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ENVIRONMENTAL TOXICOLOGY · 2013 ·Vol. 29 ·期 12 ·1460-1470 · IF 2.708

Biochemical biomarkers in liver and gill tissues of freshwater fish Carassius auratus following in vivo exposure to hexabromobenzene

Mingbao Feng,Ruijuan Qu,Ying Li,Zhongbo Wei,Zunyao Wang

Hexabromobenzene (HBB) is a novel brominated flame retardant (BFR) with ample evidence of its ubiquitous existence in the aquatic ecosystems. However, to date, the toxicological effects of this BFR on fish have been inadequately researched. The present study was conducted, based on an in vivo model, to investigate HBB-induced biochemical changes in liver and gill tissues of Carassius auratus after medium-term exposure to different concentrations (10, 150, and 300 mg/kg) for 7, 14, and 25 days. Oxidative stress was evoked evidently for the prolonged exposure, demonstrated by significant inhibition in antioxidant enzymes activities including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and glutathione S-transferase, and a decrease in reduced glutathione level, as well as simultaneous elevation in malondialdehyde content. Moreover, Na + , K + -ATPase activity, and protein level were remarkably reduced in fish tissues. Based on the integrated biomarker response, the toxic potency in each treatment was distinguished, and the more severe stress was mainly noted with the increasing concentrations and the extending durations. It was also observed that liver exhibited more pronounced alterations in biochemical parameters than gill, probably indicating the vulnerability of liver to HBB-triggered oxidative stress. Taken together, the results of this study clearly showed that HBB was capable of inducing oxidative stress and inhibiting Na + , K + -ATPase activity in different tissues of C. auratus after medium-term exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1460–1470, 2014.

CAS / MDL: 87-82-1
研究领域: 环境毒理学 · 水生生态学 · 生物化学
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TOXICOLOGY LETTERS · 2021 · IF 4.374

The disruption and hyperpermeability of blood-labyrinth barrier mediates cisplatin-induced ototoxicity

Jiayi Gu,Ling Tong,Xin Lin,Yuming Chen,Hao Wu,Xueling Wang,Dehong Yu

The ototoxic mechanisms of cisplatin on the organ of Corti and spiral ganglion neurons have been extensively studied, while few studies have been focused on the stria vascularis (SV). Herein, we verified the functional and morphological impairment in SV induced by a single injection of cisplatin (12 mg/kg, I.P.), represented by a reduction in Endocochlear Potentials (EP) and strial atrophy, and explored underlying mechanisms. Our results revealed increased extravasation of chromatic tracers (Evans blue dye and FITC-dextran) around microvessels after cisplatin exposure. The increased vascular permeability could be attributed to changes of pericytes (PCs) and perivascular-resident macrophage-like melanocytes (PVM/Ms) in number or morphology, as well as the enhanced level of HIF-1α and downstream VEGF. This capillary leakage led to a high accumulation of cisplatin in the perivascular space in SV, and disrupted the integrity of blood-labyrinth barrier (BLB). Also, tight junction (ZO-1) loosening and Na + , K + -ATPase damage was considered to be other critical contributors of BLB breakdown, which resulted in EP drop and consequent hearing loss. This study explored the role of stria vascularis in cisplatin-induced ototoxicity in terms of BLB hyperpermeability and pointed to a novel therapeutic target for the prevention of cisplatin-related hearing loss.

CAS / MDL: 14913-33-8
研究领域: 耳鼻喉科学 · 药理学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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PHYSIOLOGIA PLANTARUM · 2018 ·Vol. 165 ·期 2 ·155-168 · IF 2.58

Comparative physiological analysis in the tolerance to salinity and drought individual and combination in two cotton genotypes with contrasting salt tolerance

