CHEMOSPHERE
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2022
·
IF 8.943
Fang Jiao,Yongfang Ma,Tiantian Hu,Kun Qiao,Yao Jiang,Wei Zhu,Quan Jin,Wenjun Gui
The transgenerational effect assessment linked to epigenetic analysis of environmental pollutants on eco (toxico)logical relevant species is regarded as a potential future risk-assessment tool. As an organotin acaricide widely used in China, azocyclotin can lead to endocrine disrupting effect on directly exposed environmental organisms, but whether it has transgenerational negative impact remains unknown. In order to illustrate this issue, in the present study, zebrafish, an aquatic model animal, was exposed to azocyclotin at less than μg/L level in a time span of embryonic stage to adult stage. Subsequently, the developmental and reproductive endocrine disrupting effects of azocyclotin on exposed F0 and unexposed offspring (F1 and F2) were evaluated. Result indicated that parentally exposed to 0.36 μg/L azocyclotin induced embryonic toxicity to unexposed offspring, and significantly ( p < 0.05) reduced body weight (by 8.5%–13.9%), whole body length (by 4.8%–14.3%), hepatosomatic index (by 15.6%–24.3%), gonadosomatic index (by 5.3%–17.1%), egg production (by 19.5%–25.4%), estradiol content (47.0%–65.0%) and proportion of mature germ cells (by 29.3%–41.0% and 39.2%–47.7% for late oocytes and spermatozoa, respectively) in adults of F0 and offspring. Additionally, azocyclotin decreased the contents of 5-methycytosine in gonads of unexposed offspring (by 9.9%–38.6%, p < 0.05), led to genome-wide gene up-regulated expression bias and genomic DNA hypomethylation tendency in unexposed offspring. Moreover, based on the level of differentially methylated cytosine in promoter regions/gene body regions, it was found totally 5331/11,170 (in F1) and 3808/7507 (in F2) differentially expressed genes were closely related with differentially methylated genes (r > 0.6). The present study provided a primary evidence that prolonged exposure to low dose azocyclotin induced inter- and transgenerational endocrine disrupting effects on zebrafish probably linked to transcriptomic and DNA methylomic alterations.
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Nutrients
·
2021
·Vol. 13
·期 12
·4379
·
IF 5.719
Hui Zhou,Yuanyuan Wu,Eunhye Kim,Haibo Pan,Puming He,Bo Li,Yi Charlie Chen,Youying Tu
Theaflavin-3,3′-digallate (TF3) is the most important theaflavin monomer in black tea. TF3 was proved to reduce blood glucose level in mice and rats. However, the elaborate anti-diabetic mechanism was not well elucidated. In this work, human hepatoma G2 (HepG2) cells and zebrafish (Danio rerio) were used simultaneously to reveal anti-diabetic effect of TF3. The results showed that TF3 could effectively rise glucose absorption capacity in insulin-resistant HepG2 cells and regulate glucose level in diabetic zebrafish. The hypoglycemic effect was mediated through down-regulating phosphoenolpyruvate carboxykinase and up-regulating glucokinase. More importantly, TF3 could significantly improve β cells regeneration in diabetic zebrafish at low concentrations (5 μg/mL and 10 μg/mL), which meant TF3 had a strong anti-diabetic effect. Obviously, this work provided the potential benefit of TF3 on hypoglycemic effect, regulating glucose metabolism enzymes, and protecting β cells. TF3 might be a promising agent for combating diabetes.Keywords:theaflavin-3,3′-digallate;anti-diabetic effect;HepG2 cells;diabetic zebrafish model;glucose metabolism enzymes
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
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2019
·
IF 3.061
Yinghan Liu,Zhuang Wang,Se Wang,Hao Fang,Nan Ye,Degao Wang
The importance of attention to unravel the interaction of nano-plastic particles (NPs) with natural acidic organic polymer (NAOP) in freshwater environment should not be neglected. However, toxicological data available for the interaction between NPs and NAOP remain limited. Here, we investigate the toxicological effects of three model polystyrene (PS) NPs with different functional groups (unmodified, amino- and carboxyl-modified PS NPs) on two freshwater organisms of different trophic levels ( Scenedesmus obliquus and Danio rerio ) in the absence and presence of two classes of NAOP, namely fulvic acid and humic acid. The NAOP interaction with the NPs is shown to alter oxidative stress and disturb membrane function in S. obliquus cells to a certain extent. Combined oxidative stress responses to the NPs and NAOP in D. rerio as a function of their mixture levels showed inhibition, alleviation, and reinforce. Changes in cellular oxidative stress and membrane function depended on the concentration and types of both NPs and NAOP. Furthermore, the characterization parameters of the NPs were important for the explanation of the ecotoxicological mechanism of the NPs in the presence of NAOP. Our findings emphasized the critical role of NAOP in the fate and toxicity of plastic particles in freshwater environment.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2019
