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1.
Chem Biol Interact ; 399: 111149, 2024 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-39032852

RESUMO

Rhabdomyosarcoma (RMS) represents one of the most lethal soft-tissue sarcomas in children. The toxic trace element arsenic has been reported to function as a radiosensitizer in sarcomas. To investigate the role of arsenic sulfide (As4S4) in enhancing radiation sensitization in RMS, this study was conducted to elucidate its underlying mechanism in radiotherapy. The combination of As4S4 and radiotherapy showed significant inhibition in RMS cells, as demonstrated by the cell counting kit-8 (CCK-8) assay and flow cytometry. Subsequently, we demonstrated for the first time that As4S4, as well as the knockdown of NFATc3 led to double-strand break (DSB) through increased expression of RAG1. In vivo experiment confirmed that co-treatment efficiently inhibited RMS growth. Furthermore, survival analysis of a clinical cohort consisting of 59 patients revealed a correlation between NFATc3 and RAG1 expression and overall survival (OS). Cox regression analysis also confirmed the independent prognostic significance of NFATc3 and RAG1.Taken together, As4S4 enhances radiosensitivity in RMS via activating NFATc3-RAG1 mediated DSB. NFATc3 and RAG1 are potential therapeutic targets. As4S4 will hopefully serve as a prospective radio-sensitizing agent for RMS.


Assuntos
Arsenicais , Quebras de DNA de Cadeia Dupla , Fatores de Transcrição NFATC , Tolerância a Radiação , Rabdomiossarcoma , Sulfetos , Humanos , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Quebras de DNA de Cadeia Dupla/efeitos da radiação , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Rabdomiossarcoma/metabolismo , Rabdomiossarcoma/tratamento farmacológico , Rabdomiossarcoma/radioterapia , Rabdomiossarcoma/patologia , Rabdomiossarcoma/genética , Linhagem Celular Tumoral , Masculino , Feminino , Arsenicais/farmacologia , Arsenicais/uso terapêutico , Animais , Tolerância a Radiação/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Camundongos , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Camundongos Nus , Criança , Radiossensibilizantes/farmacologia , Radiossensibilizantes/uso terapêutico , Camundongos Endogâmicos BALB C
2.
Front Immunol ; 15: 1279043, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38840916

RESUMO

Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature female worms that are trapped in host's tissues, resulting in chronic Th2 driven fibrogranulmatous pathology. Although the disease can be treated with a relatively inexpensive drug, praziquantel (PZQ), re-infections remain a major problem in endemic areas. There is a need for new therapeutic drugs and alternative drug treatments for schistosomiasis. The current study hypothesized that cysteinyl leukotrienes (cysLTs) could mediate fibroproliferative pathology during schistosomiasis. Cysteinyl leukotrienes (cysLTs) are potent lipid mediators that are known to be key players in inflammatory diseases, such as asthma and allergic rhinitis. The present study aimed to investigate the role of cysLTR1 during experimental acute and chronic schistosomiasis using cysLTR1-/- mice, as well as the use of cysLTR1 inhibitor (Montelukast) to assess immune responses during chronic Schistosoma mansoni infection. Mice deficient of cysLTR1 and littermate control mice were infected with either high or low dose of Schistosoma mansoni to achieve chronic or acute schistosomiasis, respectively. Hepatic granulomatous inflammation, hepatic fibrosis and IL-4 production in the liver was significantly reduced in mice lacking cysLTR1 during chronic schistosomiasis, while reduced liver pathology was observed during acute schistosomiasis. Pharmacological blockade of cysLTR1 using montelukast in combination with PZQ reduced hepatic inflammation and parasite egg burden in chronically infected mice. Combination therapy led to the expansion of Tregs in chronically infected mice. We show that the disruption of cysLTR1 is dispensable for host survival during schistosomiasis, suggesting an important role cysLTR1 may play during early immunity against schistosomiasis. Our findings revealed that the combination of montelukast and PZQ could be a potential prophylactic treatment for chronic schistosomiasis by reducing fibrogranulomatous pathology in mice. In conclusion, the present study demonstrated that cysLTR1 is a potential target for host-directed therapy to ameliorate fibrogranulomatous pathology in the liver during chronic and acute schistosomiasis in mice.


