PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
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2024
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IF 4.2
Xinyu Wu,Jiawei Chen,Kaixin Ping,Yan Xia,Mengxin Li,Yannan Xiang,Huimao Feng,Jingquan Dong
Long-term residue of difenoconazole (DFZ) in the environment caused multiple organ damage to aquatic organisms. Due to the potential hepatoprotective and neuroprotective properties of silybin (SIL), we hypothesized that SIL could alleviate growth inhibition, liver, and brain damage in carp induced by DFZ exposure. The in vivo experiments were divided into the Control group, the SIL group, the DFZ group and the DFZ + SIL group. The exposure concentration of DFZ was 0.39 mg/L, and the therapeutic dose of SIL was 400 mg/kg. The whole experiment lasted for 30 days. SIL was also found to reduce hepatic injury and lipid metabolism based on H&E staining, oil red O staining, and measurement of serum and liver tissue levels of ALT, AST, LDH, TG, and TC. Similarly, SIL reduced brain damage after DFZ exposure, according to H&E staining and detection transcription level of the ZO-1, ZO-2, occludin, and Claudin7 in carp brain. In terms of mechanism, the results showed that SIL inhibited the excessive production of ROS in liver and brain tissues, increased the activity of antioxidant enzymes (T-AOC, SOD, CAT) and resist oxidative stress. Also, SIL promoted the production of anti-inflammatory factors (TGF-β1 and IL-10) and inhibited the expression of pro-inflammatory factors (TNF-α and IL-6) to reduce the inflammatory response in liver and brain tissues caused by DFZ. ln terms of ferroptosis, by lowering iron levels, upregulating ferroptosis-related genes (GPX4, SIC7A11, GCLC), and downregulating the expression of NCOA4, STEAP3, COX2, and P53, SIL was able to inhibit ferroptosis of liver and brain tissues of carp. In addition, SIL restored the reduced mitochondrial membrane potential (MMP) level and inhibited apoptosis as measured by MMP level detection, TUNEL staining, and apoptosis gene transcript levels. In this study, we analyzed the interactions between genes and proteins associated with oxidative stress, inflammation, ferroptosis and apoptosis using the String database and ranked the nodes in the network using the Cytoscape plugin Cytohubba, and found that P53, Caspase3, TNF-α, IL-6 and Bcl-2 were the key hub genes. Our study not only revealed the multiple pharmacological activities of SIL, but also provided a reference for the prevention and reduction pesticide hazards to aquatic organisms.
研究领域:
毒理学
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药理学
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环境科学
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神经科学
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肝病学
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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2024
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IF 3.9
Ying Sun,Xiaohui Jin,Zuwang Yang,Zunhan Hu,Qiulu Li,Jingquan Dong,Mian Fu
Difenoconazole (DFZ) is a widely used triazole fungicide in agricultural production. However, the presence of DFZ residue in the environment poses a significant risk to non-target organisms. Ferulic acid (FA) is a phenolic compound known for its antioxidant and anti-inflammatory properties. This study aims to investigate the hepatic damage caused by DFZ in carp and explore the mechanism through which FA alleviates this damage. The findings revealed that FA enhanced the antioxidant capability of the carp's liver and reduced the accumulation of reactive oxygen species (ROS) in the liver tissue. Moreover, FA regulated the transcriptional levels of inflammation-related factors, effectively preventing the inflammatory response triggered by the NF-κB signaling pathway. Additionally, TUNEL results demonstrated that DFZ initiated apoptosis, while dietary supplementation with FA decreased the protein expression levels of Bax and Cytochrome C (Cyt c) and the transcriptional levels of bax , caspase3 , caspase9 , p53 genes. Furthermore, FA increased the protein expression and transcriptional levels of Bcl-2. In conclusion, FA protects against liver injury induced by DFZ exposure in carp by modulating oxidative damage, inflammation, and apoptosis.
