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1.
Artigo em Chinês | MEDLINE | ID: mdl-32062887

RESUMO

Objective: To investigate the antagonistic effect of diallyl sulfide (DAS) against peripheral nerve injury induced by n-hexane in rats. Methods: A total of 68 adult male Wistar rats were selected, among which 50 were randomly selected and divided into blank control group, DAS control group (100 mg/kg·bw) , n-hexane model group, low-dose DAS intervention group (50 mg/kg·bw) , and high-dose DAS intervention group (100 mg/kg·bw) . A rat model of peripheral nerve injury was established by n-hexane exposure, and the rats were treated with DAS at different doses. The changes in pyrrole adducts and behavior were observed, a metabolic analysis was performed for serum pyrrole adducts, and the intervention effect was evaluated. The remaining 18 rats were randomly assigned to the n-hexane model group, the low-dose DAS intervention group, and the high-dose DAS intervention group, with 6 rats in each group, as satellite groups used for the toxicokinetic analysis of serum pyrrole adducts. Results: Compared with the blank control group, the n-hexane model group and low-and high-dose DAS intervention groups had a significant reduction in body weight since week 2 (P<0.01) . Compared with the n-hexane model group at the end of the experiment at week 7, the high-dose DAS intervention group had a significantly higher body weight (P<0.05) , while there was no significant difference in body weight between the n-hexane model group and the low-dose DAS intervention group (P>0.05) . The n-hexane model group developed gait abnormality at week 2 of poisoning, while the low-and high-dose DAS intervention groups developed gait abnormality at weeks 3 and 5 of poisoning, respectively. At the end of the experiment, the n-hexane model group and the low-and high-dose DAS intervention groups had a significantly higher gait score than the blank control group (P<0.01) . At the end of the experiment, the n-hexane model group and the low-dose DAS intervention group had significantly shorter latency in rotarod test than the blank control group (P<0.01) , while there was no significant difference in latency between the DAS control group and the high-dose DAS intervention group (P>0.05) . Compared with the n-hexane model group, the low-and high-dose DAS intervention groups had a significant increase in latency in rotarod test (P<0.01) . Compared with blank control group, the n-hexane model group and the low-dose DAS intervention group had a significant increase in mean nerve conduction velocity (P<0.01) , while there was no significant difference between the blank control group and the DAS control group or high-dose DAS intervention group (P>0.05) , and compared with the n-hexane model group, the low-and high-dose DAS intervention groups had a significant increase in nerve conduction velocity (P<0.01) . Compared with the blank control group at the end of the experiment at week 7, the n-hexane model group and the low-and high-dose DAS intervention groups had significant increases in the concentration of pyrrole adducts in serum, urine, and hair (P<0.01) , while there was no significant difference between the blank control group and the DAS control group (P>0.05) , and the high-dose DAS intervention group had a significantly lower concentration of pyrrole adducts in serum, urine, and hair than the low-dose DAS intervention group (P<0.05) . Serum pyrrole adducts reached the peak level at 9-12 hours and then started to decrease. Compared with the n-hexane model group, the high-and low-dose DAS intervention groups had a significantly shorter half-life period of serum pyrrole adducts (P<0.01) . Compared with the n-hexane model group, the high-and low-dose DAS intervention groups had a significant reduction in the area under the curve of serum pyrrole adducts (P<0.05) . Conclusion: DAS can antagonize peripheral nerve injury induced by n-hexane.


Assuntos
Compostos Alílicos/farmacologia , Hexanos/toxicidade , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Sulfetos/farmacologia , Animais , Masculino , Traumatismos dos Nervos Periféricos/induzido quimicamente , Ratos , Ratos Wistar
2.
J Agric Food Chem ; 68(6): 1571-1578, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-31927886

RESUMO

Diallyl trisulfide (DATS) is a secondary metabolite of allicin, a volatile organosulfur flavoring compound generated by the crushing of garlic. These compounds have various medicinal effects such as antiplatelet activity. In this study, we demonstrated for the first time the cellular mechanism involved in the inhibition of platelet aggregation by DATS and dipropyl trisulfide (DPTS), which is a saturated analogue of DATS. Washed murine platelets were incubated with these sulfides, and platelet aggregation was evaluated by light transmission aggregometry. The amount of reaction products produced by DATS, DPTS, and glutathione (GSH) was measured using liquid chromatography-mass spectrometry. Compared with DPTS, DATS potently inhibited platelet aggregation induced by thrombin, U46619, and collagen. N-Ethylmaleimide (NEM), which is commonly used to modify sulfhydryl groups, also suppressed platelet aggregation. The reactivity of DATS with GSH was higher than that of DPTS. These data suggested that DATS inhibited platelet aggregation through the reaction of sulfhydryl groups.


