JOURNAL OF HAZARDOUS MATERIALS
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2020
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IF 9.038
Lanqiao Wang,Lanxi Wang,Xu Shi,Shiwen Xu
Excessive chlorpyrifos (CPF) in the environment causes toxicity to nontarget organisms by triggering oxidative stress. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) plays an important role in controlling apoptosis and necrosis by negatively regulating the phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) pathway. However, the effects of different concentrations of CPF on grass fish liver cell injury and the role of the ROS/PTEN/PI3K/AKT axis remain poorly understood. In this study, L8824 cells treated with different concentrations of CPF (0, 40, 60, or 80 μM) were used as the research object. The results showed that the median inhibitory concentration (IC50) was 112.226 μM. As the CPF concentrations increased, the ROS and MDA levels increased, and the T-AOC levels and SOD/GPx/GST activities decreased. As PTEN expression increased, PI3K/AKT, BCL-2, and Caspase-8 expression dramatically decreased. Conversely, RIPK1/RIPK3/MLKL and Bax/Cyt-c/Caspase-3 expression increased. Additionally, necroptosis increased in a dose-dependent manner, while apoptosis first increased and then decreased. In conclusion, our study showed that CPF could trigger oxidative stress and induce apoptosis and necroptosis in fish liver cells by regulating the ROS/PTEN/PI3K/AKT axis, and the type of damage induced was dose-dependent. These results are meaningful for toxicological studies of CPF and efforts to protect the ecosystem.
研究领域:
毒理学
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细胞生物学
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Junguo Ma,Penglin Zhu,Wenhua Wang,Xiaodan Zhang,Panliang Wang,Yousef Sultan,Yuanyuan Li,Weikai Ding,Xiaoyu Li
Chlorpyrifos (CPF) has been extensively used in the world and frequently found in natural environments, might cause a range of environmental issues and pose a health risk to aquatic species. However, investigation of its toxic effects on offspring after parental exposure has been neglected, especially for aquatic organisms such as fish. In the current study, the effects of chronic CPF exposure (3 and 60 μg/L) on adult zebrafish (F0) was investigated to determine its influence on adult reproductive capacity and offspring (F1 and F2). The results showed the existence of CPF both in F0 ovaries and F1 embryos and larvae, indicating that CPF could be transferred directly from the F0 adult fish to F1 offspring. After 90 d exposure, we observed that F0 female fish showed increased proportion of perinucleolar oocyte in the ovaries, decreased proportion of mature oocyte, and decreased egg production, but not in F1 adult. The transcriptomic analysis revealed that the disruption of metabolism during oocyte maturation in the CPF treatment zebrafish might interfere with F0 oocytes development and quality and ultimately influence offspring survival. For the larvae, the parental CPF exposure distinctly inhibited heart rate at 72 and 120 hpf and increased the mortality of F1 but not F2 larvae. The changes of biochemical indicators confirmed a disturbance in the oxidative balance, induced inflammatory reaction and apoptosis in F1 larvae. Furthermore, the changing profiles of mRNA revealed by RNA-seq confirmed an increased susceptibility in F1 larvae and figured out potential disruptions of ROS metabolism, immune system, apoptosis, and metabolism pathways. Taken together, these results show that chronic CPF treatment can induce reproductive toxicity, and parental transfer of CPF occurs in fish, resulting in transgenerational alters in F1 generation survival and transcription that raising concerns on the ecological risk of CPF in the natural environment.
研究领域:
环境科学
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毒理学
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水生生物学
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分子生物学
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生殖生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2023
·Vol. 24
·期 16
·12934
·
IF 5.6
Dongfang Zhang,Weikai Ding,Wei Liu,Liuying Li,Gongming Zhu,Junguo Ma
Chlorpyrifos (CPF) and glyphosate (GLY) are the most widely used organophosphate insecticide and herbicide worldwide, respectively; co-occurrence of CPF and GLY in aquatic environments occurs where they inevitably have potential hazards to fish. However, the potential mechanisms of CPF and GLY to induce toxicity have not been fully explored. To identify the adverse impacts of CPF and GLY on fish, either alone or in combination (MIX), CPF (25 μg/L) and GLY (3.5 mg/L) were set up according to an environmentally relevant concentration to expose to common carp for 21 days. After exposure, CPF and GLY decreased the activities of acetylcholinesterase and Na+/K+-ATPase, altered monoamine oxidase levels, decreased antioxidant enzyme activities (superoxide dismutase, catalase, glutathione S-transferase and glutamic reductase), and induced the accumulation of malondialdehyde in the carp brain. The parameters in the MIX groups had a greater impact compared to that in the CPF or GLY group, suggesting that both single and combined exposure could affect neurological signaling systems and cause oxidative stress and lipid peroxidation damage in carp brains, and that MIX exposure increases the impact of each pollutant. RNA-seq results showed that single or combined exposure to CPF and GLY induced global transcriptomic changes in fish brains, and the number of differentially expressed genes in MIX-treated carp brains were globally increased compared to either the CPF or GLY groups, suggesting that the effects of co-exposure were greater than single exposure. Further analysis results revealed that the global transcriptomic changes participated in oxidative stress, immune dysfunction, and apoptosis of fish brains, and identified that the P13k-Akt signaling pathway participates in both single and combined exposure of CPF- and GLY-induced toxicity. Taken together, our results demonstrated that the interaction of CPF and GLY might be synergic and provided novel insights into the molecular mechanisms of fish brains coping with CPF and GLY.Keywords:Cyprinus carpio;chlorpyrifos;glyphosate;combined exposure;neurotoxicity
研究领域:
环境毒理学
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分子生物学
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神经科学
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水生毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）