研究领域:
环境毒理学
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水生生物学
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药理学
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PubMed
高影响因子
FISH PHYSIOLOGY AND BIOCHEMISTRY
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2026
·Vol. 52
·期 2
·40
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IF 3
Zhang Shasha,Li Xinran,Gao Yaxin,Dong Qian,Jin Xiaomin,Shi Pan,Dong Jingquan
Difenoconazole (DFZ) is a persistent triazole fungicide that leads to aquatic toxicity and ecosystem damage due to its environmental persistence and high toxicity. Curcumin (CUR), a natural polyphenol derived from turmeric, exhibits strong anti-inflammatory, antioxidant, and antitumor properties. This study assesses CUR’s protective role against DFZ-induced kidney injury in carp and investigates its mechanisms. Carp were exposed to DFZ for 30 days, with dietary supplementation of 400 mg/kg CUR. H&E staining revealed that CUR significantly reduced DFZ-induced histopathological damage in the kidneys. Dihydroethidium staining and biochemical assays demonstrated that CUR effectively lowered Reactive Oxygen Species levels and lipid peroxidation. Through biochemical kits, qPCR, and Western blotting, it was found that CUR decreased T-AOC and iron content, while activating the Nrf2/HO-1 pathway, thereby alleviating ferroptosis. CUR also upregulated the expression of xCT and GPX4, increased GSH levels, and further suppressed ferroptosis. In terms of inflammation, CUR improved the response by reducing pro-inflammatory cytokines (iNOS, IL-1β, IL-6, TNF-α) and increasing anti-inflammatory factors (IL-10, TGF-β1). With regard to apoptosis, CUR inhibited pro-apoptotic proteins (Bax, Cleaved-caspase3, Cleaved-caspase9, Cytochrome c) and restored the anti-apoptotic protein Bcl-2. In conclusion, CUR alleviates DFZ-induced kidney injury in carp by inhibiting ferroptosis through the Nrf2/GPX4 axis, while reducing oxidative stress, inflammation, and apoptosis. This study highlights CUR as a promising natural agent for mitigating environmental toxicity caused by triazole fungicides. Graphical
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SCIENCE OF THE TOTAL ENVIRONMENT
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2022
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IF 10.753
Jinhua Jiang,Changpeng Zhang,Luyan Wang,Xiangyun Wang,Hongmei He,Shenggan Wu,Xueping Zhao
Limited literature had focused on the combined effect of triazole fungicides on aquatic organisms at environmental concentrations. In this research, difenoconazole (DIF) and tebuconazole (TEB) mixture exhibited additive effect on the acute toxicity to zebrafish embryos. The transcriptomics and metabolomics demonstrated DIF and TEB mixtures at aquatic life benchmark and environmental concentration simultaneously influenced the lipid metabolism, arachidonic acid metabolism, steroid hormone biosynthesis and tryptophan metabolism, but showed diverse response patterns mediating the combined effects on zebrafish embryos after 120 h exposure. The DIF and TEB mixture at aquatic life benchmark caused combined effect on yolk sac resorption and metabolites, was less than the additive effect of individual DIF and TEB. It was found environmental concentration of DIF and TEB caused much lower levels of IFN and IL6, induced higher levels of PGE 2 , l -kynurenine and formylanthranilate in zebrafish larvae, and their binary mixture caused synergistic effect on the accumulation of metabolites in metabolic pathways, which might cause more negative effect and risk on growth in zebrafish later life stages. Results further demonstrated that adding arachidonic acid (AA) increased the transcripts of Pla 2 , Ptgs1 , Cyp19a and Cxcl8b , allayed the accumulation of PLA 2 and 17 β -E 2 , and induced more PGF2 α , IFN and IL6 levels in zebrafish larvae, indicated AA metabolism might play important regulatory roles on hormone synthesis and immune response caused by DIF and TEB mixtures. Current results indicated the risk assessment of mixtures based on single concentration may not precisely estimate the environmental risk and health effect, it is crucially important to consider the multi-concentration combinations, and more attention should be paid to the environmental concentration.