Assuntos
Compostos Alílicos/química , Compostos Alílicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Compostos de Sulfidrila/farmacologia , Sulfetos/química , Sulfetos/farmacologia , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Dissulfetos/química , Dissulfetos/farmacologia , Alho/química , Glutationa/química , Camundongos , Agregação Plaquetária/efeitos dos fármacos , Compostos de Sulfidrila/química
3.
J Ethnopharmacol ; 247: 112299, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606537

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hua-Feng-Dan (HFD) is a traditional Chinese medicine used for neurological disorders. HFD contains cinnabar (HgS) and realgar (As4S4). The ethnopharmacological basis of cinnabar and realgar in HFD is not known. AIM OF THE STUDY: To address the role of cinnabar and realgar in HFD-produced neuroprotection against neurodegenerative diseases and disturbance of gut microbiota. MATERIALS AND METHODS: Lipopolysaccharide (LPS) plus rotenone (ROT)-elicited rat dopaminergic (DA) neuronal damage loss was performed as a Parkinson's disease animal model. Rats were given a single injection of LPS. Four months later, rats were challenged with the threshold dose of ROT. The clinical dose of HFD was administered via feed, starting from ROT administration for 46 days. Behavioral dysfunction was detected by rotarod and Y-maze tests. DA neuron loss and microglial activation were assessed via immunohistochemical staining and western bolt analysis. The colon content was collected to extract bacterial DNA followed by real-time PCR analysis with 16S rRNA primers. RESULTS: LPS plus ROT induced neurotoxicity, as evidenced by DA neuron loss in substantia nigra, impaired behavioral functions and increased microglial activation. HFD-original (containing 10% cinnabar and 10% realgar) rescued loss of DA neurons, improved behavioral dysfunction and attenuated microglial activation. Compared with HFD-original, HFD-reduced (3% cinnabar and 3% realgar) was also effective, but to be a less extent, while HFD-removed (without cinnabar and realgar) was ineffective. In analysis of gut microbiome, the increased Verrucomicrobiaceae and Lactobacteriaceae, and the decreased Enterobacteeriaceae by LPS plus ROT were ameliorated by HFD-original, and to be the less extent by HFD-reduced. CONCLUSION: Cinnabar and realgar are active ingredients in HFD to exert beneficial effects in a neurodegenerative model and gut microbiota.


Assuntos
Arsenicais/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Compostos de Mercúrio/farmacologia , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/tratamento farmacológico , Sulfetos/farmacologia , Animais , Arsenicais/química , Arsenicais/uso terapêutico , DNA Bacteriano/isolamento & purificação , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/patologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Enterobacteriaceae/isolamento & purificação , Etnofarmacologia , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Humanos , Mediadores da Inflamação/metabolismo , Lactobacillaceae/efeitos dos fármacos , Lactobacillaceae/genética , Lactobacillaceae/isolamento & purificação , Lipopolissacarídeos/toxicidade , Masculino , Compostos de Mercúrio/química , Compostos de Mercúrio/uso terapêutico , Microglia/efeitos dos fármacos , Microglia/imunologia , Microglia/patologia , Degeneração Neural , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/imunologia , Síndromes Neurotóxicas/patologia , RNA Ribossômico 16S/genética , Ratos , Rotenona/toxicidade , Sulfetos/química , Sulfetos/uso terapêutico , Verrucomicrobia/efeitos dos fármacos , Verrucomicrobia/genética , Verrucomicrobia/isolamento & purificação
4.
Artigo em Inglês | MEDLINE | ID: mdl-31669372

RESUMO

The razor clam Sinonovacula constricta is a commercial benthic bivalve, and burrows the deeper cave than the other buried benthic bivalves. Due to the little exchange of seawater and to anoxic conditions, S. constricta is exposed to considerable amounts of sulfide during low tide, but exhibits strong sulfide tolerance. Mitochondrial sulfide oxidation is a particular defense strategy against sulfide toxicity of sulfide-tolerant organisms, for which sulfide:quinone oxidoreductase (SQR) is the first key enzyme. In order to investigate the mechanism of sulfide tolerance in S. constricta, its SQR (designated as ScSQR), was cloned and characterized. The full-length cDNA of ScSQR was 3698 bp and encoded 443 amino acids. The deduced ScSQR protein contained conserved FAD-binding domains, two cysteine residues, two histidines, and one glutamic acid, which are the essential elements for the catalytic mechanism of SQR. Subcellular localization analysis by the TargetP 1.1 prediction and the Western blot confirmed that ScSQR was only located in the mitochondria. The response of ScSQR in the gill and liver of S. constricta were investigated during sulfide exposure (50, 150, and 300 µM sulfide) for 0, 3, 6, 12, 24, 48, 72, and 96 h by qRT-PCR. Moreover, the time-course expressions of ScSQR protein in the S. constricta gill were detected when exposed to 150 µM sulfide by Western blot. The expression level of ScSQR increased significantly and showed a time-dependent pattern. In addition, under sulfide stress, the expression level of the gill was higher than that of liver. Together, our results suggest that ScSQR may perform important roles in protecting cells from sulfide stress by participating in mitochondrial sulfide detoxification and providing high sulfide tolerance to S. constricta.