·
IF 4.527
Guihua Wang,Jian Shao,Manni Wu,Yanxiao Meng,Yasmeen Gul,Hui Yang,Dongmei Xiong
Triazophos (TAP) has become a part of widespread pollutant of the aquatic environment due to its residue. Current study was designed to investigate the toxic effect of TAP at different doses (0.06, 0.3 and 1.5 mg/L) to the model organism of zebrafish ( Danio rerio ) by using multi-endpoint analysis in a 96 h acute exposure test. The direct observation that histological and ultrastructural alteration of zebrafish brain and liver were carried out via paraffin section in hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM), respectively. In addition, a series of methods were applied for exploring the physiological parameters related to cellular apoptosis. Results indicated that vacuolar structure after 96 h treatment with TAP were appeared in the molecular and granular layers of cerebellum. A large number of nuclear retraction, tissues vacuolation and cytoplasmic loss were observed in liver at histological level. From the fine structural level, the mitochondrial vacuolation and membrane damage of brain cells were found and the cristae of mitochondria disintegrated partly in hepatocytes. Onset of such histological structure alterations were one of the most intuitive reflection to TAP exposure, which needs to analyze biochemical alterations for further study. The mitochondrial membrane potential (MMP) showed a downward trend in the brain and liver of zebrafish. Simultaneously, the activity of caspase-3 and caspase-9 increased after 96 h exposure with a concentration-dependent manner, which could be served as a suitable indicator of cellular apoptosis. Furthermore, apoptosis-related genes ( Apaf-1, p53, Bax, Bcl-2, caspase-3 and caspase-9 ) transcription showed different alterations in response to the TAP treatment. These results indicated that TAP exposure led to apoptosis in zebrafish brain and liver and it was speculated that the apoptosis may occur through mitochondrial pathway. The present study demonstrated that the exposure of zebrafish to the insecticide TAP led to observe its effects at both histological structure and apoptosis level in liver and brain.
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AQUATIC TOXICOLOGY
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2016
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IF 3.557
Jieyi Li,Jinfeng Liu,Yuhuan Zhang,Xuedong Wang,Weijun Li,Hongqin Zhang,Huili Wang
The toxicity of β-diketone antibiotics (DKAs) to larval and adult zebrafish ( Danio rerio ) was investigated by miRNA sequencing and bioinformatics analyses. In control and DKA-exposed groups, 215 differentially expressed miRNAs were screened, and 4076 differential target genes were predicted. Among 51 co-differentially expressed genes, 45 were annotated in KOG functional classification, and 34 in KEGG pathway analysis. The homology analysis of 20 miRNAs with human hsa-miRNAs demonstrated 17 high homologous sequences. The expression levels of 12 miRNAs by qRT-PCR were consistent with those by sRNA-seq. A regulatory network for 4 positive miRNA genes (dre-miR-10, ⿿96, ⿿92 and ⿿184) was plotted, and the high-degree of connectivity between miRNA-gene pairs suggests that these miRNAs play critical roles during zebrafish development. The consistent expression of dre-miR-184 and dre-miR-96 was proved in 120-hpf zebrafish brain, gill, otoliths and lateral line neuromast by qRT-PCR, miRNA-seq, W-ISH and ISH. DKA-exposure led to vacuolation of interstitial cells, reduced number of neurons, glial cell proliferation and formation of glial scar, and the obvious abnormality of cell structure might result from abnormal expression of differentially expressed miRNAs. In general, chronic DKA-exposure resulted in comprehensively toxic effects on larval and adult zebrafish tissues, especially for nervous system.