研究领域:
环境毒理学
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水生生物学
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分子生物学
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药理学
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生态毒理学
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MICROCHIMICA ACTA
·
2026
·Vol. 193
·期 8
·561
·
IF 5.4
Wang Xiaoxi,Wang Haitong,Feng Bin,Liu Yu,Zhao Xinyuan,Chen Wenwen,Wei Haiyan,Zhang Wei,Wang Mengjie,Liu Chuanxi,Shang Ming,Wang Cuijuan
We developed an on-site surface-enhanced Raman scattering (SERS) sensor for rapid detection of difenoconazole (DIF) and flusilazole (FLU) in environmental water. The substrate combines gold nanostars (AuNSs) with covalent organic frameworks (COF) and is implemented on a portable round 20-well quartz plate, enabling in situ testing. After a simple filtration process, environmental water can be directly dripped onto the SERS-active AuNSs/COF composite, thereby simultaneously achieving the adsorption of the target compound and SERS detection. There is a good linear relationship between the SERS intensity of the characteristic peak and the logarithmic concentration of the analyte, with correlation coefficients (R 2 ) from 0.923 to 0.986, meeting the monitoring needs of non-laboratory scenarios. The entire workflow completes within 9 min, offering a faster alternative to conventional methods while maintaining high sensitivity and reproducibility. Detection limits reach 0.88–1.17 ppb for DIF and FLU. Distinct SERS fingerprints enable reliable discrimination of mixed pesticides across environmental water, supporting rapid on-site monitoring and cost-effective pesticide surveillance. Graphical
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Aquaculture Reports
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2024
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IF 3.2
Shuai Zhang,Xiaomeng Ji,Xiaohui Jin,Weiping Yan,Xuhui Xu,Zibo Dong
Pollution of aquatic environment by difenoconazole (DFZ) significantly affects survival and safety of freshwater aquaculture. Due to its anti-inflammatory and antioxidant properties, plant-derived quercetin (QUE) is often used as a dietary supplement. The main purpose of this study was to explore the protective effect of QUE on heart damage caused by exposure to pesticide DFZ and the potential mechanisms of these effects. This study found that QUE could effectively reduce the myocardial enzyme spectrum index of carp after exposure to DFZ, increase the levels of total antioxidant capacity (T-AOC), glutathione (GSH), and catalase (CAT), inhibit the content of malondialdehyde (MDA), and increase the transcription levels of superoxide dismutase ( sod ), glutathione peroxidase ( gsh-px ), and cat . By reducing the expression of keap1 , QUE increased the transcription levels of nrf2 and nqo-1 , reduced the production of reactive oxygen species (ROS) in the heart after exposure to DFZ, and restored the redox homeostasis of the heart. QUE upregulated the expression of anti-inflammatory cytokines il-10 and tgf-β1 levels, downregulated the transcription levels of pro-inflammatory factor inos, il-1β , il-6 and tnf-α , and alleviated the in vivo redox imbalance caused by exposure to DFZ, leading to myocardial interstitial inflammatory cell infiltration. The results showed that QUE inhibited the apoptosis after exposure to DFZ by affecting the expression of apoptotic factors in the mitochondrial apoptotic pathway. In summary, QUE can effectively decrease myocardial injury caused by exposure to DFZ in aquatic environment.
研究领域:
水生毒理学
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药理学
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环境科学
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高影响因子
JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART B-PESTICIDES FOOD CONTAMINANTS AND AGRICULTURAL WASTES
·
2026
·
IF 2
Ning Li,Yunyu Tang,Wenwen Zhang,Yang Bai,Fengshou Sun,Jin Lin
The combined application of difenoconazole and pyraclostrobin is a common strategy to combat early blight in potatoes; however, a comprehensive understanding of their co-residue behavior and associated dietary risks remains limited. In this study, a modified QuEChERS method coupled with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated for the simultaneous determination of difenoconazole and pyraclostrobin residues in potatoes. The calibration curves showed excellent linearity over the concentration range of 0.002–0.2 mg/L. At fortification levels of 0.02, 0.2, and 2 mg/kg, the average recoveries of difenoconazole ranged from 94.8 to 100.4%, with relative standard deviations (RSDs) of 0.56–1.81%; the average recoveries of pyraclostrobin ranged from 95.2 to 99.8%, with RSDs of 0.97–1.62%. The limit of quantification (LOQ) of both compounds was 0.02 mg/kg, and the instrumental limit of detection (LOD) was 2.00 × 10 g. This sensitivity is substantially better than that of conventional HPLC-UV methods (which typically exhibit LODs around 10−9 g), and the LOQ aligns with the maximum residue limit (MRL) of 0.02 mg/kg established in China. Dietary risk assessment indicated that the risk quotients (RQs) were 0.993 and 0.956 for difenoconazole and pyraclostrobin, respectively, demonstrating that the health risks to consumers are acceptable.