Assuntos
Bivalves/embriologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Quinona Redutases/biossíntese , Estresse Fisiológico/efeitos dos fármacos , Sulfetos/farmacologia , Animais , Brânquias/enzimologia , Fígado/enzimologia
5.
World J Microbiol Biotechnol ; 36(1): 4, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31832786

RESUMO

Colletotrichum gloeosporioides, one of the main agents of mango anthracnose, causes latent infections in unripe mango, and leads to huge economic losses during storage and transport. Dimethyl trisulfide (DMTS), one of the main volatile compounds produced by some microorganisms or plants, has shown antifungal activity against some phytopathogens in previous studies, but its effects on C. gloeosporioides and mechanisms of action have not been well characterized. In fumigation trials of conidia and mycelia of C. gloeosporioides for 2, 4, 6, 8, or 10 h, at a concentration of 100 µL/L of air space in vitro, DMTS caused serious damage to the integrity of plasma membranes, which significantly reduced the survival rate of spores, and resulted in abnormal hyphal morphology. Moreover, DMTS caused deterioration of subcellular structures of conidia and mycelia, such as cell walls, plasma membranes, Golgi bodies, and mitochondria, and contributed to leakage of protoplasm, thus promoting vacuole formation. In addition, to better understand the molecular mechanisms of the antifungal activity, the global gene expression profiles of isolate C. gloeosporioides TD3 treated in vitro with DMTS at a concentration of 100 µL/L of air for 0 h (Control), 1 h, or 3 h were investigated by RNA sequencing (RNA-seq), and over 62 Gb clean reads were generated from nine samples. Similar expressional patterns for nine differentially expressed genes (DEGs) in both RNA-seq and qRT-PCR assays showed the reliability of the RNA-seq data. In comparison to the non-treated control groups, we found DMTS suppressed expression of ß-1, 3-D-glucan, chitin, sterol biosynthesis-related genes, and membrane protein-related genes. These genes related to the formation of fungal cell walls and plasma membranes might be associated with the toxicity of DMTS against C. gloeosporioides. This is the first study demonstrating antifungal activity of DMTS against C. gloeosporioides on mango by direct damage of conidia and hyphae, thus providing a novel tool for postharvest control of mango anthracnose.


Assuntos
Antifúngicos/farmacologia , Colletotrichum/efeitos dos fármacos , Mangifera/microbiologia , Sulfetos/farmacologia , Quitina/metabolismo , Colletotrichum/isolamento & purificação , Contaminação de Alimentos , Microbiologia de Alimentos , Regulação Fúngica da Expressão Gênica , Hifas/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Viabilidade Microbiana , Microscopia Eletrônica de Transmissão , Micélio/efeitos dos fármacos , Doenças das Plantas/microbiologia , RNA Fúngico/genética , RNA Fúngico/isolamento & purificação , Reprodutibilidade dos Testes , Alinhamento de Sequência , Análise de Sequência de RNA , Esporos Fúngicos/efeitos dos fármacos , Esporos Fúngicos/isolamento & purificação , Esteróis/metabolismo , beta-Glucanas/metabolismo
6.
Int J Nanomedicine ; 14: 9577-9586, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824152

RESUMO

Purpose: Quantum dots (QDs) are widely used semiconductor nanomaterials. Indium phosphide/zinc sulfide (InP/ZnS) QDs are becoming potential alternatives to toxic heavy metal-containing QDs. However, the potential toxicity and, in particular, the immunotoxicity of InP/ZnS QDs are unknown. This study aimed to investigate the impacts of InP/ZnS QDs on inflammatory responses both in vivo and in vitro. Methods: Mice and mouse bone marrow-derived macrophages (BMMs) were exposed to polyethylene glycol (PEG) coated InP/ZnS QDs. The infiltration of neutrophils and the release of interleukin-6 (IL-6) were measured using a hematology analyzer and an enzyme-linked immunosorbent assay (ELISA) for the in vivo test. Cytotoxicity, IL-6 secretion, oxidative stress and endoplasmic reticulum (ER) stress were studied in the BMMs, and then, inhibitors of oxidative stress and ER stress were used to explore the mechanism of the InP/ZnS QDs. Results: We found that 20 mg/kg PEG-InP/ZnS QDs increased the number of neutrophils and the levels of IL-6 in both peritoneal lavage fluids and blood, which indicated acute phase inflammation in the mice. PEG-InP/ZnS QDs also activated the BMMs and increased the production of IL-6. In addition, PEG-InP/ZnS QDs triggered oxidative stress and the ER stress-related PERK-ATF4 pathway in the BMMs. Moreover, the inflammatory response caused by the PEG-InP/ZnS QDs could be attenuated in the macrophages by blocking the oxidative stress or the ER stress with inhibitors. Conclusion: InP/ZnS QDs can activate macrophages and induce acute phase inflammation both in vivo and in vitro, which may be regulated by oxidative stress and ER stress. Our present work is expected to help clarify the biosafety of InP/ZnS QDs and promote their safe application in biomedical and engineering fields.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Índio/farmacologia , Macrófagos/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosfinas/farmacologia , Pontos Quânticos/química , Sulfetos/farmacologia , Compostos de Zinco/farmacologia , Animais , Feminino , Depuradores de Radicais Livres/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/genética , Inflamação/patologia , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Pontos Quânticos/ultraestrutura , Espécies Reativas de Oxigênio/metabolismo
7.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 37(10): 737-745, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31726503