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JOURNAL OF HAZARDOUS MATERIALS
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2025
·
IF 11.3
Chenyang Rao,Yanxia Zuo,Dongfang Xiang,Bo Xian,Fuhao Chu,Fang Fang,Xiaowei Xiang,Wei Tang,Shaopan Bao,Tao Fang
In recent years, N -(1,3-dimethylbutyl)- N′ -phenyl- p -phenylenediamine (6PPD) has attracted significant attention in environmental science, yet its behavior in biological systems remains poorly understood. This study involved a 28-day zebrafish exposure experiment at three concentrations (2, 20, and 200 μg/L), to investigate its physiologically based toxicokinetic (PBTK) properties, the formation of biotransformation products, and the metabolic characteristics of liver tissue. The results indicated that the liver and intestines are key organs for 6PPD accumulation, with tissue-specific distribution patterns. The biotransformation of 6PPD in the liver involves various phase I and phase II metabolic reactions, including hydroxylation, N -dealkylation, and sulfation processes. Furthermore, Metabolomics analysis revealed substantial changes in both the diversity and abundance of liver metabolites with increasing 6PPD concentrations, particularly in key biological processes such as lipid metabolism, amino acid metabolism, and redox balance. Notably, significant disruptions in sphingolipid and glycerophospholipid pathways suggest 6PPD may impair membrane fluidity and stability, potentially leading to membrane damage and dysfunction. Overall, this study provides crucial insights into the biological behavior of 6PPD in zebrafish, contributing essential knowledge for its ecotoxicological evaluation.
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ENVIRONMENTAL POLLUTION
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2025
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IF 7.3
Qiuhui Qian,Ji Wu,Cuizhen Wang,Zheng Yang,Ying Cheng,Yuansi Zheng,Xuedong Wang,Huili Wang
As a synthetic rubber antioxidant, the environmental monitoring concentrations of N-(1,3-Dimethylbutyl)-N′-phenyl-p-phenylenediamine (6-PPD) have exceeded the risk threshold, attracting widespread attention. Although investigations into the harmful effects on zebrafish have commenced, a comprehensive exploration of its toxicological impacts and underlying molecular mechanisms remains to be conducted. By using zebrafish as a model, this study systematically evaluated 6-PPD-induced lipid metabolism disorders and inflammation response following environmental exposure. Bioinformatics analysis revealed that 6-PPD target genes enriched in the hepatitis B pathway, indicating potential hepatic toxicity via inflammatory pathways. Therefore, we hypothesize that 6-PPD could trigger hepatotoxicity through the crosstalk between lipid metabolism and inflammation. Further experiments substantiated this hypothesis by showing lipid accumulation in the liver following 6-PPD exposure, along with elevated triglyceride (TG) and total cholesterol (TC) levels, and imbalanced expression of lipid metabolism-related marker genes. Additionally, 6-PPD exposure induced the accumulation of reactive oxygen species (ROS) and inhibited the differentiation and maturation of immune cells, resulting in immune evasion. Most of these abnormalities were exacerbated in a dose-dependent manner with increasing concentrations of 6-PPD. The addition of the PPARγ pathway agonist puerarin (PUE) or NF-κB pathway inhibitor quinazoline (QNZ) to 6-PPD exposure group mitigated these toxic effects, validating our conjecture that lipid metabolism disorder and inflammatory responses may result from the regulation of the PPARγ/NF-κB pathway.
