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1.
Environ Res ; 231(Pt 2): 116177, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37201707

RESUMO

In this work, a new dendrimer modified magnetic graphene oxide (GO) was used as a substrate for electrodeposition of Au nanoparticles. The modified magnetic electrode was employed for sensitive measuring of As(III) ion as a well-established human carcinogen. The prepared electrochemical device exhibits excellent activity towards As(III) detection using the square wave anodic stripping voltammetry (SWASV) protocol. At optimum conditions (deposition potential at -0.5 V for 100 s in 0.1 M acetate buffer with pH 5.0), a linear range from 1.0 to 125.0 µgL-1 with a low detection limit (calculated by S/N = 3) of 0.47 µg L-1 was obtained. In addition to the simplicity and sensitivity of the proposed sensor, its high selectivity against some major interfering agents, such as Cu(II) and Hg(II) makes it an appreciable sensing tool for the screening of As(III). In addition, the sensor revealed satisfactory results for detection of As(III) in different water samples, and the accuracy of obtained data were confirmed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) setup. Accounting for the high sensitivity, remarkable selectivity and good reproducibility, the established electrochemical strategy has great potential for analysis of As(III) in environmental matrices.


Assuntos
Ouro , Nanopartículas Metálicas , Humanos , Ouro/química , Reprodutibilidade dos Testes , Nanopartículas Metálicas/química , Fenômenos Magnéticos
2.
Drug Chem Toxicol ; 45(6): 2411-2423, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34315305

RESUMO

Curcumin (Cur) is a flavonoid derived from Curcuma longa L. that has been shown to have a variety of biological activities, but some previous studies have described its non-negligible negative effects on female reproduction and embryo development. To further explore the toxic stress effect, this study investigated apoptosis and autophagy of healthy buffalo (Bubalus bubalis) derived granulosa cells (GCs) exposed to Cur and/or autophagy inhibitors. Results showed that Cur declined viability of GCs in a concentration-dependent manner. Apoptosis was observed in Cur-treated GCs from 3 h. Meanwhile, under Cur stress, autophagosomes accumulated in cells, and the expression levels of autophagy key proteins LC3 and Beclin 1 were up-regulated, suggesting that Cur could induce autophagy in GCs. Early autophagy inhibitor 3-methyladenine (3-MA) increased the apoptosis rate of Cur exposed GCs, but the autophagosome degradation inhibitor chloroquine (CQ) had no effect on the apoptosis rate. The network pharmacological and molecular docking analysis indicated that the perturbation of IKK/NF-κB might be the cause of Cur toxicity toward GCs. This study unveiled another side of Cur pharmacological effects that programmed cell death can be induced by Cur in GCs, suggesting that it should be prudent to use Cur as a clinical drug for its side effects on the female reproductive system.


Assuntos
Curcumina , Feminino , Animais , Curcumina/toxicidade , Simulação de Acoplamento Molecular , Proteína Beclina-1/farmacologia , NF-kappa B , Farmacologia em Rede , Autofagia , Apoptose , Células da Granulosa/metabolismo , Flavonoides/farmacologia , Cloroquina/toxicidade
3.
Mar Drugs ; 19(5)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922488

RESUMO

This work aimed to investigate the effect of fucoidan (FPS) on urate transporters induced by uric acid (UA). The results showed that UA stimulated the expression of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) in HK-2 cells, and FPS could reverse the effect. Moreover, UA could activate NF-κB, JNK and PI3K/Akt pathways, but both pathway inhibitors and FPS inhibited the UA-induced activation of these three pathways. These data suggested that FPS effectively inhibited the expression induction of reabsorption transporters URAT1 and GLUT9 by UA, through repressing the activation of NF-κB, JNK and PI3K/Akt signal pathways in HK-2 cells. The in vitro research findings support the in vivo results that FPS reduces serum uric acid content in hyperuricemia mice and rats through inhibiting the expression of URAT1 and GLUT9 in renal tubular epithelial cells. This study provides a theoretical basis for the application of FPS in the treatment of hyperuricemia.