RESUMO

Objective: To investigate the antioxidant mechanism of diallyl sulfide (DAS) in antagonizing the reduction in peripheral blood white blood cells (WBC) induced by benzene in rats. Methods: A total of 60 specific pathogen-free adult male Sprague-Dawley rats, with a body weight of 180-220 g, were selected, and after 5 days of adaptive feeding, they were randomly divided into blank control group, DAS control group, benzene model group, benzene+low-dose DAS group, benzene+middle-dose DAS group, and benzene+high-dose DAS group, with 10 rats in each group. The rats in the benzene+low-dose DAS group, the benzene+middle-dose DAS group, the benzene+high-dose DAS group, and the DAS control group were given DAS by gavage at a dose of 40, 80, 160, and 160 mg/kg·bw, respectively, and those in the blank control group and the benzene model group were given an equal volume of corn oil; 2 hours later, the rats in the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group were given a mixture of benzene (1.3 g/kg·bw) and corn oil (with a volume fraction of 50%), and those in the blank control group and the DAS control group were given an equal volume of corn oil. The above treatment was given once a day for 4 consecutive weeks. At 1 day before treatment, anticoagulated blood was collected from the jugular vein for peripheral blood cell counting. After anesthesia with intraperitoneally injected pentobarbital (50 mg/kg·bw), blood samples were collected from the abdominal aorta, serum was isolated, and the thymus, the spleen, and the femur were freed at a low temperature to measure oxidative and antioxidant indices. The femur at one side was freed for WBC counting in bone marrow. Results: Compared with the blank control group, the benzene model group had significant reductions in the volume, weight, and organ coefficient of the spleen and the thymus (P<0.05) ; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had significant increases in the volume of the spleen and the thymus and the weight and organ coefficient of the spleen (P<0.05), and the benzene+middle-dose DAS group and the benzene+high-dose DAS group had significant increases in the weight and organ coefficient of the thymus (P<0.05). Compared with the blank control group, the benzene model group had a significant reduction in WBC count in peripheral blood and bone marrow (P<0.05), and compared with the benzene model group, the benzene+middle-dose DAS group and the benzene+high-dose DAS group had a significant increase in WBC count in peripheral blood and bone marrow (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the serum level of malondialdehyde (MDA) (P<0.05) and significant reductions in total superoxide dismutase (T-SOD) activity, reduced glutathione (GSH) level, GSH/oxidized glutathione (GSSG) ratio, total antioxidant capacity (T-AOC) (P<0.05) ; compared with the benzene model group, the benzene+high-dose DAS group had a significant reduction in the serum level of MDA and significant increases in T-SOD activity, GSH level, GSH/GSSG ratio, and T-AOC (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the level of MDA (P<0.05) and significant reductions in GSH level, GSH/GSSG ratio, and T-AOC (P<0.05) in the spleen; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had a significant reduction in MDA level (P<0.05) and significant increases in GSH level and T-AOC (P<0.05), and the benzene+high-dose DAS group had significant increases in T-SOD activity and GSH/GSSG ratio (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the level of MDA in bone marrow cells (BMCs) and peripheral blood mononucleated cells (PBMCs) (P<0.05) and a significant reduction in T-AOC in PBMCs (P<0.05) ; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had a significant reduction in the level of MDA in BMCs and PBMCs (P<0.05), and the benzene+high-dose DAS group had significant increases in GSH level and GSH/GSSG ratio (P<0.05) . Conclusion: DAS can antagonize the benzene-induced reduction in peripheral blood WBC, possibly by exerting an anti-oxidative stress effect.


Assuntos
Compostos Alílicos/farmacologia , Antioxidantes/farmacologia , Leucopenia/tratamento farmacológico , Sulfetos/farmacologia , Animais , Benzeno/efeitos adversos , Glutationa/análise , Leucopenia/induzido quimicamente , Masculino , Malondialdeído/análise , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/análise
8.
J Agric Food Chem ; 67(46): 12696-12708, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31657554

RESUMO

In this study, a type of thiazolium-labeled 1,3,4-oxadiazole thioether bridged by diverse alkyl chain lengths was constructed. The antimicrobial activity of the fabricated thioether toward plant pathogenic bacteria and fungi was then screened. Antibacterial evaluation indicated that title compounds possess specific characteristics that enable them to severely attack three phytopathogens, namely, Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri with minimal EC50 values of 0.10, 3.27, and 3.50 µg/mL, respectively. Three-dimensional quantitative structure-activity relationship models were established to direct the following excogitation for exploring higher active drugs. The in vivo study against plant bacterial diseases further identified the prospective application of title compounds as alternative antibacterial agents. The proteomic technique, scanning electron microscopy patterns, and fluorescence spectrometry were exploited to investigate the antibacterial mechanism. Additionally, some target compounds performed superior inhibitory actions against three tested fungal strains. In view of their simple molecular architecture and highly efficient bioactivity, these substrates could be further explored as promising surrogates for fighting against plant microbial infections.