Assuntos
Acetatos , Ciclopropanos , Modelos Animais de Doenças , Camundongos Knockout , Quinolinas , Receptores de Leucotrienos , Esquistossomose mansoni , Sulfetos , Animais , Receptores de Leucotrienos/metabolismo , Camundongos , Ciclopropanos/uso terapêutico , Ciclopropanos/farmacologia , Acetatos/uso terapêutico , Acetatos/farmacologia , Sulfetos/uso terapêutico , Sulfetos/farmacologia , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/imunologia , Esquistossomose mansoni/parasitologia , Quinolinas/uso terapêutico , Quinolinas/farmacologia , Feminino , Schistosoma mansoni/imunologia , Doença Crônica , Antagonistas de Leucotrienos/farmacologia , Antagonistas de Leucotrienos/uso terapêutico , Fígado/parasitologia , Fígado/patologia , Fígado/metabolismo , Fígado/imunologia , Camundongos Endogâmicos C57BL , Praziquantel/uso terapêutico , Praziquantel/farmacologia , Linfócitos T Reguladores/imunologia
3.
Eur J Pharmacol ; 978: 176755, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38909933

RESUMO

Cysteinyl leukotrienes (CysLTs) are central to the pathophysiology of asthma and various inflammatory disorders. Leukotriene receptor antagonists (LTRAs) effectively treat respiratory conditions by targeting cysteinyl leukotriene receptors, CysLT1 and CysLT2 subtypes. This review explores the multifaceted effects of LTs, extending beyond bronchoconstriction. CysLT receptors are not only present in the respiratory system but are also crucial in neuronal signaling pathways. LTRAs modulate these receptors, influencing downstream signaling, calcium levels, inflammation, and oxidative stress (OS) within neurons hinting at broader implications. Recent studies identify novel molecular targets, sparking interest in repurposing LTRAs for therapeutic use. Clinical trials are investigating their potential in neuroinflammation control, particularly in Alzheimer's disease (AD) and Parkinson's diseases (PD). However, montelukast, a long-standing LTRA since 1998, raises concerns due to neuropsychiatric adverse drug reactions (ADRs). Despite widespread use, understanding montelukast's metabolism and underlying ADR mechanisms remains limited. This review comprehensively examines LTRAs' diverse biological effects, emphasizing non-bronchoconstrictive activities. It also analyses plausible mechanisms behind LTRAs' neuronal effects, offering insights into their potential as neurodegenerative disease modulators. The aim is to inform clinicians, researchers, and pharmaceutical developers about LTRAs' expanding roles, particularly in neuroinflammation control and their promising repurposing for neurodegenerative disease management.


Assuntos
Antagonistas de Leucotrienos , Receptores de Leucotrienos , Humanos , Antagonistas de Leucotrienos/uso terapêutico , Antagonistas de Leucotrienos/farmacologia , Antagonistas de Leucotrienos/efeitos adversos , Animais , Receptores de Leucotrienos/metabolismo , Sulfetos/uso terapêutico , Sulfetos/farmacologia , Sulfetos/efeitos adversos , Acetatos/uso terapêutico , Acetatos/farmacologia , Acetatos/efeitos adversos , Neurotransmissores/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ciclopropanos , Quinolinas
4.
Cell Mol Biol (Noisy-le-grand) ; 70(5): 59-68, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38814234

RESUMO

Development of novel functional foods is trending as one of the hot topics in food science and food/beverage industries. In the present study, the anti-diabetic, anti-hyperlipidemic and histo-protective effects of the extra virgin olive oil (EVOO) enriched with the organosulfur diallyl sulfide (DAS) (DAS-rich EVOO) were evaluated in alloxan-induced diabetic mice. The ingestion of EVOO (500µL daily for two weeks) attenuated alloxan-induced elevated glucose, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase (LDH), urea and creatinine. It also normalized the levels of triglycerides (TG), total cholesterols (TC), low-density lipoprotein-cholesterol (LDL-c) and their consequent atherogenic index of plasma (AIP) in diabetic animals. Additionally, EVOO prevented lipid peroxidation (MDA) and reduced the level of hydrogen peroxide (H2O2) in diabetic animals. Concomitantly, it enhanced the activity of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), reducing thereby tissue oxidative stress injury. The overall histologic (pancreas, liver, and kidney) alterations were also improved after EVOO ingestion. The manifest anti-diabetic, lipid-lowering and histo-protective properties of EVOO were markedly potentiated with DAS-rich EVOO suggesting possible synergistic interactions between DAS and EVOO lipophilic bioactive ingredients. Overall, EVOO and DAS-rich EVOO show promise as functional foods and/or adjuvants for the treatment of diabetes and its complications.


