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1.
Rev Bras Parasitol Vet ; 30(1): e015920, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33605386

RESUMO

The consumption of inadequately thermally treated fish is a public health risk due to the possible propagation of Anisakis larvae. The present study demonstrated the physiological and histopathological changes that accompanied an oral inoculation of crude extracts from fresh and thermally treated Anisakis Type II (L3) in rats. Worms were isolated from a marine fish and examined and identified using light and scanning electron microscopy. The study was performed in 6 rat groups: control (I), garlic oil (GO) inoculated (II), fresh L3 inoculated (III), thermally treated L3 inoculated (IV), fresh L3 + GO inoculated (V), and a thermally treated L3 + GO inoculated (VI) groups. Rats inoculated with fresh and thermally treated L3 showed abnormal liver and kidney functions associated with the destruction of normal architecture. GO produced a protective effect in rat groups inoculated with L3 extracts + GO via the amelioration of liver and kidney functions, which was confirmed by the marked normal structure on histology. Cooking of L3-infected fish induced severe alterations compared to uncooked fish. The administration of garlic before and after fish eating is recommended to avoid the dangerous effect of anisakids, even if they are cooked.


Assuntos
Compostos Alílicos , Anisaquíase , Anisakis , Sulfetos , Compostos Alílicos/farmacologia , Compostos Alílicos/uso terapêutico , Animais , Anisaquíase/tratamento farmacológico , Anisaquíase/prevenção & controle , Anisakis/efeitos dos fármacos , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Culinária , Peixes/parasitologia , Parasitologia de Alimentos , Larva , Ratos , Ratos Wistar , Sulfetos/farmacologia , Sulfetos/uso terapêutico
2.
Medicine (Baltimore) ; 100(3): e23958, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545976

RESUMO

BACKGROUND: Pediatric obstructive sleep apnea syndrome (OSAS) is significant public concern. Clinical practice indicates that montelukast has certain therapeutic advantages, while there is a lack of evidence-based medicine support. The aim of this study is to synthesize related data to explore efficacy and safety of montelukast for pediatric OSAS. METHODS: Data in Pubmed, EMBASE, CENTRAL, CBM, CNKI, WanFang, VIP databases were comprehensively searched. All the randomized controlled trials (RCTs) in OSAS children were identified, in which the effects of montelukast on a range of outcomes were compared. The search had a deadline of January 1, 2020. Two investigators independently conducted data extraction and assessed the literature quality of the included studies. The Revman5.3 software was used for meta-analysis of the included literature. RESULTS: The efficacy and safety of montelukast in the treatment of pediatric OSAS were evaluated in terms of apnea hypopnea index (AHI), the Pittsburgh Sleep Quality Index, the Epworth Sleep Scale (ESS), neck circumference, important index in Polysomnography: sleep efficiency, desaturation index, total sleep time. CONCLUSIONS: This study provides reliable evidence-based support for the clinical application of montelukast in the treatment of pediatric OSAS. PROSPERO REGISTRATION NUMBER: CRD42020146940.


Assuntos
Acetatos/uso terapêutico , Protocolos Clínicos , Ciclopropanos/uso terapêutico , Quinolinas/uso terapêutico , Apneia Obstrutiva do Sono/tratamento farmacológico , Sulfetos/uso terapêutico , Acetatos/efeitos adversos , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Criança , Ciclopropanos/efeitos adversos , Humanos , Metanálise como Assunto , Polissonografia/métodos , Quinolinas/efeitos adversos , Apneia Obstrutiva do Sono/fisiopatologia , Sulfetos/efeitos adversos , Revisões Sistemáticas como Assunto
3.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(3): 235-239, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32981278

RESUMO

Objective: To investigate the effects of exogenous NaHS on myelin basic protein (MBP) and learning and memory of hippocampal neurons in mice with spinocerebellar ataxia type 3 (SCA3) and its therapeutic significance.Methods: Twelve male normal mice were randomly selected as normal control group (NC Group), and 48 SCA3 mice were randomly selected as SCA3 model group (M Group), low dose group (NL Group, 10 µmol/kg), medium dose group (NM Group, 50µmol/kg) and high dose group (NH Group, 100 µmol/kg), 12 rats in each group. The drug treated groups were injected with NaHS intraperitoneally once a day for 4 weeks. The changes of learning and memory ability of SCA3 mice before and after the intervention of different doses of NaHS were determined by Morris water maze, the content of hydrogen sulfide (H2S) in hippocampus was measured by spectrophotometry, the expression of MBP was detected by immunohistochemistry, and the morphological changes of neuron myelin sheath were observed by electron microscope. Results: Compared with the control group, the learning and memory ability of SCA3 mice was decreased significantly (P<0.05), and the content of H2S in hippocampus was decreased (P<0.05). After different doses of exogenous NaHS treatment, the learning and memory ability was improved in different degrees (P<0.05), and the contents of H2S and MBP in hippocampus of SCA3 mice were also improved in different degrees (P<0.05). Conclusion: Exogenous NaHS may increase the contents of H2S and MBP in the hippocampus of SCA3 mice, which may have a protective effect on the neurons, and then improve the learning and memory ability of SCA3 mice, and provide a new idea for the treatment of SCA3.