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AQUACULTURE
·
2023
·
IF 4.5
Enzhuang Pan,Huimiao Feng,Zuwang Yang,Yue Xin,Xiaomeng Ji,Kaixin Ping,Yong Sun,Jingquan Dong
As a widely used fungicide at present, difenoconazole can enter the aquatic ecosystem and cause adverse effects on freshwater carp culture. The spleen, an important immune organ of carp, is vulnerable to damage by environmental toxins. Studies have shown that the inflammatory response is an important mechanism of immunotoxicity of difenoconazole. Whereas quercetin has anti-inflammatory pharmacological activity, the role and mechanism of quercetin in difenoconazole-induced inflammatory damage in the spleen of carp is unknown. In this study, we developed a model for carp with quercetin added to the diet and exposed to environmentally relevant concentrations of difenoconazole. We found that quercetin protects against inflammatory damage in the splenic tissue of carp through histopathological observations. We found that quercetin alleviated ROS enrichment and disruption of redox homeostasis (dynamic balance of GSH, T-AOC, CAT, and MDA) in the spleen tissue of carp by fluorescence assay and biochemical assay. We found that quercetin was able to inhibit the activation of the NF-κB signaling pathway (elevated p-NF-κB p65 expression level) and NLRP3 inflammasome pathway (NLRP3/ASC/caspase-1) in carp spleen tissue induced by difenoconazole by immunohistochemistry and qPCR analysis. In conclusion, this study confirms that the addition of quercetin as a supplement to the diets of freshwater cultured carp is effective against the spleen toxicity induced by difenoconazole. Mechanistically, quercetin may alleviate the difenoconazole-induced splenic inflammatory injury in carp by suppressing the excessive activation of ROS/NF-κB/NLRP3 inflammasome axis, providing new insights into the mechanism of quercetin alleviation of splenic inflammatory injury in carp.
研究领域:
水产养殖
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毒理学
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免疫学
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药理学
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环境科学
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PLANT PHYSIOLOGY AND BIOCHEMISTRY
·
2025
·
IF 5.7
Jingchong Li,Wende Zheng,Jingkun Li,Komelle Askari,Zhixiang Tian,Runqiang Liu
Continuous misuse of difenoconazole (DFZ) results in farmland contamination, posing risks to crops and human health. Salicylic acid (SA) has been shown to enhance plant resistance and reduce pesticide phytotoxicity and accumulation. However, whether SA effectively reduces DFZ phytotoxicity and accumulation and its underlying mechanisms remain poorly understood. To address this, a short-term indoor experiment and a long-term outdoor pot experiment were conducted to evaluate the potential of SA to alleviate DFZ-induced phytotoxicity and its effects on DFZ uptake, translocation, metabolism, and accumulation. The underlying mechanisms were explored through physiological, biochemical, and gene expression analyses. The results showed that DFZ induced oxidative damage and reduced photosynthesis by 15.6% in wheat. SA upregulated the expression of genes encoding antioxidant enzymes ( POD , CAT , SOD1 , and SOD2 ) in the roots and leaves of DFZ-exposed plants, leading to a 7.5%–13.4% increase in antioxidant enzyme activities and a subsequent 9.7%–14.5% decrease in reactive oxygen species levels. Additionally, SA increased the total chlorophyll content by 16.3%, which was enhanced by regulating chlorophyll synthesis and degradation-related genes, thereby improving the net photosynthetic rate by 12.2%. Furthermore, SA upregulated the expression of lignin biosynthesis-related, CYP450, and GST genes, which reduced DFZ uptake and accelerated its degradation. Consequently, the wheat grain DFZ content decreased by 36.2%, thus reducing the health risk index. This study confirms the potential of SA to reduce DFZ phytotoxicity and accumulation. Based on these findings, we recommend using SA in DFZ-contaminated areas to mitigate phytotoxicity and the associated human dietary exposure risks.