Assuntos
Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Supressores da Gota/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Laminaria , NF-kappa B/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular , Supressores da Gota/isolamento & purificação , Humanos , Túbulos Renais Proximais/enzimologia , Laminaria/química , Polissacarídeos/isolamento & purificação , Transdução de Sinais , Ácido Úrico/toxicidade
4.
Molecules ; 26(2)2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33467083

RESUMO

Chitosan is the only cationic polysaccharide found in nature. It has broad application prospects in biomaterials, but its application is limited due to its poor solubility in water. A novel chitosan derivative was synthesized by amidation of chitosan with 18ß-glycyrrhetinic acid and sialic acid. The chitosan derivatives were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and measurement of the zeta potential. We also investigated the solubility, cytotoxicity, and blood compatibility of chitosan derivatives. 18ß-glycyrrhetinic acid and sialic acid could be grafted onto chitosan molecular chains. The thermal stability of the synthesized chitosan derivatives was decreased and the surface was positively charged in water and phosphate-buffered saline. After chitosan had been modified by 18 ß-glycyrrhetinic acid and sialic acid, the solubility of chitosan was improved greatly in water and phosphate-buffered saline, and percent hemolysis was <5%. Novel amphiphilic chitosan derivatives could be suitable polymers for biomedical purposes.


Assuntos
Quitosana , Ácido Glicirretínico/análogos & derivados , Teste de Materiais , Ácido N-Acetilneuramínico , Linhagem Celular , Quitosana/análogos & derivados , Quitosana/síntese química , Quitosana/química , Quitosana/farmacologia , Ácido Glicirretínico/química , Ácido Glicirretínico/farmacologia , Humanos , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/farmacologia , Solubilidade
5.
Mar Drugs ; 18(8)2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32707775

RESUMO

Fucoidan-a marine natural active polysaccharide derived from brown algae with a variety of medicinal activities and low toxicity-has been used as clinical drug for renal diseases for nearly 20 years. The pharmacological mechanism of fucoidan has been well-investigated, based on target molecules and downstream signaling pathways. This review summarizes some important molecular targets of fucoidan and its related biologic activities, including scavenger receptor (SR), Toll-like receptors (TLRs), C-type lectin (CLEC) and some newly found target molecules, which may be beneficial for further understanding the pharmacological mechanism of fucoidan and discovering its new functions, as well as developing related clinical or adjuvant drugs and functional preparations.


Assuntos
Phaeophyceae/química , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Humanos , Polissacarídeos/isolamento & purificação
6.
Mar Drugs ; 18(8)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32731522

RESUMO

Saccharomyces cerevisiae was used as a model to explore the preventive effect of two marine polysaccharides separately derived from Sepia esculenta ink (SIP) and Laminaria japonica (FL) as well as one terrestrial polysaccharides from Eleocharis tuberosa peel (WCPP) on toxic injury induced by acrylamide (AA). The growth of yeast was evaluated by kinetics indexes including doubling time, lag phase and maximum proliferation density. Meanwhile, intracellular redox state was determined by contents of MDA and GSH, and SOD activity. The results showed that AA inhibited yeast growth and destroyed the antioxidant defense system. Supplement with polysaccharides, the oxidative damage of cells was alleviated. According to the growth recovery of yeast, FL and WCPP had similar degree of capacity against AA associated cytotoxicity, while SIP was 1.5~2 folds as strong as FL and WCPP. SIP and FL significantly reduced production of MDA by AA administration. Moreover, SIP, FL and WCPP increased SOD activity and repressed GSH depletion caused by AA.


Assuntos
Acrilamida/toxicidade , Antioxidantes/farmacologia , Eleocharis/química , Laminaria/química , Estresse Oxidativo/efeitos dos fármacos , Polissacarídeos/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Sepia/química , Animais , Antioxidantes/isolamento & purificação , Glutationa/metabolismo , Tinta , Cinética , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Oxirredução , Polissacarídeos/isolamento & purificação , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Superóxido Dismutase/metabolismo
7.
Mar Drugs ; 17(11)2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31683929

RESUMO

To investigate the effect of carboxymethylation and phosphorylation modification on Sepia esculenta ink polysaccharide (SIP) properties, this study prepared carboxymethyl SIP (CSIP) with the chloracetic acid method, and phosphorylated SIP (PSIP) with the sodium trimetaphosphate (STMP)/sodium tripolyphosphate (STPP) method, on the basis of an orthogonal experiment. The in vitro antioxidant and anticoagulant activities of the derivatives were determined by assessing the scavenging capacity of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals, which activated the partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). The results showed that SIP was modified successfully to be CSIP and PSIP, and degrees of substitution (DSs) of the two products were 0.9913 and 0.0828, respectively. Phosphorylation efficiently improved the antioxidant property of SIP, and the IC50 values of PSIP on DPPH and hydroxyl radicals decreased by 63.25% and 13.77%, respectively. But carboxymethylation reduced antioxidant activity of the native polysaccharide, IC50 values of CSIP on the DPPH and hydroxyl radicals increased by 16.74% and 6.89%, respectively. SIP significantly prolonged the APTT, PT, and TT in a dose-dependent fashion, suggesting that SIP played an anticoagulant action through intrinsic, extrinsic, and common coagulation pathways. CSIP and PSIP both possessed a stronger anticoagulant capacity than SIP via the same pathways; moreover, CSIP was observed to be more effective in prolonging APTT and PT than PSIP.