Assuntos
Antibacterianos/farmacologia , Oxidiazóis/farmacologia , Sulfetos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Testes de Sensibilidade Microbiana , Oxidiazóis/síntese química , Oxidiazóis/química , Doenças das Plantas/microbiologia , Ralstonia/efeitos dos fármacos , Sulfetos/síntese química , Sulfetos/química , Xanthomonas/efeitos dos fármacos
10.
Chem Commun (Camb) ; 55(87): 13128-13131, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31616871

RESUMO

We report here a novel light-triggered nanosystem based on co-assembling nanoaggregates (NAs) of lipophilic photosensitizers and lipophilic prodrugs containing multiple thioethers. Upon laser irradiation, the oxidization of the multiple thioethers by photosensitizer-generated singlet oxygen could rapidly destroy the NA structure, resulting in faster drug release than those containing a single thioether.


Assuntos
Luz , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Pró-Fármacos/química , Sulfetos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Humanos , Estrutura Molecular , Tamanho da Partícula , Fármacos Fotossensibilizantes/farmacologia , Pró-Fármacos/farmacologia , Oxigênio Singlete/química , Sulfetos/farmacologia , Propriedades de Superfície
11.
Eur J Med Chem ; 184: 111745, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31585237

RESUMO

Hydrogen sulphide (H2S) is an endogenous gasotransmitter, largely known as a pleiotropic mediator endowed with antioxidant, anti-inflammatory, pro-autophagic, and neuroprotective properties. Moreover, a strong relationship between H2S and aging has been recently identified and consistently, a significant decline of H2S levels has been observed in patients affected by Alzheimer's disease (AD). On this basis, the use of H2S-donors could represent an exciting and intriguing strategy to be pursued for the treatment of neurodegenerative diseases (NDDs). In this work, we designed a small series of multitarget molecules combining the rivastigmine-scaffold, a well-established drug already approved for AD, with sulforaphane (SFN) and erucin (ERN), two natural products deriving from the enzymatic hydrolysis of glucosinolates contained in broccoli and rocket, respectively, endowed both with antioxidant and neuroprotective effects. Notably, all new synthetized hybrids exhibit a H2S-donor profile in vitro and elicit protective effects in a model of LPS-induced microglia inflammation. Moreover, a decrease in NO production has been observed in LPS-stimulated cells pre-treated with the compounds. Finally, the compounds showed neuroprotective and antioxidant activities in human neuronal cells. The most interesting compounds have been further investigated to elucidate the possible mechanism of action.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antioxidantes/farmacologia , Sulfeto de Hidrogênio/farmacologia , Isotiocianatos/farmacologia , Fármacos Neuroprotetores/farmacologia , Rivastigmina/farmacologia , Animais , Antioxidantes/síntese química , Antioxidantes/química , Linhagem Celular , Relação Dose-Resposta a Droga , Desenho de Drogas , Humanos , Sulfeto de Hidrogênio/síntese química , Sulfeto de Hidrogênio/química , Isotiocianatos/síntese química , Isotiocianatos/química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Rivastigmina/síntese química , Rivastigmina/química , Relação Estrutura-Atividade , Sulfetos/síntese química , Sulfetos/química , Sulfetos/farmacologia , Tiocianatos/síntese química , Tiocianatos/química , Tiocianatos/farmacologia
12.
Ecotoxicol Environ Saf ; 185: 109679, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31550564

RESUMO

Sodium sulfide (Na2S) was used as an inducer to regulate the components of Bacillus vallismortis sp. EPS (Extracellular Polymeric Substances). The main objective of this study was to improve the content of sulfhydryl protein and the adsorption property of EPS to Zn (Ⅱ) that as an typical heavy metal. The results showed that the maximum EPS production of 105.58 mg/g VSS coupling with doubled increase in protein in which the contant of -SH increased by 48.2% from 104.15 to 154.36 µmol/L were recorded in the presence of 20 mg/L Na2S. Under this condition, the adsorption capacity of S-EPS (EPS with added exogenous Na2S) for Zn (Ⅱ) was highest. The kinetics of the adsorption process of Zn (Ⅱ) by the S-EPS can be well fitted by the Langmuir isotherm model and the theoretical maximum adsorption amount of 979.09 mg/g EPS could be obtained. The results of 3D-EEM and FTIR analyses, illustrated that -SH, CO, and N-H/C-N played major roles in the removal of Zn (Ⅱ) by S-EPS. The results obtained in this study demonstrated that the addition of sulfur source could increase the content of sulfhydryl protein, and effectively regulate the content of chemical composition, expecially for the sulfhydryl of EPS, and thereby greatly improving the removal efficiency of heavy metals, which showed a great application prospect in the prevention and control of heavy metal pollution.