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AQUATIC TOXICOLOGY
·
2024
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IF 4.1
Huan-Yu Tao,Jianghong Shi,Jiawei Zhang,Hui Ge,Mengtao Zhang,Xiao-Yan Li
Diisobutyl phthalate (DiBP), is widely chemical replacement for Dibutyl phthalate (DBP). Although DBP and DiBP have been detected in surface water worldwide, few studies to date have systematically assessed the risks of DBP and its alternatives to aquatic organisms. The present study compared DBP and DiBP for their individual and joint toxicity as well as thyroid hormone levels in zebrafish embryo. Transcripts of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were investigated in developing zebrafish larvae by application of real time polymerase chain reaction. The median half-lethal concentrations of DBP and DiBP to zebrafish at 96 h were 0.545 mg L −1 and 1.149 mg L −1 , respectively. The joint toxic effect of DBP–DiBP (0.25–0.53 mg L −1 ) with the same ratio showed a synergistic effect. Thyroid hormones levels increased with exposure to 10 μg L −1 of DBP or 50 μg L −1 of DiBP, and exposure to both compounds significantly increased thyroid gland-specific transcription of thyroglobulin gene ( tg ), hyronine deiodinase ( dio2 ), and transthyretin ( ttr ), indicating an adverse effect associated with the HPT axis. Molecular docking results indicated that DBP (−7.10 kcal/M and −7.53 kcal/M) and DiBP (−6.63 kcal/M and −7.42 kcal/M) had the same docking energy with thyroid hormone receptors. Our data facilities an understand of potential harmful effects of DBP and its alternative (DiBP).
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Water Reuse
·
2023
·Vol. 13
·期 1
·82-96
·
IF 4.5
Yuan Zixi,Li Ruixuan,Li Shuangshuang,Qiu Denggao,Li Guanyi,Wang Chun,Ni Jiajia,Sun Yingxue,Hu Hongying
Zinc is one of the heavy metals present in textile wastewater with high concentrations. However, the chronic toxic effects of zinc on aquatic vertebrates are still ambiguous. Zinc accumulation in zebrafish after chronic zinc exposure and toxic effects on the intestines, muscles, and gills were investigated in this study. The results showed that a significant accumulation of zinc in the intestine, muscle, and gill was observed after 25 d of zinc exposure. The toxic effects of zinc were mainly in the form of zinc-induced oxidative stress in zebrafish, potential neurotoxicity, and changes in intestinal microbes. Significant changes in the levels of superoxide dismutase, catalase, metallothionein, glutathione, and malondialdehyde indicated that zinc damaged the antioxidant system of adult zebrafish. Zinc exposure resulted in a significant decrease in acetylcholinesterase activity and abnormal neural signaling. Furthermore, zinc exposure resulted in increased intestinal microbial richness and decreased the Simpson index in adult zebrafish. At the phylum and genus levels, the predominant microbes in the intestine are altered by zinc. In summary, this study provides an analysis of the toxic effects of chronic zinc exposure on adult zebrafish and the potential mechanisms, which are important for assessing the dual effects of zinc on aquatic organisms. Zinc accumulation in adult zebrafish organs is significantly associated with oxidative stress. Differences in oxidative stress of different organs to chronic zinc exposure were found. Zinc adversely affects the nervous system of adult zebrafish. The effect of zinc on the intestinal microbiome of adult zebrafish is twofold.
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Frontiers in Cell and Developmental Biology
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2021
·
IF 6.684
Salehpour Aria,Rezaei Mohammad,Khoradmehr Arezoo,Tahamtani Yaser,Tamadon Amin
Despite extensive studies on type 2 diabetes mellitus (T2DM), there is no definitive cure, drug, or prevention. Therefore, for developing new therapeutics, proper study models of T2DM is necessary to conduct further preclinical researches. Diabetes has been induced in animals using chemical, genetic, hormonal, antibody, viral, and surgical methods or a combination of them. Beside different approaches of diabetes induction, different animal species have been suggested. Although more than 85% of articles have proposed rat (genus Rattus) as the proper model for diabetes induction, zebrafish (Danio rerio) models of diabetes are being used more frequently in diabetes related studies. In this systematic review, we compare different aspects of available methods of inducing hyperglycemia referred as T2DM in zebrafish by utilizing a scoring system. Evaluating 26 approved models of T2DM in zebrafish, this scoring system may help researchers to compare different T2DM zebrafish models and select the best one regarding their own research theme. Eventually, glyoxalase1 (glo1−/−) knockout model of hyperglycemia achieved the highest score. In addition to assessment of hyperglycemic induction methods in zebrafish, eight most commonly proposed diabetic induction approval methods are suggested to help researchers confirm their subsequent proposed models.