研究领域:
植物学
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环境科学
·
分子生物学
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FOOD CHEMISTRY
·
2026
·
IF 10.4
Haitong Wang,Cunxiang Bo,Bingxin Xu,Yu Liu,Mengping Zhang,Xinyuan Zhao,Liqun Song,Hua Shao,Cuijuan Wang
•AuNPs-modified COF on a portable 25-well plate for testing DIF and FLU residues. • •Integration of adsorption and SERS functions for streamlined analyses. • • Portable, on-site detection system enabling field-ready pesticide monitoring. • • Ready-to-use, pretreatment-free SERS assay delivering real-time results. We developed a ready-to-use surface-enhanced Raman scattering (SERS) sensor for rapid, pretreatment-free detection of difenoconazole (DIF) and flusilazole (FLU) in peach and lychee juices. The substrate combines Au nanoparticles (AuNPs) with covalent organic frameworks (COF) and is implemented on a portable 25-well plate, enabling in situ testing. Juices can be directly applied to the SERS-active Au/COF composite, allowing simultaneous adsorption and signal generation. The correlation between SERS intensity and logarithmic concentration yielded R-values between 0.925 and 0.986, meeting the monitoring needs of non-laboratory scenarios. The entire workflow completes within 12 min, offering a faster alternative to conventional methods while maintaining high sensitivity and reproducibility. Detection limits reach 0.96–1.22 ppb for DIF and FLU, both of which are below the regulatory maximum residue limits. Distinct SERS fingerprints enable reliable discrimination of mixed residues across juice matrices, supporting rapid on-site monitoring and cost-effective pesticide surveillance. Download: Download high-res image (233KB) Download: Download full-size image
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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Jingchong Li,Zhixiang Tian,Aohui Han,Jingkun Li,Aodi Luo,Runqiang Liu,Zhiyong Zhang
Difenoconazole (DFN) is widely utilized as a fungicide in wheat production. However, its accumulation in plant tissues has a profound impact on the physiological functions of wheat plants, thus severely threatening wheat growth and even jeopardizing human health. This study aims to comprehensively analyze the dynamic dissipation patterns of DFN, along with an investigation into the physiological, hormonal, and transcriptomic responses of wheat seedlings exposed to DFN. The results demonstrated that exposure of wheat roots to DFN (10 mg/kg in soil) led to a significant accumulation of DFN in wheat plants, with the DFN content in roots being notably higher than that in leaves. Accumulating DFN triggered an increase in reactive oxygen species content, malonaldehyde content, and antioxidant enzyme activities, while concurrently inhibiting photosynthesis . Transcriptome analysis further revealed that the number of differentially expressed genes was greater in roots compared with leaves under DFN stress. Key genes in roots and leaves that exhibited a positive response to DFN-induced stress were identified through weighted gene co-expression network analysis. Metabolic pathway analysis indicated that these key genes mainly encode proteins involved in glutathione metabolism, plant hormone signaling, amino acid metabolism , and detoxification/defense pathways. Further results indicated that abscisic acid and salicylic acid play vital roles in the detoxification of leaf and root DFN, respectively. In brief, the abovementioned findings contribute to a deeper understanding of the detrimental effects of DFN on wheat seedlings, while shedding light on the molecular mechanisms underlying the responses of wheat root and leaves to DFN exposure.
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CHEMOSPHERE
·
2023
·
IF 8.8
Yajie Chen,Xingang Liu,Yanming Zhou,Lan Zhang,Liangang Mao,Lizhen Zhu,Yongquan Zheng
The aim of this study was to assess the bioavailability of epoxiconazole (EPO) and difenoconazole (DIF) in rice plants by evaluating their uptake, translocation, and accumulation. The results showed that the concentration of DIF in the roots was approximately three times higher than EPO, and both accumulated mainly in the roots. In addition, EPO continued to be transported from stems to leaves, causing a rise in its concentration in leaves. Contrastingly, only a minimal amount of DIF was transported to the leaves. This phenomenon is mainly governed by their differing octanol-water partition coefficient . The effects of dissolved organic carbon (DOC) on the accumulation of EPO and DIF in the roots were similar to those of the freely dissolved concentration measured by OECAMs . The concentrations of EPO and DIF in the roots and OECAMs consistently decreased with increasing DOC levels. Furthermore, a significant linear relationship was observed between the EPO and DIF concentrations in root and OECAMs. We also confirmed the accuracy and usefulness of the OECAMs method in predicting the bioavailability of EPO and DIF in rice roots. Therefore, OECAMs show good potential for use as a passive sampler to evaluate the bioavailability of EPO and DIF.
研究领域:
环境科学
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植物生理学
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高影响因子
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