Wasim Ibrahim,Cheng-Wei Qiu,Can Zhang,Fangbin Cao,Zhu Shuijin,Feibo Wu

Soil salinity and drought are the two most common and frequently co-occurring abiotic stresses limiting cotton growth and productivity. However, physiological mechanisms of tolerance to such condition remain elusive. Greenhouse pot experiments were performed to study genotypic differences in response to single drought (4% soil moisture; D) and salinity (200 mM NaCl; S) stress and combined stresses (D + S) using two cotton genotypes Zhongmian 23 (salt-tolerant) and Zhongmian 41 (salt-sensitive). Our results showed that drought and salinity stresses, alone or in combination, caused significant reduction in plant growth, chlorophyll content and photosynthesis in the two cotton genotypes, with the largest impact visible under combined stress. Interestingly, Zhongmian 23 was more tolerant than Zhongmian 41 under the three stresses and displayed higher plant dry weight, photosynthesis and antioxidant enzymes activities such as superoxide dismutase (SOD), peroxidase (POD) catalase (CAT) and ascorbate peroxidase (APX) activities compared to control, while those parameters were significantly decreased in salt-stresses Zhongmian 41 compared to control. Moreover, Na + /K + -ATPase activity was more enhanced in Zhongmian 23 than in Zhongmian 41 under salinity stress. However, under single drought stress and D + S stress no significant differences were observed between the two genotypes. No significant differences were detected in Ca 2+ /Mg 2+ -ATPase activity in Zhongmian 41, while in Zhongmian 23 it was increased under salinity stress. Furthermore, Zhongmian 23 accumulated more soluble sugar, glycine-betaine and K + , but less Na + under the three stresses compared with Zhongmian 41. Obvious changes in leaf and root tips cell ultrastructure was observed in the two cotton genotypes. However, Zhongmian 23 was less affected than Zhongmian 41 especially under salinity stress. These results give a novel insight into the mechanisms of single and combined effects of drought and salinity stresses on cotton genotypes.

研究领域: 植物生理学 · 农学 · 胁迫生物学
✓ 已验证 DOI PubMed 高影响因子
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Probiotics and Antimicrobial Proteins · 2022 ·Vol. 15 ·期 2 ·400-410 · IF 5.265

Antimicrobial Substances and Mechanisms of Lactobacillus rhamnosus against Gardnerella vaginalis

Huang Yu-Ping,Shi Jie-Yan,Luo Si-Chen,Xu Shao-Yan,Zhang Jia-Dong,Molnár István,Yang Qiong-Qiong,Zhang Bo-Bo

Bacterial vaginosis (BV) is a common vaginal disease associated with abnormal changes in the vaginal microbiome. Our previous study found that Lactobacillus rhamnosus has a good therapeutic effect on bacterial vaginosis by inhibiting the most prominent bacterium associated with BV, Gardnerella vaginalis . In this study, we show that acetic acid and lactic acid are the main substances in the cell-free supernatant (CFS) of L. rhamnosus that inhibit the growth of G. vaginalis. Further study on the mechanism showed that acetic acid and lactic acid alter the morphology of the G. vaginalis cells, eventually causing the cells to shrink or burst, resulting in exudation of their intracellular contents. In addition, these two organic acids also dissipate the membrane potential of bacterial cells, affecting their synthesis of ATP. A reduced activity of the Na + /K + -ATPase leads to abnormal ATP metabolism, and ultimately inhibits the growth and reproduction of G. vaginalis . Our study provides valuable information for the widespread application of L. rhamnosus in the treatment of bacterial vaginosis.

研究领域: 微生物学 · 传染病 · 女性健康
✓ 已验证 DOI PubMed 高影响因子
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ENVIRONMENTAL SCIENCE & TECHNOLOGY · 2016 · IF 5.393

New Insights into the Cytotoxic Mechanism of Hexabromocyclododecane from a Metabolomic Approach