Assuntos
Bacillus/metabolismo , Poluentes Ambientais/metabolismo , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Metais Pesados/metabolismo , Sulfetos/farmacologia , Adsorção , Cinética
13.
Artif Cells Nanomed Biotechnol ; 47(1): 3832-3838, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31556316

RESUMO

High atomic number Z, nanoparticles are able to enhance the photoelectric and Compton effects under X-Ray irradiation resulting the increase of radiation therapy efficacy. To achieve enhanced radiation therapy, Bi2S3 biocompatible particles coated with bovine serum albumin (BSA) (Bi2S3@BSA HNPs) were prepared through a BSA-mediated biomineralization procedure under green conditions. Then, to achieve improved chemo-radiation therapy against HT-29 cancer cells, curcumin (CUR) as natural anti-cancer therapy agent loaded on the Bi2S3@BSA (Bi2S3@BSA@CUR HNPs). Next, this synthesized nanodrug was evaluated for physical and chemical properties and in vitro cytotoxicity studies. Here, in vitro enhanced chemo-radiation combination therapy power was evaluated against HT-29 cell line under 2 Gy and 6 Gy X-ray irradiation doses. The Bi2S3@BSA HNPs without irradiation rarely affect cell viability which shown the non-toxicity of Bi2S3@BSA HNPs. The result of this study proved that Bi2S3@BSA@CUR HNPs can be used as both proficient vehicles for effective delivery of CUR and radiosensitizer in the treatment of cancer. In addition, the result of this study confirmed that the combination of high Z-element nanoradiosensitizer, Bi2S3@BSA HNPs, with a natural anti-cancer drug, CUR, enhanced therapeutic power against HT-29 cells.


Assuntos
Bismuto/farmacologia , Quimiorradioterapia , Minerais/química , Soroalbumina Bovina/química , Sulfetos/síntese química , Sulfetos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Bismuto/química , Bovinos , Técnicas de Química Sintética , Materiais Revestidos Biocompatíveis/síntese química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Curcumina/química , Curcumina/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Liberação Controlada de Fármacos , Química Verde , Células HT29 , Humanos , Nanopartículas/química , Tamanho da Partícula , Radiossensibilizantes/síntese química , Radiossensibilizantes/química , Radiossensibilizantes/farmacologia , Sulfetos/química
14.
ACS Appl Mater Interfaces ; 11(41): 37411-37420, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31556583

RESUMO

Liposomes are the most valuable nanocarriers in clinical use because of their biocompatibility, biodegradation, and effective encapsulation of hydrophilic or hydrophobic drugs. However, their applications are limited by the structure and functions of the most common phospholipids used as the main component of the liposomes. In this work, novel series of thioether phosphatidylcholines (S-PCs) and S-PC-based liposomes (S-LPs) were developed for reactive oxygen species (ROS)-responsive drug release. First of all, S-PCs with different chain lengths were synthesized by a combination of click reaction and heterogeneous esterification. Differential scanning calorimetry studies indicated that S-PCs had different phase transition temperatures depending on their chain lengths. Their critical aggregation concentrations were measured by the fluorescence probe technique indicating the self-assembly ability. After that, S-PC-based stealth liposomes (S-LPs) containing DSPE-PEG2000 and cholesterol were prepared via a classic thin-film method. Doxorubicin (DOX) as a model drug was loaded in the stealth liposomes (DOX/S-LPs) by using the ammonium sulfate gradient method with high encapsulation efficiency. DOX/S-LPs were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), and cryogenic TEM, confirming their spherical structure with the bilayer thickness of about 4 nm. The ROS sensitivity of S-PCs and S-LPs was carefully evaluated in the presence of H2O2 by means of mass spectrometry, DLS, TEM, and ultraviolet spectroscopy and release study. The results indicated the significant structural change of S-LPs after H2O2 treatment, which demonstrated that S-LPs possessed an efficient ROS-triggered disintegration because of thioether oxidation of S-PCs. Finally, in vitro and in vivo anticancer efficiency assays revealed the improved drug potency of DOX/S-LPs, which can be attributed to ROS-triggered destruction of S-LPs after the uptake by tumor cells followed by rapid release of DOX. All together, as alternatives of traditional phosphatidylcholines, S-PC-based stealth liposomes are promising ROS-responsive carriers for the controlled delivery of drugs.


Assuntos
Doxiciclina , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Fosfatidilcolinas , Espécies Reativas de Oxigênio/metabolismo , Sulfetos , Células A549 , Animais , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Doxiciclina/química , Doxiciclina/farmacologia , Feminino , Humanos , Lipossomos , Células MCF-7 , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilcolinas/química , Fosfatidilcolinas/farmacologia , Sulfetos/química , Sulfetos/farmacologia
15.
J Agric Food Chem ; 67(42): 11598-11606, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31560195

RESUMO

A total of 22 quinazoline thioether derivatives incorporating a 1,2,4-triazolo[4,3-a]pyridine moiety were designed, synthesized, and evaluated as antimicrobial agents in agriculture. Among these compounds, the chemical structure of compound 6l was further confirmed via single-crystal X-ray diffraction analysis. The bioassay results revealed that some of the compounds possessed noticeable in vitro antibacterial activities against the tested phytopathogenic bacteria. For example, compounds 6b and 6g had EC50 values as low as 10.0 and 24.7 µg/mL against Xanthomonas axonopodis pv. citri (Xac), respectively, which were significantly better than that of the commercial agrobactericide bismerthiazol (56.9 µg/mL). Particularly, compound 6b was also found to be capable of suppressing the pathogenic bacterium Xanthomonas oryzae pv. oryzae (Xoo) approximately 12-fold more potent than control bismerthiazol, in terms of their EC50 values (7.2 versus 89.8 µg/mL). Importantly, the most active compound 6b turned out to be one with the highest hydrophilicity and the lowest molecular weight within the series. In vivo bioassays further showed the application prospect of 6b as a promising plant bactericide for controlling Xoo. Additionally, in vitro antifungal activities of these compounds were also evaluated at the concentration of 50 µg/mL. Overall, the present study demonstrated the potential of 1,2,4-triazolo[4,3-a]pyridine-bearing quinazoline thioether derivatives as efficient agricultural antibacterial agents for crop protection.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Quinazolinas/química , Quinazolinas/farmacologia , Sulfetos/química , Sulfetos/farmacologia , Agroquímicos/química , Agroquímicos/farmacologia , Antibacterianos/síntese química , Desenho de Drogas , Piridinas/química , Relação Estrutura-Atividade , Xanthomonas/efeitos dos fármacos
16.
Mater Sci Eng C Mater Biol Appl ; 104: 109954, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500027