Assuntos
Metilação , Fosforilação , Polissacarídeos/química , Polissacarídeos/metabolismo , Animais , Anticoagulantes/química , Antioxidantes/química , Masculino , Camundongos , Fosforilação/fisiologia , Sepia/química
8.
Molecules ; 24(14)2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315269

RESUMO

Mussel adhesive proteins (MAPs) have a unique ability to firmly adhere to different surfaces in aqueous environments via the special amino acid, 3,4-dihydroxyphenylalanine (DOPA). The catechol groups in DOPA are a key group for adhesive proteins, which is highly informative for the biomedical domain. By simulating MAPs, medical products can be developed for tissue adhesion, drug delivery, and wound healing. Hydrogel is a common formulation that is highly adaptable to numerous medical applications. Based on a discussion of the adhesion mechanism of MAPs, this paper reviews the formation and adhesion mechanism of catechol-functionalized hydrogels, types of hydrogels and main factors affecting adhesion, and medical applications of hydrogels, and future the development of catechol-functionalized hydrogels.


Assuntos
Bivalves/química , Catecóis/química , Animais , Bivalves/metabolismo , Di-Hidroxifenilalanina/química , Sistemas de Liberação de Medicamentos , Hidrogéis , Proteínas/metabolismo , Aderências Teciduais , Cicatrização
9.
Mar Drugs ; 16(4)2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29597272

RESUMO

Sepia ink polysaccharide (SIP) isolated from squid and cuttlefish ink is a kind of acid mucopolysaccharide that has been identified in three types of primary structures from squid (Illex argentinus and Ommastrephes bartrami), cuttlefish Sepiella maindroni, and cuttlefish Sepia esculenta ink. Although SIP has been proved to be multifaceted, most of the reported evidence has illuminated its chemopreventive and antineoplastic activities. As a natural product playing a role in cancer treatment, SIP may be used as chemotherapeutic ancillary agent or functional food. Based on the current findings on SIP, we have summarized four topics in this review, including: chemopreventive, antineoplastic, chemosensitive, and procoagulant and anticoagulant activities, which are correlative closely with the actions of anticancer agents on cancer patients, such as anticancer, toxicity and thrombogenesis, with the latter two actions being common causes of death in cancer cases exposed to chemotherapeutic agents.


Assuntos
Tinta , Polissacarídeos/química , Sepia/química , Animais , Quimioterapia Adjuvante
10.
Mar Drugs ; 16(12)2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30486413

RESUMO

This work aims to explore the amelioration of fucoidan on adenine-induced hyperuricemia and hepatorental damage. Adenine-induced hyperuricemic mice were administered with fucoidan, allopurinol and vehicle control respectively to compare the effects of the drugs. Serum uric acid, urea nitrogen, hepatorenal functions, activities of hepatic adenosine deaminase (ADA), xanthine oxidase (XOD), renal urate transporter 1 (URAT1) and NF-κB p65 were assessed. As the serum uric acid, urea nitrogen, creatinine, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) data demonstrated, the adenine not only mediated hepatorenal function disorders, but also induced hyperuricemia in mice. Meanwhile, activities of hepatic ADA and XOD were markedly augmented by adenine, and the expression of URAT1 was promoted, which was conducive to the reabsorption of urate. However, exposure to fucoidan completely reversed those adenine-induced negative alternations in mice, and the activities of hepatic ADA and XOD were recovered to the normal level. It was obvious that hepatic and renal functions were protected by fucoidan treatment. The expression of URAT1 was returned to normal, resulting in an increase of renal urate excretion and consequent healing of adenine-induced hyperuricemia in mice. Expression and activation of NF-κB p65 was promoted in kidneys of adenine treated mice, but suppressed in kidneys of mice exposed to fucoidan from Laminaria japonica or allopurinol. In conclusion, the fucoidan is a potential therapeutic agent for the treatment of hyperuricemia through dual regulatory roles on inhibition of hepatic metabolism and promotion of renal excretion of urate.


