AQUATIC TOXICOLOGY
·
2023
·
IF 4.5
Qiang Luo,Liping Ai,Shuqiong Tang,Hua Zhang,Jinze Ma,Xiaoping Xiao,Keyuan Zhong,Guiyou Tian,Bo Cheng,Cong Xiong,Xiaobei Chen,Huiqiang Lu
Ethyl 3-(N-butylacetamido) propanoate (EBAAP) is one of the most widely used mosquito repellents worldwide, and is also commonly used to produce cosmetics. Residues have recently been detected in surface and groundwater in many countries, and their potential to harm the environment is unknown. Therefore, more studies are needed to fully assess the toxicity of EBAAP. This is the first investigation into the developmental toxicity and cardiotoxicity of EBAAP on zebrafish embryos. EBAAP was toxic to zebrafish, with a lethal concentration 50 (LC50) of 140 mg/L at 72 hours post fertilization (hpf). EBAAP exposure also reduced body length, slowed the yolk absorption rate, induced spinal curvature and pericardial edema, decreased heart rate, promoted linear lengthening of the heart, and diminished cardiac pumping ability. The expression of heart developmental-related genes ( nkx2.5, myh6, tbx5a, vmhc, gata4, tbx2b ) was dysregulated, intracellular oxidative stress increased significantly, the activities of catalase (CAT) and superoxide dismutase (SOD) decreased, and malondialdehyde (MDA) content increased significantly. The expression of apoptosis-related genes ( bax/bcl2, p53, caspase9, caspase3 ) was significantly upregulated. In conclusion, EBAAP induced abnormal morphology and heart defects during the early stages of zebrafish embryo development by potentially inducing the generation and accumulation of reactive oxygen species (ROS) in vivo and activating the oxidative stress response. These events dysregulate the expression of several genes and activate endogenous apoptosis pathways, eventually leading to developmental disorders and heart defects.
研究领域:
毒理学
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环境科学
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发育生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2025
·
IF 2.8
Nian Liu,Shuchao Zhang,Yiliang Liu,Xing Lu,Xiaozhen He
Carbimazole, a first-line antithyroid agent, alleviates hyperthyroidism by inhibiting thyroid hormone synthesis. However, its clinical use is complicated by adverse effects such as cardiotoxicity and hepatotoxicity, underscoring the need to elucidate its mechanisms in model organisms. In this study, zebrafish embryos at 6-h postfertilization (hpf) were continuously exposed to increasing carbimazole concentrations, with systematic assessment of developmental and physiological parameters. Results demonstrated that concentrations above 3.5 μg/mL caused significant mortality and delayed hatching. Dose-dependent developmental abnormalities included shortened body length, reduced swim bladder area, and pericardial edema. Further analyses indicated carbimazole-induced cardiotoxicity characterized by impaired cardiac development, decreased heart rate, and dysregulation of apoptosis-related genes. A diminished fluorescence area suggested compromised cardiac tissue integrity. Concurrently, hepatotoxicity manifested as yolk sac enlargement and altered expression of liver-specific genes, indicating disrupted hepatic function. RNA sequencing (RNA-seq) analyses indicated that at 120 hpf, the 5-μg/mL carbimazole-treated group exhibited 158 upregulated genes and 562 downregulated genes compared with the wild-type (WT) group. GO and KEGG enrichment analyses revealed disruptions in several signaling pathways associated with liver metabolism and cardiac development, including metabolism, FoxO signaling, and the p53 signaling pathway. These findings demonstrate that carbimazole induces early embryonic developmental abnormalities, cardiotoxicity, and hepatotoxicity in zebrafish. This research provides new insights into carbimazole toxicity and valuable perspectives for optimizing its clinical dosing regimen.