RESUMO

Therapeutic angiogenesis is essential for rescuing necrotic tissues in cases of ischemic disease. The exogenous hydrogen sulfide (H2S) donor, diallyl trisulfide (DATS), has been investigated as a therapeutic agent that promotes angiogenesis. However, the short half-life of generated H2S limits its therapeutic efficacy. In an attempt to overcome this difficulty, a poly(D,L-lactic-co-glycolic acid) microparticle system that contains DATS (DATS@MPs) is prepared as an in situ depot for the controlled release of H2S, providing slow release and long-term effectiveness. The results of in vitro investigations indicate that the slow-released DATS from the DATS@MPs depot yields a longer intracellular production of H2S than that from a free DATS depot. The intracellular generation of H2S favors the translocation of the transcription factor, Nrf2, from the cytosol to nuclei, potentially upregulating the gene expressions of antioxidant enzymes, ultimately increasing cellular resistance to oxidative stress. Intramuscular injection of the slow-releasing H2S donor depot DATS@MPs in an ischemic limb that is experimentally generated in a mouse model promotes therapeutic angiogenesis and protects cells from apoptosis and tissues from necrosis, ultimately salvaging the limb. These analytical results reveal that DATS@MPs is potentially useful in H2S-based therapy for treating ischemic diseases.


Assuntos
Preparações de Ação Retardada/farmacologia , Sulfeto de Hidrogênio/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Compostos Alílicos/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Linhagem Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Sulfetos/farmacologia
17.
ACS Appl Mater Interfaces ; 11(35): 31735-31742, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31393101

RESUMO

Chemodynamic therapy based on Fe2+-catalyzed Fenton reaction holds great promise in cancer treatment. However, low-produced hydroxyl radicals in tumor cells constitute its severe challenges because of the fact that Fe2+ with high catalytic activity could be easily oxidized into Fe3+ with low catalytic activity, greatly lowering Fenton reaction efficacy. Here, we codeliver CuS with the iron-containing prodrug into tumor cells. In tumor cells, the overproduced esterase could cleave the phenolic ester bond in the prodrug to release Fe2+, activating Fenton reaction to produce the hydroxyl radical. Meanwhile, CuS could act as a nanocatalyst for continuously catalyzing the regeneration of high-active Fe2+ from low-active Fe3+ to produce enough hydroxyl radicals to efficiently kill tumor cells as well as a photothermal therapy agent for generating hyperthermia for thermal ablation of tumor cells upon NIR irradiation. The results have exhibited that the approach of photothermal therapy nanomaterials boosting transformation of Fe3+ into Fe2+ in tumor cells can highly improve Fenton reaction for efficient chemodynamic therapy. This strategy was demonstrated to have an excellent antitumor activity both in vitro and in vivo, which provides an innovative perspective to Fenton reaction-based chemodynamic therapy.


Assuntos
Compostos Férricos , Hipertermia Induzida , Neoplasias Experimentais , Fototerapia , Animais , Cobre/química , Cobre/farmacocinética , Cobre/farmacologia , Compostos Férricos/química , Compostos Férricos/farmacocinética , Compostos Férricos/farmacologia , Células HeLa , Humanos , Radical Hidroxila/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Sulfetos/química , Sulfetos/farmacocinética , Sulfetos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Chemosphere ; 237: 124359, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31394455

RESUMO

The effect of zinc oxide nanoparticles (ZnO NPs) and zinc sulfide nanoparticles (ZnS NPs) on the toxicity of sewage sludges in sewage sludge-amended soils was investigated with respect to plant- (Lepidium sativum) and soil- (Folsomia candida) species. The toxicity of porewater obtained from the tested soils towards Vibrio fischeri (Microtox®) was also investigated. Two sewage sludges (SSL1 and SSL2) with different organic matter content were amended with nanoparticles. Depending on the type of biotest and the type of sewage sludge, different effects of ZnO or ZnS NPs on the toxicity of sewage sludge-amended soil were observed. In general, ZnO and ZnS NPs stimulated root growth for SSL1 or reduced the harmful impact of SSL2 on the root growth of L. sativum roots. Greater stimulation or inhibition of root growth was observed for the ZnO than ZnS NPs. The unfavorable effect of ZnO/ZnS NPs on F. candida mortality and reproduction was observed at a concentration of ZnO/ZnS in sewage sludge ≥250 mg/kg. Generally, there were no significant differences between ZnO and ZnS NPs toxicity towards F. candida. Aging for 45 days of sewage sludge-amended soil containing NPs affected ZnO and ZnS NPs toxicity to all tested organisms. In the most cases, the toxicity decreased after 45 days of aging for plant (L. sativum) and invertebrates (F. candida). The toxicity of porewater to V. fischeri from sewage sludge-amended soil contains ZnO NPs did not change, while in the case of ZnS NPs, the toxicity increased after 45 days of aging.