Assuntos
Hiperuricemia/tratamento farmacológico , Laminaria/química , Polissacarídeos/farmacologia , Eliminação Renal/efeitos dos fármacos , Ácido Úrico/metabolismo , Adenina/toxicidade , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Creatinina/urina , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Hiperuricemia/induzido quimicamente , Hiperuricemia/urina , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Polissacarídeos/isolamento & purificação , Polissacarídeos/uso terapêutico , Resultado do Tratamento , Ácido Úrico/sangue , Ácido Úrico/urina
11.
Pak J Pharm Sci ; 31(1): 25-29, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29348080

RESUMO

The present study was conducted to investigate the preventive effects of squid ink polysaccharides (SIP) on the damage of sperm and reproduction induced by cyclophosphamide that is most commonly used for treating clinically cancers. Male Kunming mice exposed to cyclophosphamide were administered with SIP and were sacrificed to determine sperm parameters, testicular antioxidant ability and reproductive capacity. Data indicated that cyclophosphamide caused obvious changes in mice such as significant reduction (P<0.01) of glutathione reductase activity (GR), vitamin C (Vc) content and total antioxidant capacity (T-AOC) in the testes, as well as elevation (P<0.01) of abnormal rates of sperm and fetus, and a decrease in the total fetal count and average fetal count (P<0.01), were totally alleviated by SIP. From these findings it can be concluded that SIP decreases chemotherapeutic damage to sperm and reproduction in mice induced by cyclophosphamide.


Assuntos
Antineoplásicos Alquilantes/efeitos adversos , Antioxidantes/farmacologia , Ciclofosfamida/efeitos adversos , Decapodiformes/química , Polissacarídeos/farmacologia , Testículo/efeitos dos fármacos , Animais , Antioxidantes/isolamento & purificação , Líquidos Corporais/química , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos , Estresse Oxidativo/efeitos dos fármacos , Exposição Paterna , Polissacarídeos/isolamento & purificação , Reprodução/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia
12.
J Ethnopharmacol ; 335: 118614, 2024 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-39053708

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hyperuricemia is a common metabolic disease with prominent morbidity, it can lead to many adverse effects and complications, such as chronic nephrosis. Fucoidan has been used as natural drug for acute and chronic kidney disease for over 20 years in China, but the precise mechanisms underlying the renal protective function are still indefinable. PURPOSE: This study is conducted to explore alleviation of fucoidan (FPS) from Laminaria japonica on urate-induced NOD-like receptor family, pyrin domain-containing 3 (NLRP3)-mediated pyroptosis in renal tubular epithelial cells HK-2, as well as the mechanism of nuclear factor κB (NF-κB) signaling pathway involved. MATERIALS AND METHODS: HK-2 cells were treated with FPS, uric acid (UA), and inhibitor of NF-κB signaling pathway. Nitric oxide (NO) content and inducible nitric oxide synthase (iNOS) activity were determined with detection kits. Activation of intercellular NLRP3 inflammasome and NF-κB signaling pathway, gasdermin D (GSDMD) expression level were evaluated with Western blot and quantitative reverse transcription-PCR (qRT-PCR), and immunofluorescent analysis. RESULTS: Data showed that UA induced cellular inflammatory response demonstrated by elevated NO content, iNOS activity and expression level of NLRP3 inflammasome-mediated pyroptosis associated molecules including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), Caspase-1, interleukin 18 (IL-18) and GSDMD, moreover the NF-κB signaling pathway was activated by UA. However, FPS exposure inhibited efficiently the UA induced adverse effect. CONCLUSION: It can be concluded that FPS inhibited UA-induced NLRP3-mediated pyroptosis in HK-2 cells through repressing NF-κB signaling pathway.