Assuntos
Compostos Alílicos , Diabetes Mellitus Experimental , Hipoglicemiantes , Hipolipemiantes , Azeite de Oliva , Sulfetos , Animais , Azeite de Oliva/química , Azeite de Oliva/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Compostos Alílicos/farmacologia , Compostos Alílicos/uso terapêutico , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Sulfetos/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Camundongos , Hipolipemiantes/farmacologia , Masculino , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pâncreas/metabolismo , Glutationa Peroxidase/metabolismo , Catalase/metabolismo , Peróxido de Hidrogênio/metabolismo , Superóxido Dismutase/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/sangue , Triglicerídeos/sangue , Triglicerídeos/metabolismo
5.
J Ethnopharmacol ; 331: 118303, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38734390

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar, a traditional mineral Chinese medicine, has been used in China for more than 2000 years. It has been recorded in many ancient and modern works that it has anti-cancer and anti-tumor effects. Of course, colon cancer is also within the scope of its treatment. Realgar needs to be processed into realgar decoction pieces by water grinding before being used for medicine. To ensure the consistency of efficacy and quality of realgar decoction pieces, modern methods need to be used for further quality control. AIM OF THE STUDY: The research of traditional mineral Chinese medicine is relatively difficult, and the related research is less. The purpose of this study is to control the quality of realgar decoction pieces by modern analytical technology and analyze its components. On this basis, its anti-colon cancer activity was discussed. MATERIALS AND METHODS: Several batches of realgar decoction pieces were analyzed by XRD, and the components of realgar decoction pieces were obtained. The quality control fingerprints of realgar decoction pieces were established by processing XRD spectra and similarity evaluation. Then, the effects of realgar decoction pieces on apoptosis of CT26 and HTC-116 cells were observed in vitro by Hoechst 33258 staining, flow cytometry, measurement of mitochondrial membrane potential and Western blot; In vivo, the mouse model of tumor-in-situ transplantation of colon cancer was established, and the related indexes were observed. RESULT: The explorations showed that the XRD Fourier fingerprints of realgar decoction pieces samples that had the same phase revealed 10 common peaks, respectively. The similarity evaluation of the established XRD Fourier fingerprint was greater than 0.900. We also demonstrated that realgar decoction pieces can promote apoptosis and inhibit tumor growth in colon cancer cells, its activating effect on p53 protein, and its safety when used within reasonable limits. CONCLUSION: The quality control of realgar decoction pieces by XRD is scientific and has the inhibitory effect on colon cancer, which has the development potential.


Assuntos
Apoptose , Neoplasias do Colo , Animais , Apoptose/efeitos dos fármacos , Camundongos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Humanos , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Arsenicais/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Masculino , Controle de Qualidade , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico
6.
Vet Parasitol ; 329: 110211, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772086

RESUMO

Ticks, particularly Rhipicephalus annulatus, pose significant threats to livestock, causing economic losses and transmitting various infectious diseases. This study aimed to evaluate the potential acaricidal properties of garlic oil and its nanoemulsion against ticks infesting cattle, Rhipicephalus annulatus through the evaluation of mortality rate and morphological changes of the treated ticks. The study also included prevalence, risk factors, and molecular confirmation of tick species. Genetic characterization confirmed the identity of R. annulatus. Our results revealed a high prevalence of R. annulatus (46.9%) with a higher risk in male cattle (50%) than females (44.9%) and a nonsignificant high infection (49.1%) in animals ≤ 1 year old. The acaricidal efficiency of garlic oil and its nanoemulsion was concentration and time-dependent. The high concentration of garlic oil (20 mg/L) induced complete mortality within 48 hours. The nanoemulsion formulation enhanced efficacy, particularly at 5 mg/L, which exhibited rapid and substantial acaricidal activity. Scanning electron microscopy revealed morphological alterations induced by garlic oil and its nanoemulsion, including changes to the anterior capitulum, dorsal, and ventral cuticles. The study contributes to the exploration of effective, safe, and eco-friendly alternatives for tick control. Further research is warranted to validate their efficacy under diverse conditions and assess practical strategies.


Assuntos
Acaricidas , Doenças dos Bovinos , Emulsões , Rhipicephalus , Infestações por Carrapato , Animais , Acaricidas/farmacologia , Infestações por Carrapato/veterinária , Infestações por Carrapato/parasitologia , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/prevenção & controle , Doenças dos Bovinos/parasitologia , Doenças dos Bovinos/tratamento farmacológico , Feminino , Bovinos , Masculino , Rhipicephalus/efeitos dos fármacos , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Compostos Alílicos/farmacologia , Alho/química
7.
Aging (Albany NY) ; 16(7): 6521-6536, 2024 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-38613798

