Tailane dos Santos | Barboza, Priscila da Penha Apolinário | Silva Oliveira, Luis Felipe | Ávila Cavalcante, Francisco Sales | Leal-Cardoso, José Henrique | Fortunato, Rodrigo Soares | Zin, Walter Araujo
C₆₀ fullerene (C₆₀) is a nano-pollutant that can damage the respiratory system. Eugenol exhibits significant anti-inflammatory and antioxidant properties. We aimed to investigate the time course of C₆₀ emulsion-induced pulmonary and spermatic harms, as well as the effect of eugenol on C₆₀ emulsion toxicity. The first group of mice (protocol 1) received intratracheally C₆₀ emulsion (1.0 mg/kg BW) or vehicle and were tested at 12, 24, 72 and 96 h (F groups) thereafter. The second group of mice (protocol 2) received intratracheally C₆₀ emulsion or vehicle, 1 h later were gavaged with eugenol (150 mg/kg) or vehicle, and experiments were done 24 h after instillation. Lung mechanics, morphology, redox markers, cytokines and epididymal spermatozoa were analyzed. Protocol 1: Tissue damping (G) and elastance (H) were significantly higher in F24 than in others groups, except for H in F72. Morphological and inflammatory parameters were worst at 24 h and subsequently declined until 96 h, whereas redox and spermatic parameters worsened over the whole period. Eugenol eliminated the increase in G, H, cellularity, and cytokines, attenuated oxidative stress induced by C60 exposure, but had no effect on sperm. Hence, exposure to C₆₀ emulsion deteriorated lung morphofunctional, redox and inflammatory characteristics and increased the risk of infertility. Furthermore, eugenol avoided those changes, but did not prevent sperm damage.
Показать больше [+] Меньше [-]Impacts of oxalic acid-activated phosphate rock and root-induced changes on Pb bioavailability in the rhizosphere and its distribution in mung bean plant
2021
Rasool, Bilal | ur-Rahman, Mahmood | Adnan Ramzani, Pia Muhammad | Zubair, Muhammad | Khan, Muhammad Asaf | Lewińska, Karolina | Turan, Veysel | Karczewska, Anna | Khan, Shahbaz Ali | Farhad, Muniba | Tauqeer, Hafiz Muhammad | Iqbal, Muhammad
Rhizosphere acidification in leguminous plants can release P from the dissolution of phosphate compounds which can reduce Pb bioavailability to them via the formation of insoluble Pb compounds in their rhizosphere. A soil polluted from Pb-acid batteries effluent (SPBE), having total Pb = 639 mg kg⁻¹, was amended with six different rates (0, 0.5, 1, 2, 4 and 6%) of oxalic acid-activated phosphate rock (OAPR) and their effects on pH, available P and bioavailable Pb concentrations in the rhizosphere and bulk soils of mung bean plant were evaluated. Furthermore, the effects of these variant OAPR rates on Pb concentrations in plant parts, bioaccumulation factor (BAF) and translocation factor (TF) for Pb in grain and traits like productivity, the activities of antioxidant enzymes, and grain biochemistry were investigated. Results revealed that increasing rates of OAPR significantly increased pH values and available P while decreased bioavailable Pb concentrations in the rhizosphere over control. The highest dissolution of P in the rhizosphere was with 4 and 6% OAPR rates. As a result, the formation of insoluble Pb compounds affected on reduced Pb concentrations in shoots, roots, and grain in addition to lower grain BAF and TF values for Pb over control. Likewise, the highest plant productivity, improved grain biochemistry, high Ca and Mg concentrations, least oxidative stress, and enhanced soil alkaline phosphatase activity were found with 4 and 6% OAPR rates. The OAPR 4% rate is suggested for reducing grain Pb concentration, cell oxidative injury, and improving grain biochemistry in mung bean.
Показать больше [+] Меньше [-]Canidin-3-glucoside prevents nano-plastics induced toxicity via activating autophagy and promoting discharge
2021
Chen, Wen | Chu, Qiang | Ye, Xiang | Sun, Yuhao | Liu, Yangyang | Jia, Ruoyi | Li, Yonglu | Tu, Pengcheng | Pan, Jijiong | Yu, Ting | Chen, Chuan | Zheng, Xiaodong
Increasing attention has been brought to microplastics pollution recently, while emerging evidences indicate that nano-plastics degraded from microplastics are more of research significance owing to stronger toxicity. However, there is little study focused on the prevention of nano-plastics induced toxicity until now. Canidin-3-glucoside (C3G), a natural anthocyanin proved to possess multiple functions like antioxidant and intestinal tissue protection. Thus, we proposed whether C3G could act as a molecular weapon against nano-plastics induced toxicity. In Caco2 cell and Caenorhabditis elegans (C. elegans) models, we found that polystyrene (PS) nano-plastics exposure resulted in physiological toxicity and oxidative damage, which could be restored by C3G. More significantly in Caco2 cells, we observed that autophagy was activated via Sirt1-Foxo1 signaling pathway to attenuate PS induced toxicity after C3G intervention and further verified by adding autophagy inhibitor 3-Methyladenine (3-MA). Meanwhile, PS co-localization with lysosomes was observed, indicating the encapsulation and degradation of PS. In C. elegans, by detecting LGG-1/LC3 expression in GFP-targeted LGG-1 report gene (LGG-1:GFP) labeled transgenic DA2123 strain, the co-localization of LGG-1:GFP with PS was found as well, means that autophagy is involved in C3G’s beneficial effects. Furthermore, we were surprised to find that C3G could promote the discharge of PS from N2 nematodes, which reduces PS toxicity more directly.
Показать больше [+] Меньше [-]First evidence of the protective role of melatonin in counteracting cadmium toxicity in the rat ovary via the mTOR pathway
2021
Kechiche, Safa | Venditti, Massimo | Knani, Latifa | Jabłońska, Karolina | Dziegiel, Piotr | Messaoudi, Imed | Reiter, Russel J. | Minucci, Sergio
Herein, the first evidence of the ability of melatonin (MLT) to counteract cadmium (Cd) toxic effects on the rat ovary is reported. Cd treatment, enhancing oxidative stress, provoked clear morphological, histological and biomolecular alterations, i.e. in the estrous cycle duration, in the ovarian and serum E₂ concentration other than in the steroidogenic and folliculogenic genes expression. Results demonstrated that the use of MLT, in combination with Cd, avoided the changes, strongly suggesting that it is an efficient antioxidant for preventing oxidative stress in the rat ovary. Moreover, to explore the underlying mechanism involved, at molecular level, in the effects of Cd-MLT interaction, the study focused on the mTOR and ERK1/2 pathways. Interestingly, data showed that Cd influenced the phosphorylation status of mTOR, of its downstream effectors and of ERK1/2, inducing autophagy and apoptosis, while cotreatment with MLT nullified these changes. This work highlights the beneficial role exerted by MLT in preventing Cd-induced toxicity in the rat ovary, encouraging further studies to confirm its action on human ovarian health with the aim to use this indolamine to ameliorate oocyte quality in women with fertility disorders.
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