研究领域:
药理学
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毒理学
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发育生物学
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分子生物学
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基因组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2018
·
IF 4.946
Hossein Mohammadzadeh-Aghdash,Yousef Sohrabi,Ali Mohammadi,Dariush Shanehbandi,Parvin Dehghan,Jafar Ezzati Nazhad Dolatabadi
Cytotoxicity and genotoxicity of sodium acetate (SA), sodium diacetate (SDA), and potassium sorbate (PS) was tested on Human Umbilical Vein Endothelial Cells (HUVEC). Cytotoxicity was investigated by MTT assay and flow cytometry analysis, while genotoxicity was evaluated using DNA fragmentation and DAPI staining assays. The growth of treated HUVECs with various concentrations of SA , SDA and PS decreased in a dose-and time-dependent manner. The IC50 of 487.71, 485.82 and 659.96 µM after 24 h and IC50 of 232.05, 190.19 and 123.95 µM after 48 h of treatment were attained for SA, SDA and PS, respectively. Flow cytometry analysis showed that early and late apoptosis percentage in treated cells was not considerable. Also neither considerable DNA fragmentation nor DNA smear was observed using DAPI staining and DNA ladder assays. Overall, it can be concluded that the aforementioned food additives can be used as safe additives at low concentration in food industry.
研究领域:
毒理学
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食品科学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Ruyi Feng,Yanlu Li,Junxia Ma,Yanchao Xing,Yingshan Jiang,Zhongmei He,Ying Zong,Rui Du
Ethnopharmacological relevance Spermatogenic Pill (SP) is a commonly used clinical preparation in the Third Clinical Hospital of Changchun University of Traditional Chinese Medicine. Has accumulated a good reputation for more than a decade. However, because SP is a hospital clinical agent, it has received little extensive attention from researchers, which has led to a systematic lack of basic research on it. Therefore, it is impossible to determine whether there are safety hazards that may limit its widespread clinical application, and an in-depth toxicological evaluation of SP is essential and urgent. Aim of the study The aim of this study was to assess the safety of SP by conducting acute and subacute toxicity examinations. Materials and methods Identify active compounds contained in SP by LC-MS, and determination of inorganic elements in SP using ICP-MS. The in vivo acute toxicity of SP was assessed over a duration of 14 days following administration at doses of 7.5, 15, or 30 g/kg. To evaluate subacute toxicity, mice were administered daily doses of SP (7.5, 15, or 30 g/kg) for a period of 28 days. After the treatment period, the animals were euthanized, and standard blood tests, liver and kidney function tests, as well as tests related to glycolipid metabolism, were performed. The principal organs of the mice were collected to calculate organ coefficients and undergo hematoxylin-eosin (HE) staining. Results LC-MS analysis showed that the active components of SP include Quercetin, Kaempferol, Beta-sitosterol, Stigmasterol, Diosbulbin B, Schizandrin, Naringenin, 2,3-hydroxycinnamic acid, L-proline, Histidine and Pluviatolide. The total amount of detected inorganic elements accounted for 3.0919% of SP. During the SP acute toxicity experiment, the groups that received the drug exhibited no signs of adverse reactions or poisoning symptoms. In subacute toxicity experiments, drug-treated mice showed overall favorable status, but the effects of continuous administration of the 30 g/kg group on body weight and food intake were reduced. An increase in the white marrow of spleen tissue after long-term administration of the drug treatment was also observed, suggesting that the drug can increase the maturation process and the number of mature lymphocytes in the spleen, and improve the lymphocyte immunity and humoral immunity function of the organism. Suggests that possibly this should be taken into account in clinical application. The routine blood examinations, as well as the assessments of liver and kidney functions, and the tests for glucose and lipid metabolism, did not reveal any notable toxic effects. Conclusion SP contains more flavonoids, and terpenoid active ingredients, and is non-toxic in the body. This discovery not only strengthens the safety foundation of its clinical application, provides a solid scientific basis for the establishment of reasonable clinical dosage and the implementation of effective clinical toxicity monitoring, but also further lays a solid theoretical cornerstone for the subsequent clinical drug trials.