Assuntos
Sulfeto de Hidrogênio , Aprendizagem , Memória , Ataxias Espinocerebelares , Sulfetos , Animais , Hipocampo/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Camundongos , Proteína Básica da Mielina , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ataxias Espinocerebelares/tratamento farmacológico , Sulfetos/farmacologia , Sulfetos/uso terapêutico
4.
Ulus Travma Acil Cerrahi Derg ; 26(4): 503-508, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32589234

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is an important health problem. The most important hypotheses for the pathogenesis of this disease are the deterioration of immune responses and loss of tolerance against bacteria in the enteric flora. Although IBD has been widely investigated, its treatment remains difficult. This study aims to investigate the effects of garlic oil (GO) on an experimental colitis model. METHODS: Twenty-eight rats were randomly divided into four equal groups as follows: group 1 (sham), group 2 (control), group 3 (topical treatment) and group 4 (topical and systemic treatment). An acetic acid-induced colitis model was produced in groups 2, 3 and 4 and was administered normal saline, topical GO and topical and systemic GO, respectively. RESULTS: Hydroxyproline levels were lower in the treatment groups than in the control group. TNF-α levels were significantly lower in group 3 than in group 2. Macroscopic scores were significantly lower in group 4 than in group 2. Significant differences were observed between the treatment and control groups according to their epithelial loss. CONCLUSION: GO can reduce colonic damage and inflammation in the acetic acid-induced colitis model, with effects on both local and systemic treatments, but with a more pronounced effect in local treatment.


Assuntos
Ácido Acético/efeitos adversos , Compostos Alílicos/uso terapêutico , Colite/tratamento farmacológico , Sulfetos/uso terapêutico , Animais , Colite/induzido quimicamente , Modelos Animais de Doenças , Alho , Ratos
5.
Inorg Chem ; 59(8): 5662-5673, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32255617

RESUMO

A family of stable anticancer gold(III)-based therapeutic complexes containing cyclometalated triphenylphosphine sulfide ligands have been prepared. The anticancer properties of the newly developed complexes [AuCl2{κ2-2-C6H4P(S)Ph2}] (1), [Au(κ2-S2CNEt2){κ2-2-C6H4P(S)Ph2}]PF6 (2), [AuCl(dppe){κC-2-C6H4P(S)Ph2}]Cl (3), and [Au(dppe){κ2-2-C6H4P(S)Ph2}][PF6]2 (4) were investigated toward five human cancer cell lines [cervical (HeLa), lung (A549), prostate (PC3), fibrosarcoma (HT1080), and breast (MDA-MB-231)]. In vitro cytotoxicity studies revealed that compounds 2-4 displayed potent cell growth inhibition (IC50 values in the range of 0.17-2.50 µM), comparable to, or better than, clinically used cisplatin (0.63-6.35 µM). Preliminary mechanistic studies using HeLa cells indicate that the cytotoxic effects of the compounds involve apoptosis induction through ROS accumulation. Compound 2 also demonstrated significant inhibition of endothelial cell migration and tube formation in the angiogenesis process. Evaluation of the in vivo antitumor activity of compound 2 in nude mice bearing cervical cancer cell (HeLa) xenografts indicated significant tumor growth inhibition (55%) with 1 mg/kg dose (every 3 days) compared with the same dose of cisplatin (28%). These results demonstrate the potential of gold(III) complexes containing cyclometalated triphenylphosphine sulfide ligands as novel metal-based anticancer agents.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Complexos de Coordenação/uso terapêutico , Neoplasias/tratamento farmacológico , Fosfinas/uso terapêutico , Sulfetos/uso terapêutico , Inibidores da Angiogênese/síntese química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/uso terapêutico , Feminino , Ouro/química , Humanos , Ligantes , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfinas/síntese química , Espécies Reativas de Oxigênio/metabolismo , Sulfetos/síntese química , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
6.
J Vet Emerg Crit Care (San Antonio) ; 30(3): 302-307, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32077228