Feidi Wang,Haijun Zhang,Ningbo Geng,Baoqin Zhang,Xiaoqian Ren,Jiping Chen

The toxic effects of hexabromocyclododecane (HBCD) are complex, and the underlying toxicological mechanisms are still not completely understood. In this study, a pseudotargeted metabolomic approach based on the UHPLC/Q-Trap MS system was developed to assess the HBCD-intervention-related metabolic alteration in HepG2 cells. In addition, some physiologic indicators and relevant enzyme activities were measured. HBCD exposure obviously impaired metabolic homeostasis and induced oxidative stress, even at an environmentally relevant dose (0.05 mg/L). Metabolic profiling and multivariate analysis indicated that the main metabolic pathways perturbed by HBCD included amino acid metabolism, protein biosynthesis, fatty acid metabolism, and phospholipid metabolism. HBCD suppressed the cell uptake of amino acids, mainly through inhibition of the activity of membrane transport protein Na+/K+-ATPase. HBCD down-regulated glycolysis and β-oxidation of long-chain fatty acids, causing a large decrease of ATP production. As a result, the across-membrane transport of amino acids was further inhibited. Meanwhile, HBCD induced a significant increase of total phospholipids, mainly through the remodeling of phospholipids from the increased free fatty acids. The obtained metabolomic results also provided some new evidence and clues regarding the toxicological mechanisms of HBCD that contribute to obesity, diabetes, nervous system damage, and developmental disorders.

研究领域: 毒理学 · 细胞生物学 · 代谢组学 · 环境科学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF INORGANIC BIOCHEMISTRY · 2022 · IF 4.336

Synthesis of phytonic silver nanoparticles as bacterial and ATP energy silencer

Liting Huang,Renxiang Chen,Jieer Luo,Murtaza Hasan,Xugang Shu

Recently, silver nanoparticles have been widely applied in various fields as inorganic antimicrobial agents. This present study adopted a facile, environmentally friendly and cost-effective method to green synthesized silver nanoparticles via the extract of Dioscorea cirrhosa tuber (DCTE-Ag NPs). Green synthesized Ag nanoparticles were characterized by using the transmission electron microscope , X-ray diffraction analysis (XRD), UV–visible spectroscopy (UV–Vis), fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), etc. The results authenticate that the green synthesized Ag NPs were spherical in shape with an average size of 13.87 ± 2.38 nm and have crystalline properties. According to the antibacterial test, the average width of the inhibition zone of green synthesized Ag NPs against Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ) were 14.17 ± 0.84 mm and 13.01 ± 0.72 mm, respectively. The antibacterial property of Ag NPs was further evaluated by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), and the results indicated that they exhibited outstanding antimicrobial activity . Besides, DCTE-Ag NPs has the good bacteriostasis function, which can damage bacterial cells membrane to leak the intracellular contents and inhibit the activity of Na + /K + -ATP-ase to hinder energy conversion.

CAS / MDL: 7761-88-8
研究领域: 纳米技术 · 材料科学 · 微生物学 · 药学 · 环境科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2021 · IF 7.963

Physiological and transcriptomic analyses reveal the toxicological mechanism and risk assessment of environmentally-relevant waterborne tetracycline exposure on the gills of tilapia (Oreochromis niloticus)

Yi-Chuang Xu,Guang-Hui Liu,Yi-Huan Xu,Tao Zhao,Hua Zheng,Xiao-Ying Tan

With the increasing application of tetracycline (TC) in medical treatment, animal husbandry and aquaculture in recent decades, high quantities of TC have been frequently detected in the aquatic environment, and accordingly TC-related toxicity and environmental pollution have become a global concern. The present study was performed to explore the toxicological influences of TC exposure at its environmentally relevant concentrations on the gills of tilapia Oreochromis niloticus , based on the alteration in histopathology, oxidative stress, inflammatory response, cell cycle, mitochondrial function, apoptosis, and transcriptomic analysis. Our findings revealed that TC exposure damaged the structure and function, induced oxidative stress, affected inflammatory responses, and reduced Na + /K + -ATPase (NKA) activity in the gills. TC also caused the inhibition in cell cycle, resulted in mitochondrial dysfunction and activated apoptosis. Further transcriptomic analysis indicated the extensive influences of TC exposure on the gill function, and immune system was the main target to waterborne TC exposure. These results elucidated that environmental TC had more complex toxicological effects on gills of fish than previously assessed, and provided novel insight into molecular toxicology of TC on fish and good basis for assessing the environmental risk of TC.