研究领域:
药理学
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毒理学
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中医药学
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2020
·
IF 4.679
Zengqiang Li,Yige Yu,Yang Li,Feifei Ma,Yinghui Fang,Chaobo Ni,Keyang Wu,Peipei Pan,Ren-Shan Ge
Di-n-butyl phthalate (DBP) is widely used in consumer products as a plasticizer . Here, we report a natural product taxifolin that can attenuate developmental and reproductive toxicity of DBP. Pregnant rats were daily gavaged with 500 mg/kg DBP alone or together with taxifolin (10 and 20 mg/kg) from gestational day (GD) 12–21. At GD21, sera and testes of male fetus were collected. DBP significantly lowered serum testosterone level at 500 mg/kg and taxifolin can completely reverse its action. DBP caused abnormal aggregation of fetal Leydig cells and taxifolin can reverse it. DBP down-regulated the expression of the genes of cholesterol side-chain cleavage enzyme ( Cyp11a1 ), 17β-hydroxysteroid dehydrogenase 3 ( Hsd17b3 ), and insulin-like 3 ( Insl3 ) and taxifolin can reverse its action. DBP increased malondialdehyde levels and decreased superoxide dismutase and glutathione peroxidase expression and taxifolin can reverse it. DBP increased incidence of multinucleated gonocytes and taxifolin can prevent it. Moreover, DBP lowered sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) and phosphorylated AMP-activated protein kinase (pAMPK) signalling and taxifolin antagonized DBP. In conclusion, in utero exposure to DBP caused developmental/reproductive toxicity of male offspring via increasing reactive oxygen species and taxifolin is an effective food component that completely reverses DBP-mediated action.
研究领域:
毒理学
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生殖健康
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环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY
·
2019
·Vol. 38
·期 10
·2169-2177
·
IF 3.421
An He,Xinyong Liu,Liang Qu,Yongfei Gao,Jianfeng Feng,Lin Zhu
We exposed zebrafish ( Danio rerio ) to different concentrations of lead and cadmium, and monitored them for survival at 24, 48, 72, and 96 h. Metal toxicity was predicted and compared using the dose–response and general threshold survival models in terms of required data sets, fit performance, and applicability. Environ Toxicol Chem 2019;38:2169–2177. © 2019 SETAC.
研究领域:
环境毒理学
·
生态学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2017
·
IF 6.065
Xiao H. Wang,Ling Y. Fan,Shuo Wang,Yue Wang,Li C. Yan,Shan S. Zheng,Christopher J. Martyniuk,Yuan H. Zhao
Chemicals show diverse modes of action (MOAs) in aquatic organisms depending upon acute and chronic toxicity evaluations. Here, toxicity data for Vibrio fischeri involving 52 compounds for acute and chronic toxicity were used to determine the congruence of acute and chronic toxicity for assessing MOAs. Using toxic ratios, most of the compounds categorized into MOAs that included baseline, less inert or reactive compounds with acute toxicity were also categorized as baseline, less inert or reactive compounds with chronic toxicity. However, significantly different toxic effects were observed with acute and chronic toxicity for the reactive and specific-acting compounds. The acute-chronic toxic ratios were smaller and less variable for the baseline and less inert compounds, but were greater and more variable for the reactive and specific-acting compounds. Baseline and less inert compounds share same MOAs, but reactive and specific-acting compounds have different MOAs between acute and chronic toxicity. Bioconcentration processes cannot reach an equilibrium for highly hydrophilic and ionized compounds with short-term exposure, resulting in lower toxicity compared to long-term exposure. Pronounced differences for the antibiotics were not only due to the difference in bioconcentration, but also due to a predicted difference in MOAs during acute and chronic exposures.