RESUMO

OBJECTIVE: To describe a case series of systemic lime sulfur toxicosis secondary to topical administration in 2 cats. CASE SUMMARY: Two cats from the same household that were being previously treated for Microsporum canis were presented following topical administration of an incorrectly diluted lime sulfur dip. A 30% solution was used rather than the recommended 3% solution, resulting in a 10-fold concentration overdose. The cats presented to the emergency service 1 hour after dermal application of the lime sulfur product at home. The first cat, a 2-year-old female, intact Cornish Rex, had severe hypotension, bradycardia, and hypothermia. Chemical burns were also present on the ventrum and paws. Clinicopathological data revealed profound acid-base disturbances, hypercalcemia, hyperphosphatemia, and azotemia. After aggressive fluid resuscitation, electrolyte supplementation, and treatment, the patient was stabilized and discharged after 5 days of hospitalization; full recovery was later reported. The second littermate, also a 2-year-old female, intact Cornish Rex, presented the following day with similar clinical signs, physical examination findings, and clinicopathological findings. After supportive care and 2 days of hospitalization, the patient was also discharged and reported to fully recover. NEW OR UNIQUE INFORMATION PROVIDED: This case series is the first to report systemic toxicosis secondary to dermal exposure of lime sulfur. As lime sulfur is commonly used in veterinary medicine for the treatment of ectoparasites, veterinary professionals should be aware of the significant signs of poisoning that can be seen as a result of iatrogenic dosing errors by pet owners or veterinary professionals.


Assuntos
Antifúngicos/efeitos adversos , Compostos de Cálcio/efeitos adversos , Doenças do Gato/induzido quimicamente , Sulfetos/efeitos adversos , Administração Tópica , Animais , Anti-Infecciosos , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Compostos de Cálcio/administração & dosagem , Compostos de Cálcio/uso terapêutico , Doenças do Gato/tratamento farmacológico , Gatos , Feminino , Microsporum , Sulfetos/administração & dosagem , Sulfetos/uso terapêutico
7.
Phytother Res ; 34(5): 1154-1165, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31984539

RESUMO

Diallyl trisulfide (DATS), derived from garlic, is a well-known hydrogen sulfide (H2 S) donor. H2 S has recently emerged as a novel gasotransmitter involved in the regulation of cancer progression. The present study demonstrated that DATS along with other two H2 S donors, NaHS and GYY4137, significantly inhibited papillary thyroid carcinoma KTC-1 cells growth. DATS treatment triggered a rapid H2 S generation within 5 min in KTC-1 cells. Iodoacetamide, a potent thiol blocker reagent, partially rescued the cell membrane damage and ultimate cell death induced by DATS, indicating H2 S contributed to the apoptosis-inducing efficacy of DATS on thyroid cancer cells. Specifically, DATS treatment significantly upregulated the expression and enzymatic activity of cystathionine gamma-lyase (CTH), one of H2 S-producing enzymes, which was responsible for endogenous H2 S generation. After DATS treatment, H2 S quickly permeated cell membranes and activated NF-κΒ/p65 signaling pathway in KTC-1 cells. Nuclear translocated NF-κB bound to the promoter of CTH to enhance its transcription. These evidences proved that exogenous H2 S elevated CTH expression. CTH, in turn, catalytically generated a much higher level of endogenous H2 S. This positive feedback sustained excess H2 S production, which resulted in PTC cells growth inhibition. These findings may shed light on the development of novel H2 S-based antitumor agents.


Assuntos
Compostos Alílicos/uso terapêutico , Cistationina gama-Liase/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Sulfetos/uso terapêutico , Câncer Papilífero da Tireoide/tratamento farmacológico , Compostos Alílicos/farmacologia , Linhagem Celular Tumoral , Humanos , Inibidores da Agregação de Plaquetas/farmacologia , Sulfetos/farmacologia
8.
Cancer Lett ; 470: 18-28, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31812695