Assuntos
Bactérias/efeitos dos fármacos , Invertebrados/efeitos dos fármacos , Nanopartículas/química , Plantas/efeitos dos fármacos , Solo/química , Aliivibrio fischeri/efeitos dos fármacos , Animais , Artrópodes/efeitos dos fármacos , Lepidium sativum/efeitos dos fármacos , Esgotos , Poluentes do Solo/análise , Sulfetos/farmacologia , Compostos de Zinco/farmacologia , Óxido de Zinco/farmacologia
19.
Int J Nanomedicine ; 14: 5581-5594, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413564

RESUMO

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder due to the existence of BCR-ABL fusion protein that allows the cells to keep proliferating uncontrollably. Although tyrosine kinase inhibitors can inhibit the activity of BCR-ABL fusion protein to trigger the cells apoptosis, drug resistance or intolerance exists in part of CML patients. Arsenic sulfide in its raw form (r-As4S4) can be orally administrated and certain therapeutic effects have been found out in the treatment of hematologic malignancies through inducing cell apoptosis. Methods: In this work, a water-dissolvable arsenic sulfide nanoformualtion (ee-As4S4) composed of As4S4 particulates with 470 nm in diameter and encapsulated by a kind of hydrophilic polymer was fabricated and applied to the CML cell line K562, K562/AO2 and primary cells from the bone marrow of CML patients. Results: Results showed that instead of inhibiting the activity of BCR-ABL, ee-As4S4 induced direct degradation of BCR-ABL in K562 cells within 6 hr incubation, followed by the occurrence of erythroid differentiation in K562 after 72 hr incubation, evidenced by the significantly upregulated CD235a and benzidine staining, which was not detectable with r-As4S4. The ee-As4S4-induced erythroid differentiation was also observed in K562/AO2 cells and bone marrow mononuclear cells of CML patients. Mechanistic studies indicated that ee-As4S4 induced autophagy by downregulating the level of intracellular ROS and hypoxia-inducible factor-1α significantly, which led to the subsequent degradation of BCR-ABL. When the concentration was increased, ee-As4S4 induced much more significant apoptosis and cell cycle arrest than r-As4S4, and the cytotoxicity of the former was about 178 times of the latter. Conclusion: ee-As4S4 was capable of inducing significant erythroid differentiation of CML cells by inducing the direct degradation of BCR-ABL; the new effect could improve hematopoietic function of CML patients as well as inhibit the leukemic cell proliferation.


Assuntos
Arsenicais/farmacologia , Diferenciação Celular/efeitos dos fármacos , Composição de Medicamentos , Células Eritroides/citologia , Proteínas de Fusão bcr-abl/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Nanopartículas/química , Proteólise/efeitos dos fármacos , Sulfetos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Células Eritroides/efeitos dos fármacos , Células Eritroides/ultraestrutura , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Toxicol Mech Methods ; 29(9): 702-709, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31364917

RESUMO

Leukopenia is the early clinical manifestation of benzene poisoning. The aim of our research was to evaluate the preventive effects of three kinds of garlic preparations on benzene induced leukopenia. The mouse model of Leukopenia was established with benzene orally. At the same time, mice were administrated with garlic homogenate (GH), garlic oil (GO) or diallyl trisulfide (DATS) as preventional measures. The counts of white blood cells (WBC), the organ indexes, pathological examinations, blood biochemical parameters, weight gains, and food intakes were evaluated to observe the protective effect and potential adverse events. The results demonstrated that the counts of WBC increased by 144.04%, 140.07%, and 148.34%, respectively, after intervention by GH (400 mg/kg), GO (60 mg/kg) and DATS (30 mg/kg), compared with that in the model group. The spleen and thymus indexes in the benzene model group were 44.99% and 54.04% lower than those in the blank control group, the number of spleen nodules reduced and the thymus atrophy, which were restored by three garlic preparations at different degree. The results suggested that the three preparations all could prevent the leukopenia and protect the organ injuries induced by benzene. However, the spleen index and weight gains revealed that GH and GO brought more adverse events than DATS.


Assuntos
Compostos Alílicos/farmacologia , Benzeno/toxicidade , Alho/química , Leucopenia/prevenção & controle , Preparações de Plantas/farmacologia , Sulfetos/farmacologia , Compostos Alílicos/efeitos adversos , Animais , Modelos Animais de Doenças , Contagem de Leucócitos , Leucopenia/sangue , Leucopenia/induzido quimicamente , Masculino , Camundongos Endogâmicos , Preparações de Plantas/efeitos adversos , Baço/efeitos dos fármacos , Baço/patologia , Sulfetos/efeitos adversos , Timo/efeitos dos fármacos , Timo/patologia
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