CAS / MDL: 64-75-5
研究领域: 环境毒理学 · 水生毒理学 · 分子生物学 · 转录组学 · 鱼类生理学
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2023 ·Vol. 24 ·期 16 ·12934 · IF 5.6

Single and Combined Effects of Chlorpyrifos and Glyphosate on the Brain of Common Carp: Based on Biochemical and Molecular Perspective

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

CAS / MDL: 2921-88-2
研究领域: 环境毒理学 · 分子生物学 · 神经科学 · 水生毒理学
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Oncotarget · 2016 · IF 5.008

Octreotide-periplocymarin conjugate prodrug for improving targetability and anti-tumor efficiency: synthesis, in vitro and in vivo evaluation

Hui-Yun Zhang,Wen-Qian Xu,Yuan-yuan Zheng,Emmanuel Omari-Siaw,Yuan Zhu,Xia Cao,Shan-Shan Tong,Jiang-nan Yu,Xi-ming Xu

Cardiac glycosides could increase intracellular Ca 2+ ion by inhibiting the Na + /K + ATPase to induce apoptosis in many tumor cells. However, narrow therapeutic index, poor tumor selectivity and severe cardiovascular toxicity hinder their applications in cancer treatment. To improve the safety profile and tumor targetablility of cardiac glycosides, we designed octreotide conjugated periplocymarin, a cardiac glycoside isolated from Cortex periplocae . The conjugate showed higher cytotoxicity on MCF-7 cells and HepG2 tumor cells (SSTRs overexpression) but much less toxicity in L-02 normal cells. Tissue distribution studies of the conjugate using H 22 tumor model in mice showed higher accumulation in tumor and lower distribution in heart and liver than periplocymarin. Furthermore, in vivo anticancer effects of the conjugate on mice bearing H 22 cancer xenografts confirmed enhanced anti-tumor efficacy and decreased systemic toxicity. Altogether, octreotide-conjugated periplocymarin demonstrated tumor selectivity and may be useful as a targeting agent to improve the safety profile of cardiac glycosides for cancer therapy.

研究领域: 药理学 · 肿瘤学 · 药物递送系统 · 药物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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MOLECULES · 2019 ·Vol. 24 ·期 12 ·2266 · IF 3.06

Mechanism Investigation of Tagetes patula L. against Chronic Nonbacterial Prostatitis by Metabolomics and Network Pharmacology

Xueying Liu,Xiaoku Ran,Muhammad Riaz,Haixue Kuang,Deqiang Dou,Decheng Cai

The major objective of this study was to investigate the anti-chronic nonbacterial prostatitis (CNP) mechanism ofT. patulaby metabolomics and network pharmacology. The study demonstrated that the flavonoids and polysaccharides ofT. patulacould alleviate prostatitis by improving the level of DHT, reducing the secretion of PSA and TNF-α. Besides, both could enhance Na+/K+-ATPase activity, decrease the O2consumption, CO2production, heat production, energy expenditure of rats and promote respiratory exchange ratio of rats. Up to 28 potential biomarkers and 8 key metabolic pathways related to the treatment of CNP were elucidated by the metabolomics analysis, including phenylalanine metabolism, taurine and hypotaurine metabolism, tryptophan metabolism etc. Network pharmacology prediction also reflected the potential mechanism was associated with tryptophan metabolism and energy pathway. Generally, the potential anti-CNP mechanism of flavonoids and polysaccharides ofT. patulamight be through reducing the expression of inflammation factors, adjusting the level of hormone and regulating the amino acid metabolism, energy metabolism and glucose and lipid metabolism.Keywords:Tagetes patulaL.;chronic nonbacterial prostatitis;metabolomics;energy metabolism;network pharmacology

研究领域: 药理学 · 代谢组学 · 传统医学 · 前列腺疾病
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