RESUMO

Altered metabolic pathways in cancer such as exacerbated glycolytic flux and increased glutamine metabolism are promising targets for anti-cancer therapies. While commonly observed in glycolytic tumors, extracellular acidosis has never been considered as a potential modulator of anti-metabolic drug activity such as dichloroacetate (DCA). Using cancer cells from various origins selected for their ability to proliferate under acidic conditions, we found that DCA exerts greater inhibitory effects on the growth of these acid-adapted cells than in parental cells. Moreover, daily DCA administration to mice led to a significant decrease in tumor growth from acid-adapted cells but not from parental cells. 13C-tracer studies revealed that DCA induced a double metabolic shift, diminishing glycolysis and increasing intracellular glutamine in acid-adapted cells. As a consequence, DCA reduced the pentose phosphate pathway activity more extensively and increased apoptosis in acid-adapted cells. Finally, the combination of DCA with a glutaminase inhibitor significantly enhanced the cytotoxic effects of DCA. Overall, the interplay between acidosis and DCA exposure leads to metabolic reprogramming that considerably alters cellular fitness.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ácido Dicloroacético/farmacologia , Neoplasias/tratamento farmacológico , Sulfetos/farmacologia , Tiadiazóis/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácido Dicloroacético/uso terapêutico , Sinergismo Farmacológico , Feminino , Glutaminase/antagonistas & inibidores , Glutaminase/metabolismo , Glutamina/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Neoplasias/patologia , Via de Pentose Fosfato/efeitos dos fármacos , /metabolismo , Sulfetos/uso terapêutico , Tiadiazóis/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Mater Sci Eng C Mater Biol Appl ; 107: 110324, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761161

RESUMO

Bismuth (Bi)-based nanoagents for synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) are attracting attention and are highly desired for malignant tumor diagnosis and treatment, but producing these materials is still a challenge. Here, we designed theranostic nanoparticles (NPs) based on AgBiS2 for computed tomography (CT) imaging and phototherapy of malignant tumors. These AgBiS2 NPs could effectively convert light into heat (with a high photothermal conversion efficiency of 36.51%) and significantly increase the generation of intracellular reactive oxygen species (ROS) under near infrared (NIR) laser irradiation. Remarkably, the combined PTT/PDT successfully inhibited the growth of a highly malignant osteosarcoma in vivo. In addition, AgBiS2 NPs exhibited an enhanced CT contrast ability for tumor imaging and killed clinically derived Staphylococcus aureus (S. aureus) to prevent infection. In conclusion the ability of AgBiS2 NPs to be used in phototherapy and CT imaging and their antibacterial abilities indicate that they are promising candidates for malignant tumor theranostics.


Assuntos
Antibacterianos/farmacologia , Nanopartículas Metálicas/uso terapêutico , Fototerapia/métodos , Compostos de Prata/química , Compostos de Prata/uso terapêutico , Sulfetos/química , Sulfetos/uso terapêutico , Animais , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Linhagem Celular Tumoral , Meios de Contraste/química , Meios de Contraste/uso terapêutico , Humanos , Masculino , Nanopartículas Metálicas/química , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/terapia , Osteossarcoma/patologia , Osteossarcoma/terapia , Fotoquimioterapia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificação , Tomografia Computadorizada por Raios X/métodos , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Oncogene ; 39(3): 690-702, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31541193

RESUMO

Many types of cancers have a well-established dependence on glutamine metabolism to support survival and growth, a process linked to glutaminase 1 (GLS) isoforms. Conversely, GLS2 variants often have tumor-suppressing activity. Triple-negative (TN) breast cancer (testing negative for estrogen, progesterone, and Her2 receptors) has elevated GLS protein levels and reportedly depends on exogenous glutamine and GLS activity for survival. Despite having high GLS levels, we verified that several breast cancer cells (including TN cells) express endogenous GLS2, defying its role as a bona fide tumor suppressor. Moreover, ectopic GLS2 expression rescued cell proliferation, TCA anaplerosis, redox balance, and mitochondrial function after GLS inhibition by the small molecule currently in clinical trials CB-839 or GLS knockdown of GLS-dependent cell lines. In several cell lines, GLS2 knockdown decreased cell proliferation and glutamine-linked metabolic phenotypes. Strikingly, long-term treatment of TN cells with another GLS-exclusive inhibitor bis-2'-(5-phenylacetamide-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) selected for a drug-resistant population with increased endogenous GLS2 and restored proliferative capacity. GLS2 was linked to enhanced in vitro cell migration and invasion, mesenchymal markers (through the ERK-ZEB1-vimentin axis under certain conditions) and in vivo lung metastasis. Of concern, GLS2 amplification or overexpression is linked to an overall, disease-free and distant metastasis-free worse survival prognosis in breast cancer. Altogether, these data establish an unforeseen role of GLS2 in sustaining tumor proliferation and underlying metastasis in breast cancer and provide an initial framework for exploring GLS2 as a novel therapeutic target.