Assuntos
Células Epiteliais , Túbulos Renais , Laminaria , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Polissacarídeos , Piroptose , Transdução de Sinais , Ácido Úrico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/efeitos dos fármacos , NF-kappa B/metabolismo , Humanos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Linhagem Celular , Laminaria/química , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/citologia , Túbulos Renais/metabolismo , Algas Comestíveis
13.
Int J Biol Macromol ; 254(Pt 3): 128029, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37952330

RESUMO

Four main water-soluble wampee fruit pulp polysaccharides, named CSP-I, CSP-II, CSP-III and CSP-IV, were isolated from Clausena lansium (Lour.) Skeels Guifei, therein CSP-IV content was higher than the others. All components possess certain anticoagulant activity demonstrated by prolonged activated partial thromboplastin time, especially CSP-IV, which suggests that CSP-IV plays anticoagulant effect through disturbing intrinsic coagulation pathway. The wampee polysaccharide CSP-IV with Mw of 510.1 kDa was mainly composed of Gal, Ara and GalA. Backbone of CSP-IV contains Gal, Ara and GalA, two kinds of side chains contain one monosaccharide Gal or Ara, both branch on Gal residue of backbone. CSP-IV has no the conformation of triple helix demonstrated by Congo red test. These results showed that CSP-IV is an acidic polysaccharide with potential anticoagulant activity via targeting intrinsic coagulation pathway.


Assuntos
Clausena , Frutas , Frutas/química , Água/análise , Polissacarídeos/química , Anticoagulantes/farmacologia
14.
J Mol Biol ; 436(22): 168781, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39245319

RESUMO

Ubiquitination is a common post-translational modification of proteins in eukaryotic cells, and it is also a significant method of regulating protein biological function. Computational methods for predicting ubiquitination sites can serve as a cost-effective and time-saving alternative to experimental methods. Existing computational methods often build classifiers based on protein sequence information, physical and chemical properties of amino acids, evolutionary information, and structural parameters. However, structural information about most proteins cannot be found in existing databases directly. The features of proteins differ among species, and some species have small amounts of ubiquitinated proteins. Therefore, it is necessary to develop species-specific models that can be applied to datasets with small sample sizes. To solve these problems, we propose a species-specific model (SSUbi) based on a capsule network, which integrates proteins' sequence and structural information. In this model, the feature extraction module is composed of two sub-modules that extract multi-dimensional features from sequence and structural information respectively. In the submodule, the convolution operation is used to extract encoding dimension features, and the channel attention mechanism is used to extract feature map dimension features. After integrating the multi-dimensional features from both types of information, the species-specific capsule network further converts the features into capsule vectors and classifies species-specific ubiquitination sites. The experimental results show that SSUbi can effectively improve the prediction performance of species with small sample sizes and outperform other models.

15.
Phys Chem Chem Phys ; 15(11): 3866-80, 2013 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-23399983

RESUMO

The adsorption of formaldehyde (HCHO) on both clean and hydroxylated TiO(2)-B(100) surfaces with terminal and bridging hydroxyl groups is systematically investigated by using first principles density functional theory calculations. The discussion is mainly focused on the two different chemical adsorption configurations of HCHO in periodicity (2 × 2), in which the C atom of HCHO is bonded with two coordinated O atoms on a step (Structure I) or on a terrace (Structure II). The study indicates that bridging hydroxyl groups on most of the adsorption sites near to HCHO will weaken the adsorption of HCHO, while terminal hydroxyl groups on most of adsorption sites will facilitate it. The investigation of the effects of hydroxyl groups and H(2)O molecule on HCHO in different periodicities shows that the terminal hydroxyl groups or H(2)O molecules have significantly facilitated the adsorption of H(2)O at larger periodicities, while bridging hydroxyl groups do not have this trend. The analysis of the adsorption mechanisms of HCHO molecules on both clean and hydroxylated surfaces indicate that the terminal hydroxyl groups can extract electrons from the surface and facilitate adsorption of HCHO due to the adsorption energy being higher than that on the clean surface, while the bridging hydroxyl groups donate electrons to the surface and weaken the adsorption. In all chemical adsorption configurations, HCHO acts as an electron acceptor. Interestingly, though the adsorptions are weaker, HCHO in Structure II gains more electrons on both the clean and hydroxylated surfaces than in Structure I. This unique mechanism provides a novel angle to understand the interaction of HCHO with the hydroxylated TiO(2) surface.