研究领域:
环境毒理学
·
生态学
✓ 已验证
DOI
PubMed
高影响因子
LIMNOLOGY
·
2018
·Vol. 20
·期 2
·173-179
·
IF 1.13
Du Jingjing,Qv Mingxiang,Li Ke,Yin Xiaoyun,Meng Fanxiao,Yang Jingchao,Ma Chuang
The impacts of three commonly used benzophenone-type UV filters including benzophenone (BP), 2-hydroxy-4-methoxy-benzophenone (BP3), and 2-hydroxy-4-methoxy-benzophenone-5-sulfonicacid (BP4) were assayed in vitro using a cladoceran Daphnia carinata . The 24-h LC50 on D. carinata calculated for BP, BP3, and BP4 was 8.37, 2.18, and 82.27 mg l −1 , respectively. BP3 and BP4 significantly impacted on the time of D. carinata first molting at a concentration of 0.1 µg l −1 . BP4 had an inhibitory effect on D. carinata molting and BP3 had an inhibitory effect on D. carinata pregnancy at a concentration of 1 µg l −1 . Furthermore, BP4 significantly inhibited the number of D. carinata first brood per female at a concentration of 10 µg l −1 . All of the endpoints from acute and chronic toxicity demonstrated that the hydroxy group in BP3 and BP4 significantly enhanced the toxic effect compared to BP. Therefore, the toxicity of BP-type UV filters is related to their molecular structure.
研究领域:
环境科学
·
毒理学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Nanomedicine
·
2013
·
IF 3.463
Sai-Ping Jiang,Sai-Nan He,Yun-Long Li,Da-Lin Feng,Xiao-Yang Lu,Yong-Zhong Du,He-Yong Yu,Fu-Qiang Hu,Hong Yuan
Purpose Safe and effective lipid nanoemulsion (LNE) formulations for the antitumor delivery of doxorubicin is designed.Methods LNEs composed of medium-chain triglyceride, soybean oil, lecithin, and doxorubicin are prepared by a solvent-diffusion method in an aqueous system. The effects of lipid material composition and polyethylene glycol (PEG)ylation on the size, drug encapsulation efficiency, and stability of LNEs are investigated. Based on in-vitro cytotoxicity and cellular uptake tests of A549 (human lung carcinoma) cells, in-vivo biodistribution, antitumor activity, and cardiac toxicity are further examined using nude mouse bearing A549 tumor.Results The LNE size decreases from 126.4 ± 8.7 nm to 44.5 ± 9.3 nm with increased weight ratio of medium-chain triglyceride to soybean oil from 1:4 to 3:2, whereas the encapsulation efficiency of doxorubicin is slightly reduced from 79.2% ± 2.1% to 71.2% ± 2.9%. The PEGylation of LNE by 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(PEG)2000] (DSPE-PEG 2000) does not significantly change the size and drug encapsulation efficiency. Three-month storage at room temperature and lyophilization process does not affect the drug encapsulation efficiency, whereas the size slightly increases to almost 100 nm. The in-vitro drug-release profiles of LNEs suggest that the present formulation can prolong drug release for 48 hours. LNEs can be internalized into tumor cells in vitro and efficiently accumulate in tumor tissues in vivo by passive targeting. Analysis results of in-vitro and in-vivo antitumor activities reveal that doxorubicin-loaded LNE exerts a therapeutic effect similar to that of the commercial Adriamycin. Moreover, the toxicity of doxorubicin, particularly its cardiac toxicity, is reduced.Conclusion The present LNE formulation of doxorubicin can effectively suppress tumor growth and improve the safety of Adriamycin.