Assuntos
Neoplasias da Mama/patologia , Carcinogênese/patologia , Glutaminase/metabolismo , Neoplasias Pulmonares/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzenoacetamidas/farmacologia , Benzenoacetamidas/uso terapêutico , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Técnicas de Silenciamento de Genes , Glutaminase/antagonistas & inibidores , Humanos , Pessoa de Meia-Idade , Prognóstico , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Tiadiazóis/farmacologia , Tiadiazóis/uso terapêutico
11.
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
12.
Chem Commun (Camb) ; 55(87): 13148-13151, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31617549

RESUMO

Cu2ZnSnS4 nanocrystals (CZTS NCs) have been demonstrated to be effective in tumor therapy as a novel susceptible agent for microwave thermal and microwave dynamic therapy. CZTS NCs intensify the heating effect of microwaves with a significant temperature increase of about 15 °C compared to the control group and showed remarkable anti-tumor performance after 5 min of microwave irradiation. For the first time, we report the microwave absorption performance and singlet oxygen production of CZTS NCs used in microwave therapy, which reveals new opportunities for novel combined mechanisms of microwave thermal and microwave dynamic tumor therapies.


Assuntos
Antineoplásicos/uso terapêutico , Cobre/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Micro-Ondas , Nanopartículas/uso terapêutico , Sulfetos/uso terapêutico , Temperatura , Estanho/uso terapêutico , Zinco/uso terapêutico , Animais , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Terapia Combinada , Cobre/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Nanopartículas/química , Tamanho da Partícula , Relação Estrutura-Atividade , Sulfetos/química , Propriedades de Superfície , Estanho/química , Zinco/química
13.
Nanomedicine (Lond) ; 14(17): 2273-2292, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31414615

RESUMO

Aim: Hollow mesoporous copper sulfide nanocapsules conjugated with poly(ethylene glycol) (PEG), doxorubicin and chlorin e6 (HPDC) were synthesized for fluorescence imaging and multimodal tumor therapy. Materials & methods: HPDC were synthesized by encapsulating chlorin e6 and doxorubicin into PEGylated nanocapsules via a simple precipitation method. The photothermal/photodynamic effects, drug release, cellular uptake, imaging capacities and antitumor effects of the HPDCs were evaluated. Results: This smart nanoplatform is stimulus-responsive toward an acidic microenvironment and near infrared laser irradiation. Moreover, fluorescence imaging-guided and combined photothermal/photodynamic/chemotherapies of tumors were promoted under laser activation and led to efficient tumor ablation, as evidenced by exploring animal models in vivo. Conclusion: HPDCs are expected to serve as potent and reliable nanoagents for achieving superior therapeutic outcomes in cancer management.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Doxorrubicina/uso terapêutico , Nanocápsulas/uso terapêutico , Porfirinas/uso terapêutico , Animais , Cobre/uso terapêutico , Feminino , Humanos , Hipertermia Induzida , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Imagem Óptica , Polietilenoglicóis/uso terapêutico , Sulfetos/uso terapêutico , Nanomedicina Teranóstica
14.
Bioorg Med Chem ; 27(19): 115045, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31427145

RESUMO

A novel series of 1,5-diarylpyrrol-3-sulfur derivatives (10-12) was synthesized and characterized by NMR and mass spectroscopy and x-ray diffraction. The biological activity of these compounds was evaluated in in vitro and in vivo tests to assess their COX-2 inhibitory activity along with anti-inflammatory and antinociceptive effect. Results showed that the bioisosteric transformation of previously reported alkoxyethyl ethers (9a-c) into the corresponding alkyl thioethers (10a-c) still leads to selective and active compounds being the COX-2 inhibitory activity for most of them in the low nanomolar range. The oxidation products of 10a,b were also investigated and both couple of sulfoxides (11a,b) and sulfones (12a,b) showed an appreciable COX-2 inhibitory activity. Molecular modeling studies were performed to investigate the binding mode of the representative compounds 10b, 11b, and 12b into COX-2 enzyme and to explore the potential site of metabolism of 10a and 10b due to the different in vivo efficacy. Among the developed compounds, compound 10b showed a significant in vivo anti-inflammatory and antinociceptive activity paving the way to develop novel anti-inflammatory drugs.