16.
Chemosphere ; 344: 140315, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37769911

RESUMO

BACKGROUND: It has been reported that antibiotic enrofloxacin can impair reproductive function of mammals, induces multi-generational oscillatory effects on reproduction of Caenorhabditis elegans, and disturbes endocrine system in grass carp. OBJECTIVES: This study aims to explore the effect of short-term enrofloxacin exposure on sex steroid hormones biosynthesis in Carassius auratus var. Pengze through assessing the contents of growth hormone (GH), thyroid hormone 4 (T4), estradiol (E2) and testosterone (T) in plasma, and investigating sex steroid hormones biosynthesis based on targeted metabonomics analysis, and determining expression level of some important genes, gonadotropin-releasing hormone (gnrh), gonadotropin hormone 1-ß (gth1-ß), gonadotropin hormone 2-ß (gth2-ß) and cyp19a1a in hypothalamus-pituitary-ovary axis (HPOA). RESULTS: We found that short-term exposure of enrofloxacin disordered contents of E2 and T in plasma of fish determined by ELISA detection, T content elevation and E2 content decline, which was confirmed by the following data from targeted metabonomics analysis of plasma. The metabonomic results showed that both T and its upstream intermediate products during the process of sex steroid hormones biosynthesis in fish were increased significantly, but E2 content was decreased markedly. At the exposure 24 h of enrofloxacin, expression of gnrh in hypothalamus, gth1-ß and gth2-ß in pituitary were promoted. Meanwhile GH and T4 contents in plasma, two inducers of sex steroid hormones synthesis, were augmented, which indicated that sex steroid hormones biosynthesis was improved. However cyp19a1a expression in ovary was repressed, and content of estriol (E3) was upregulated. These data suggested that enrofloxacin promoted sex steroid hormones biosynthesis and conversion of E2 to estriol (E3), but inhibited the conversion of T to E2. Finally, content of E2 was declined sharply. DISCUSSION: Animal specific antibacterial enrofloxacin is widely detectable in aquatic ecosystem, exposure of the agent can induce adverse effects on plants and animals. This study firstly evidenced induction of disruption of sex steroid hormones by enrofloxacin in fish, which indicates enrofloxacin is an endocrine disruption compound that can induce endocrine disruption of animals, including fish.


Assuntos
Antibacterianos , Carpa Dourada , Animais , Feminino , Carpa Dourada/metabolismo , Enrofloxacina , Antibacterianos/toxicidade , Antibacterianos/metabolismo , Ecossistema , Hormônios Esteroides Gonadais/metabolismo , Hormônio do Crescimento/genética , Estradiol/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Gonadotropinas/metabolismo , Estriol , Mamíferos/metabolismo
17.
Sci Total Environ ; 869: 161730, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36681334

RESUMO

To further explore short-term exposure of enrofloxacin (ENR) induced toxicity in crucian carp brain that has been reported by our previous work, as well as the possible toxicological mechanisms, this study investigated the blood-brain barrier (BBB) permeability to low dosage of ENR through comprehensively assessing expression of BBB constitutive molecules zonula occludens-1 (ZO-1) and permeability glycoprotein (P-gp), as well as ENR residue in brain of crucian carp. Toxicologic effect of ENR on brain tissue was determined through evaluating expression of brain-derived proteins S100B, neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP) in crucian carp brain tissue, as well as contents of the proteins in serum. The toxicological mechanisms were explored through analyzing transcriptome analysis data. Results showed that ENR possessed excellent permeability to crucian carp BBB, which was closely related to deranged BBB structure and declined ENR efflux that were attributed to downregulated expression of ZO-1 and P-gp by ENR exposure. Meanwhile, S100B, NSE and GFAP were upregulated in brain by ENR, and came out into blood across the damaged BBB. These data revealed that ENR induced disruption of BBB and damage of brain tissue in crucian carp. Transcriptome analysis data indicated that ENR induced toxicologic effect might be related to modification of metabolism, organismal systems, and genetic information processing, etc., and that PI3K/Akt, MAPK, HIF-1, and ubiquitin mediated proteolysis involved the mechanisms, most of the mechanisms were attributed to ENR induced oxidative stress in crucian carp brain.