研究领域:
药剂学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2021
·
IF 10.588
Bin Xia,Qi Sui,Yushan Du,Liang Wang,Jing Jing,Lin Zhu,Xinguo Zhao,Xuemei Sun,Andy M. Booth,Bijuan Chen,Keming Qu,Baoshan Xing
Irregular-shaped and partially degraded secondary microplastics (SMP) account for the majority of MPs in marine environments, yet little is known about their effects on marine organisms. In this study, we investigated the embryotoxicity of polyvinyl chloride SMP and primary microplastics (PMP) to the marine medaka Oryzias melastigma . This study aimed to determine the physical impacts of MPs and, for the first time, elucidate the underlying mechanisms of physical toxicity. SMP shortened hatching time and induced higher teratogenic effects on larvae relative to PMP, indicating a higher toxicity from SMP. Physical damage from SMP to the chorion surface appears to be the main toxicity mechanism, caused by their irregular shape and reduced aggregation relative to PMP. In contrast, real-time changes in oxygen demonstrated that hypoxia caused by greater PMP adsorption to the chorion surface contributes to the toxicological responses of this material relative to SMP. Modulation of genes involved in hypoxia-response, cardiac development and hatching confirmed the toxicity mechanisms of PMP and SMP. The chemical contribution to observed toxicity was negligible, confirming impacts derived from physical toxicity. Our findings highlight the negative effects of environmentally relevant SMP on the marine ecosystems .
研究领域:
环境科学
·
毒理学
·
生态学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ENTOMOLOGICAL SCIENCE
·
2023
·Vol. 58
·期 3
·355-369
·
IF 0.9
Gao Shanshan,Guo Mengyi,Yin Yang,Zhang Xinyi,Zhang Yonglei,Zhang Kunpeng
Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) is one of the most destructive pests of stored products. Although there have been studies on the potential use of essential oils from plants in the Artemisia genus as insecticides, no comprehensive bioactivity data are available on the efficacy of Artemisia vulgaris L. (Asterales: Asteraceae) essential oil and its chemical constituents on stored-product pests. Therefore, in this study, the bioactivity of A. vulgaris essential oil and its chemical constituents, eugenol and terpinen-4-ol, against T. castaneum were determined by contact, fumigant, and repellent bioassays. Analysis of contact and fumigant bioassays showed that A. vulgaris essential oil, eugenol, and terpinen-4-ol have contact and fumigant toxicities against T. castaneum , of which terpinen-4-ol has a strong killing effect on larvae and adults, suggesting that terpinen-4-ol may be the main active component of A. vulgaris essential oil in contact and fumigant effects. Additionally, A. vulgaris essential oil and eugenol have higher repellent activity against T. castaneum larvae and adults, whereas the repellent activity of terpinen-4-ol is low, indicating that the main component of A. vulgaris essential oil in repellence may be eugenol. These results further provide relevant theoretical basis for the development of plant essential oil pesticides.
研究领域:
昆虫学
·
植物化学
·
害虫管理
✓ 已验证
产品关联
DOI
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Jinfeng He,Hongyan Liu,Zemeng Li,Minhua Xu,Yong Zhang,Tiemin Jiang,Lingyun Mo
Dichloroacetonitrile (DCAN), an emerged nitrogenous disinfection by-product (N-DBP) in drinking water, has garnered attention owing to its strong cytotoxicity, genotoxicity, and carcinogenicity. However, there are limited studies on its potential hepatotoxicity mechanisms. Understanding hepatotoxicity is essential in order to identify and assess the potential risks posed by environmental pollutants on liver health and to safeguard public health. Here, we investigated the viability, reactive oxygen species (ROS) levels, and cell cycle profile of DCAN-exposed HepG2 cells and analyzed the mechanism of DCAN-induced hepatotoxicity using both transcriptomic and metabolomic techniques. The study revealed that there was a decrease in cell viability, increase in ROS production, and increase in the number of cells in the G2/M phase with an increase in the concentration of DCAN. Omics analyses showed that DCAN exposure increased cellular ROS levels, leading to oxidative damage in hepatocytes, which further induced DNA damage, cell cycle arrest, and cell growth impairment. Thus, DCAN has significant toxic effects on hepatocytes. Integrated analysis of transcriptomics and metabolomics offers new insights into the mechanisms of DCAN-induced hepatoxicity.
研究领域:
毒理学
·
分子生物学
·
环境科学
·
公共卫生
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）