Assuntos
Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Pirróis/uso terapêutico , Sulfetos/uso terapêutico , Sulfonas/uso terapêutico , Sulfóxidos/uso terapêutico , Analgésicos/síntese química , Analgésicos/metabolismo , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/uso terapêutico , Carragenina , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/metabolismo , Desenho de Fármacos , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Masculino , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Ligação Proteica , Pirróis/síntese química , Pirróis/metabolismo , Ratos Sprague-Dawley , Ratos Wistar , Relação Estrutura-Atividade , Sulfetos/síntese química , Sulfetos/metabolismo , Sulfonas/síntese química , Sulfonas/metabolismo , Sulfóxidos/síntese química , Sulfóxidos/metabolismo
15.
Naunyn Schmiedebergs Arch Pharmacol ; 392(12): 1561-1568, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31363805

RESUMO

Hydrogen sulfide (H2S) is a vasorelaxant gas with therapeutic potential in several diseases. However, effects of H2S donors in hypertensive pregnancy complicated by feto-placental growth restriction are unclear. Therefore, we aimed to examine and compare the effects of fast-releasing H2S donor (sodium hydrosulfide-NaHS) and slow-releasing H2S donor (GYY4137) in hypertension-in-pregnancy. Pregnant rats were distributed into four groups: normal pregnancy (Norm-Preg), hypertensive pregnancy (HTN-Preg), hypertensive pregnancy + NaHS (HTN-Preg + NaHS), and hypertensive pregnancy + GYY4137 (HTN-Preg + GYY). Systolic blood pressure, plasma H2S levels, fetal and placental weights, number of viable fetuses, litter size, and endothelium-dependent vasodilation were examined. Also, oxidative stress was assessed in placenta. We found that GYY4137 attenuated hypertension on gestational days 16 and 18, while NaHS presented antihypertensive effect only on gestational day 18. GYY4137, but not NaHS, increased plasma H2S levels. Greater fetal and placental weights were found with GYY4137 than NaHS treatment. Also, HTN-Preg + NaHS presented further reductions in placental weights when compared to HTN-Preg group. Number of viable fetuses and litter size presented no significant changes. GYY4137 reduced placental oxidative stress caused by hypertension, while greater increases in oxidative stress were found in HTN-Preg + NaHS than HTN-Preg group. Hypertensive pregnancy caused impaired endothelium-dependent vasodilation, while GYY4137 and NaHS treatments blunted endothelial dysfunction. Endothelium-dependent vasodilation was completely blocked by the nitric oxide synthase inhibitor. We conclude that slow-releasing H2S donor GYY4137 is advantageous compared with fast-releasing H2S-donor NaHS to attenuate hypertension-in-pregnancy and to protect against feto-placental growth restriction and oxidative stress.


Assuntos
Anti-Hipertensivos/uso terapêutico , Retardo do Crescimento Fetal/tratamento farmacológico , Sulfeto de Hidrogênio , Hipertensão/tratamento farmacológico , Morfolinas/uso terapêutico , Compostos Organotiofosforados/uso terapêutico , Sulfetos/uso terapêutico , Animais , Anti-Hipertensivos/metabolismo , Anti-Hipertensivos/farmacologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Feminino , Retardo do Crescimento Fetal/metabolismo , Retardo do Crescimento Fetal/fisiopatologia , Feto/efeitos dos fármacos , Sulfeto de Hidrogênio/sangue , Hipertensão/sangue , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Malondialdeído/metabolismo , Morfolinas/farmacologia , Compostos Organotiofosforados/farmacologia , Placenta/efeitos dos fármacos , Gravidez , Ratos Wistar , Sulfetos/farmacologia
16.
J Pharmacol Sci ; 140(2): 162-170, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31285125

RESUMO

QTc prolongation has been observed during arsenic trioxide and realgar's clinical use, and become a huge obstacle for the application. Our lab has obtained the soluble arsenic from realgar named realgar transforming solution or RTS. In this study, we first evaluated the cytotoxicity on NB4 cell and found that RTS could remarkably inhibit proliferation of NB4 than arsenic trioxide. Then we figured out the QTc prolongation of RTS treatment contrasted with arsenic trioxide; results revealed that arsenic trioxide prolonged corrected QTc of mice by 20.1% and showed 1.9-fold higher cytotoxicity on H9c2 cell than RTS. On the contrary, there could not find any QTc prolongation of mice in RTS treatment. Also, arsenic trioxide elevated the intercellular calcium accumulation of H9c2 cell by 2.02-fold v.s control and RTS. HE staining and Masson's trichrome staining had shown that there was no injured section after RTS treatments. IK1 currents of rat ventricular cardiomyocytes were diminished by 45.0% after treating with arsenic trioxide while RTS showed no significance than the control group. The results above indicated that RTS could serve as an alternative arsenic agent on leukemia and had a lower risk of cardiotoxicity.