Assuntos
Carpas , Carpa Dourada , Animais , Carpa Dourada/metabolismo , Enrofloxacina/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Carpas/metabolismo , Encéfalo/metabolismo
18.
Artigo em Inglês | MEDLINE | ID: mdl-37661043

RESUMO

Due to its water solubility and wide applicability, enrofloxacin hydrochloride (EH) may enter aquatic ecosystems and cause negative effects on aquatic organisms. This study aimed to explore toxicological effects via serological changes and neurotoxicity, which were induced by EH exposure in crucian carp (Carassius auratus var. Pengze). The drug residues in brain tissue and protein content in serum were determined to analyze serological changes. Alterations in brain tissue structure and function, cerebral microvessels permeability, and the expressions of gene and protein regarding blood-brain barrier (BBB) were studied to reflect the neurotoxicity. Employing a validated high-performance liquid chromatography (HPLC) method, EH residues could be detected at various time-points throughout the experiment. Enzyme-linked immunosorbent assay (ELISA) showed that EH increased the levels of S100B, NSE and GFAP proteins in serum. Additionally, there was a significant positive correlation between serum S100B, NSE protein contents and EH residues (P < 0.05). Hematoxylin and eosin (H&E) staining revealed brain damage from EH exposure by the formation of vacuoles in brain glial cells, pyknosis of the nucleus, and a decrease in cell population density. Transmission electron microscope (TEM) revealed morphological changes in microvessels and condensation of astrocyte nucleus. Evans blue (EB) permeability test visualized an obvious increase in cerebral microvessels leakage. The real-time quantitative PCR (qPCR) results indicated that EH up-regulated the mRNA expression levels of S100B, NSE and GFAP, down-regulated the mRNA expression levels of P-gp, ZO-1, Occludin and Claudin-5. The Western blot (WB) results demonstrated increased NSE and GFAP protein expressions, decreased P-gp and Occludin protein expressions following EH exposure in brain, in consistent with the gene expressions, respectively. In conclusion, these findings indicated that EH brought about marked rise in serum biomarker levels and disrupted the central nervous system (CNS) of crucian carp. These data would help elucidate the mechanism underlying EH-induced neurotoxicological effects.


Assuntos
Carpas , Síndromes Neurotóxicas , Animais , Enrofloxacina/toxicidade , Ecossistema , Ocludina , RNA Mensageiro
19.
Vet Med Sci ; 8(6): 2404-2410, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36037402

RESUMO

BACKGROUND: Enrofloxacin (ENR) is a kind of quinolone antibiotic that is most widely used antimicrobials in veterinary practice, and possesses both a broad spectrum antimicrobial activity against a range of bacteria and adverse effects towards plants and animals. OBJECTIVES: This study was conducted to explore the permeability of blood-brain barrier (BBB) to ENR and brain injury based on crucian carp orally administrated with high dose of ENR. METHODS: Juvenile Pengze crucian carp were treated with half lethal dose (LD50 ) or safe dose (SD50 ) of ENR. BBB permeability was determined by evaluating ENR contents detected by HPLC and evens blue contents estimated by confocal laser scanning microscope. Brain damage was evaluated by measuring protein and mRNA contents of related molecules with western blotting and qPCR. RESULTS: Data indicated that ENR destroyed BBB structure of crucian carp and enhanced permeability of the biological barrier, resulting in more ENR crossed BBB and induced brain damage of crucian carp. CONCLUSIONS: This data indicated that ENR can induce brain damage of crucian carp through destroying BBB structure and enhancing permeability.


Assuntos
Carpas , Carpa Dourada , Animais , Enrofloxacina , Barreira Hematoencefálica , Permeabilidade
20.
Carbohydr Polym ; 276: 118715, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34823761

RESUMO

Four fractions of water-extracted Sepia esculenta ink polysaccharides (SIP) were separated by dicthylaminoethy (DEAE) cellulose chromatography. The eluted fraction with the highest yield was characterized as a sulfate-rich glycosaminoglycan named SIP-IV. According to the analysis of laser scattering and refractive index signals, SIP-IV was determined to be 14.4 kDa and spherical molecular conformation in salt solution. SIP-IV is composed of fucose, galactosamine, glucosamine, mannose and glucuronic acid with a molar ratio of 5.1:7.3:3.8:1:4.4, which is obviously different from reported SIPs. SIP-IV promoted yeast proliferation and intercellular antioxidant level. Based on multi-omics strategy, data of transcriptome analysis suggested that growth promotion of SIP-IV on Saccharomyces cerevisiae might be attributed to regulation of Rho protein signal transduction, nuclear autophagy and nitrogen utilization. Combined with the metabolome results, SIP-IV also re-profiled metabolism of amino acids and phospholipids in yeast cells.


Assuntos
Glicosaminoglicanos/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos , Sepia/química , Sulfatos/química , Animais , Antioxidantes/metabolismo , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glicosaminoglicanos/química , Tinta , Metaboloma , Conformação Molecular , Peso Molecular , Saccharomyces cerevisiae/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transcriptoma
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