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TOXICOLOGY
·
2021
·
IF 4.221
Xiao Y. Li,Ying J. Qin,Yue Wang,Tao Huang,Yuan H. Zhao,Xiao H. Wang,Christopher J. Martyniuk,Bing Yan
Strobilurin fungicides are used globally and have been detected in microgram per liter concentrations in aquatic environments. Here, we determined the potential toxicity of four commonly used strobilurins (azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin) on mitochondrial function and locomotor activity of larval zebrafish at an environmentally relevant level. As the mode of action of strobilurins in fungi is binding to cytochrome bc1 in mitochondrial complex III, we evaluated exposure effects on mitochondrial oxidative phosphorylation of zebrafish, by measuring oxygen consumption rates, mitochondria-related enzyme activities , and transcripts levels for genes associated with the electron transfer chain and citric acid cycle. We found that 50 nM pyraclostrobin and trifloxystrobin lowered basal respiration, oligomycin-induced ATP respiration, and maximal respiration of embryos. Dysfunction in mitochondrial bioenergetics was associated with changes in mitochondrial complex III activity and transcripts of oxidative respiration and stress-related genes. Lower activity of complex III, and reduced cytb mRNA levels were hypothesized to contribute to reduced electron supply to complex IV and V. Both coxI and atp6 were up-regulated, suggesting a compensatory response to impaired oxidative respiration. Cluster analysis indicated that strobilurin-induced oxidative stress and cytb transcript were related to impaired oxidative phosphorylation. We also assessed larval behavior responses, as reduced ATP can affect activity. We observed that pyraclostrobin and trifloxystrobin induced hypoactive responses in zebrafish. At 50 nM, azoxystrobin and kresoxim-methyl exerted no effects on mitochondrial function nor locomotion of zebrafish. Studies such as this are important for determining sublethal toxicity to these fungicides, as widespread detection of strobilurins in aquatic environments suggests there is a potential for adverse effects in aquatic organisms .
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ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2018
·Vol. 25
·期 10
·9636-9646
·
IF 2.8
Li Chenguang,Qu Ruijuan,Chen Jing,Zhang Shuo,Allam Ahmed A.,Ajarem Jamaan,Wang Zunyao
Triclosan (TCS) is an antibacterial and antifungal agent widely used in personal care products, and it has been frequently detected in the aquatic environment. In the present study, the acute toxicity of TCS to Daphnia magna , Photobacterium phosphoreum , Danio rerio , and Limnodrilus hoffmeisteri was assessed under different pH conditions. Generally, TCS was more toxic to the four aquatic organisms in acidic medium. The LC 50 values for D. magna and D. rerio were smaller among the selected species, suggesting that D. magna and D. rerio were more sensitive to TCS. In addition, the oxidative stress-inducing potential of TCS was evaluated in Carassius auratus at three pH values. Changes of superoxide dismutase (SOD) and catalase (CAT) activity, glutathione (GSH) level, and malondialdehyde (MDA) content were commonly observed in all TCS exposure groups, indicating the occurrence of oxidative stress in the liver of C. auratus . The integrated biomarker response (IBR) index revealed that a high concentration of TCS induced great oxidative stress in goldfish under acidic condition. This work supplements the presently available data on the toxicity data of TCS, which would provide some useful information for the environmental risk assessment of this compound.
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危险品化学品经营许可证（带存储）