Assuntos
Arsenicais , Cardiotoxicidade/etiologia , Sulfetos/toxicidade , Animais , Arsenicais/efeitos adversos , Arsenicais/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Leucemia/tratamento farmacológico , Síndrome do QT Longo/induzido quimicamente , Masculino , Camundongos , Ratos Wistar , Risco , Soluções , Sulfetos/efeitos adversos , Sulfetos/uso terapêutico
17.
Mol Cell Biochem ; 460(1-2): 151-164, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31280436

RESUMO

Diallyl trisulfide (DATS) is distinguished as the most potent polysulfide isolated from garlic. The aim of our study was to investigate effects of oral administration of DATS on healthy and diabetic rats, with special attention on heart function. Rats were randomly divided into four groups: CTRL (healthy rats), DATS (healthy rats treated with DATS), DM (diabetic rats), DM + DATS (diabetic rats treated with DATS). DATS (40 mg/kg of body weight) was administered every other day for 3 weeks, at the end of which rats underwent echocardiography, glycemic measurement and redox status assessment. Isolated rat hearts were subjected to 30 min global ischemia and 60 min reperfusion, after which heart tissue was counterstain with hematoxylin and eosin and cardiac Troponin T staining (cTnT), while expression of Bax, B cell lymphoma 2 (Bcl-2), caspase-3, caspase-9 and superoxide dismutase-2 were examined in the left ventricle. DATS treatment significantly reduced blood glucose levels of diabetic rats, and improved cardiac function recovery, diminished oxidation status, attenuated cardiac remodeling and inhibited myocardial apoptosis in healthy and diabetic rats. DATS treatment causes promising cardioprotective effects on ex vivo-induced ischemia/reperfusion (I/R) injury in diabetic and healthy rat heart probably mediated by inhibited myocardial apoptosis. Moreover, appropriate DATS consumption may provide potential co-therapy or prevention of hyperglycemia and various cardiac complications in rats with DM.


Assuntos
Compostos Alílicos/uso terapêutico , Cardiotônicos/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Sulfetos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Cardiotônicos/farmacologia , Diabetes Mellitus Experimental/fisiopatologia , Masculino , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia
18.
Iran J Immunol ; 16(2): 170-181, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31182691

RESUMO

BACKGROUND: Realgar, an arsenic tetrasulfide compound, is a highly recognized traditional Chinese medicinal prescription that has been widely used to treat various diseases such as inflammatory diseases. However, there are still some problems in the clinical treatment of Realgar, such as large oral dose and high potential toxicity. OBJECTIVE: To evaluate effects of Realgar nanoparticles on lupus nephritis (LN) in vivo in MRL/lpr mice. METHODS: Ten-week mice were orally administered every day for eight consecutive weeks except the mice of normal model groups. The serum levels of anti-ds-DNA antibody IgG, IgM, IFN-γ, Creatinine (Cr), and blood urea nitrogen (BUN) were determined, and 24-hour urine protein was also measured. Renal inflammatory pathology analysis was assessed by hematoxylin-eosin (H&E) staining. The expression of phosphorylated signal transducer and activator of transcription 1 (p-STAT 1) and Janus Kinase 1 (JAK 1) in kidney tissue was determined by direct reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). RESULTS: The mice treated with Realgar nanoparticle in the high dose-treated (Realgar HD, 0.03 g/kg/d) group exhibited significantly reduced serum levels of anti-dsDNA (p<0.01), IgG (p<0.01), IgM (p<0.01), BUN (p<0.01), Cr (p<0.01), and inflammatory cytokine IFN-γ (p<0.01) as well as proteinuria (p<0.01) compared to the untreated model MRL/lpr mice. Additionally, high doses of Realgar nanoparticles significantly suppressed the phosphorylations of STAT 1(p<0.01) and the renal pathological changes. CONCLUSIONS: The study indicates that Realgar nanoparticles may be a potential agent to treat LN, and the down-regulated p-STAT1 expression suggests that it may be one of the LN treatment targets for Realgar nanoparticles.


Assuntos
Arsenicais/uso terapêutico , Rim/patologia , Nefrite Lúpica/terapia , Nanopartículas/uso terapêutico , Fator de Transcrição STAT1/metabolismo , Sulfetos/uso terapêutico , Animais , Arsenicais/química , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Janus Quinase 1/metabolismo , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos MRL lpr , Nanopartículas/química , Transdução de Sinais , Sulfetos/química
19.
Metab Brain Dis ; 34(5): 1313-1324, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31177357

RESUMO

The present study investigated a possible antidepressant-like effect of ((4-tert-butylcyclohexylidene)methyl) (4-methoxystyryl) sulfide (BMMS) by using the forced swimming test (FST) and the tail suspension test (TST) in Swiss mice. The contribution of serotoninergic, glutamatergic and nitrergic systems in the antidepressant-like activity of BMMS was evaluated. We also examined the involvement of monoamine oxidase (MAO)-A, MAO-B and Na+, K+-ATPase activities in prefrontal cortex of mice. BMMS, (0.1-10 mg/kg, intragastrically (i.g.)) and fluoxetine (32 mg/kg, i.g.) decreased the immobility time in the FST and TST. The anti-immobility effect of BMMS (10 mg/kg, i.g.) in the TST was prevented by the pretreatment of mice with WAY100635 (0.1 mg/kg, subcutaneously (s.c.), a 5-HT1A receptor antagonist), ketanserin (5 mg/kg, intraperitoneal (i.p.), a 5-HT2A/2C receptor antagonist), and partially blocked by ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). The anti-immobility effect of BMMS (10 mg / kg, i.g.) was not avoided by pretreatment with MK-801 (0.01 mg/kg, s.c. a non-competitive N-methyl D-Aspartate (NMDA) receptor) in the TST. Pretreatment with L-arginine (500 mg/kg, i.p., a nitric oxide precursor) reversed partially the reduction in the immobility time elicited by BMMS (10 mg/kg, i.g.) in TST. BMMS altered Na+,K+-ATPase and MAO-A activities in prefrontal cortex of mice, but was not able to change the MAO-B activity. In conclusion, BMMS exerted an antidepressant-like effect in mice and serotonergic and nitrergic systems are involved in the antidepressant-like action of compound. BMMS modulated MAO-A and Na+, K+- ATPase activities in prefrontal cortex of mice.


Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Óxido Nítrico/metabolismo , Serotonina/metabolismo , Estirenos/farmacologia , Sulfetos/farmacologia , Animais , Antidepressivos/uso terapêutico , Arginina/farmacologia , Comportamento Animal/efeitos dos fármacos , Depressão/metabolismo , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/farmacologia , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Elevação dos Membros Posteriores , Masculino , Camundongos , Monoaminoxidase/metabolismo , Atividade Motora/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Antagonistas da Serotonina/farmacologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Estirenos/uso terapêutico , Sulfetos/uso terapêutico
20.
Eur J Clin Pharmacol ; 75(10): 1355-1360, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31243478

RESUMO

OBJECTIVE: Renal insufficiency may influence the pharmacokinetics of drugs. We have investigated the pharmacokinetic parameters of imrecoxib and its two main metabolites in individuals with osteoarthritis (OA) with normal renal function and renal insufficiency, respectively. METHODS: This was a prospective, parallel, open, matched-group study in which 24 subjects were enrolled (renal insufficiency group, n = 12; healthy control group, n = 12). Blood samples of subjects administered 100 mg imrecoxib were collected at different time points and analyzed. Plasma concentrations of imrecoxib and its two metabolites (M1 and M2) were determined by the liquid chromatography-tandem mass spectrometry method, and pharmacokinetic parameters (clearance [CL], apparent volume of distribution [Vd], maximum (or peak) serum concentration [Cmax], amount of time drug is present in serum at Cmax [Tmax], area under the curve [AUC; total drug exposure across time], mean residence time [MRT] and elimination half-life [t1/2]) were calculated. RESULTS: The demographic characteristics of the two groups were not significantly different, with the exception of renal function. The mean Cmax and AUC0-t (AUC from time 0 to the last measurable concentration) of imrecoxib in the renal insufficiency group were 59 and 70%, respectively, of those of the healthy control volunteers with normal renal function, indicating a significant decline in the former group (P < 0. 05). The mean pharmacokinetic parameters of Ml in the renal insufficiency and healthy control groups did not significantly differ. In contrast, the mean Cmax and AUC0-t of M2 in the renal insufficiency group were 233 and 367%, respectively, of those of the normal renal function group, indicating a significant increase in the former group (P < 0.05). The mean CL/F (clearance/bioavailability) of M2 of the renal insufficiency group was 37% of that of the normal renal function group, indicating a notable reduction in the former group (P < 0.05). CONCLUSION: The exposure of imrecoxib in OA patients with renal insufficiency showed a decline compared to that in healthy subjects. However, in patients with renal insufficiency the exposure of M2 was markedly increased and the CL was noticeably reduced. These results indicate that the dosage of imrecoxib should be reduced appropriately in patients with renal insufficiency.


Assuntos
Inibidores de Ciclo-Oxigenase 2/farmacocinética , Pirróis/farmacocinética , Insuficiência Renal/metabolismo , Sulfetos/farmacocinética , Adulto , Idoso , Inibidores de Ciclo-Oxigenase 2/sangue , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Pirróis/sangue , Pirróis/uso terapêutico , Insuficiência Renal/tratamento farmacológico , Sulfetos/sangue , Sulfetos/uso terapêutico
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