RESUMO

Acute lung injury (ALI) is a major cause of acute respiratory failure with a high morbidity and mortality rate, and effective therapeutic strategies for ALI remain limited. Inflammatory response is considered crucial for the pathogenesis of ALI. Garlic, a globally used cooking spice, reportedly exhibits excellent anti-inflammatory bioactivity. However, protective effects of garlic against ALI have never been reported. This study aimed to investigate the protective effects of garlic oil (GO) supplementation on lipopolysaccharide (LPS)-induced ALI models. Hematoxylin and eosin staining, pathology scores, lung myeloperoxidase (MPO) activity measurement, lung wet/dry (W/D) ratio detection, and bronchoalveolar lavage fluid (BALF) analysis were performed to investigate ALI histopathology. Real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were conducted to evaluate the expression levels of inflammatory factors, nuclear factor-κB (NF-κB), NLRP3, pyroptosis-related proteins, and H2S-producing enzymes. GO attenuated LPS-induced pulmonary pathological changes, lung W/D ratio, MPO activity, and inflammatory cytokines in the lungs and BALF. Additionally, GO suppressed LPS-induced NF-κB activation, NLRP3 inflammasome expression, and inflammatory-related pyroptosis. Mechanistically, GO promoted increased H2S production in lung tissues by enhancing the conversion of GO-rich polysulfide compounds or by increasing the expression of H2S-producing enzymes in vivo. Inhibition of endogenous or exogenous H2S production reversed the protective effects of GO on ALI and eliminated the inhibitory effects of GO on NF-κB, NLRP3, and pyroptotic signaling pathways. Overall, these findings indicate that GO has a critical anti-inflammatory effect and protects against LPS-induced ALI by suppressing the NF-κB/NLRP3 signaling pathway via H2S generation.


Assuntos
Lesão Pulmonar Aguda , Compostos Alílicos , Sulfeto de Hidrogênio , Lipopolissacarídeos , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Transdução de Sinais , Sulfetos , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , NF-kappa B/metabolismo , Piroptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Compostos Alílicos/farmacologia , Compostos Alílicos/uso terapêutico , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Masculino , Sulfeto de Hidrogênio/metabolismo , Camundongos , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Alho/química , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , Suplementos Nutricionais
8.
Braz J Otorhinolaryngol ; 90(3): 101399, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38442638

RESUMO

OBJECTIVES: Montelukast is a well-known leukotriene receptor antagonist commonly used in treating allergic rhinitis and asthma. Omega-3 fatty acid is also known as an antiallergic and immunomodulator molecule. This study aimed to elucidate the efficacy of systemic montelukast and omega-3 fatty acid treatment in allergic rhinitis models in Wistar Hannover rats. METHODS: This research was conducted on 28 healthy Wistar Hannover rats weighing 250-350 g. After establishing the allergic rhinitis model, nasal symptoms were observed and scored, and the nasal mucosa of all rats was investigated histologically. Light microscopy was utilized to evaluate the degree of ciliary loss, goblet cell hyperplasia, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration, and hypertrophy in chondrocytes. RESULTS: As a result of the analysis of the data obtained from the study, it was determined that typical allergic rhinitis symptoms such as nasal scratching and sneezing were significantly reduced in the rats in the montelukast and omega-3 treated group, and these symptoms did not increase after repeated intranasal OVA-protease applications. Histological examinations after fish oil treatment did not reveal typical inflammatory changes in allergic rhinitis. None of the rats in the montelukast and omega-3 groups had any increase in goblet cells, whereas 14.3% of the rats in the control group and 28.6% of the rats in the allergic rhinitis group had mild increase. Last but not least, 71.4% of rats in the allergic rhinitis group had a moderate increase. The difference between the groups was statistically significant (p < 0.001). CONCLUSION: Regarding the outcomes of this research, it was observed that w-3 fatty acids had antiallergic effects, both histopathological and clinical, in the allergic rhinitis model. We believe that further randomized controlled trials incorporating larger cohorts are warranted to verify the use of omega-3 fatty acids in treating allergic rhinitis. The level of evidence of this article is Level 2.


Assuntos
Acetatos , Ciclopropanos , Modelos Animais de Doenças , Ácidos Graxos Ômega-3 , Óleos de Peixe , Antagonistas de Leucotrienos , Ovalbumina , Quinolinas , Ratos Wistar , Rinite Alérgica , Sulfetos , Animais , Ciclopropanos/uso terapêutico , Sulfetos/uso terapêutico , Acetatos/uso terapêutico , Quinolinas/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/patologia , Ratos , Antagonistas de Leucotrienos/uso terapêutico , Óleos de Peixe/uso terapêutico , Masculino , Resultado do Tratamento , Mucosa Nasal/patologia , Mucosa Nasal/efeitos dos fármacos
9.
J Ethnopharmacol ; 326: 117778, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38310990

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In China, the Chinese patent drug Realgar-Indigo naturalis Formula (RIF) is utilized for the therapy of acute promyelocytic leukemia (APL). Comprising four traditional Chinese herb-Realgar, Indigo naturalis, Salvia miltiorrhiza, and Pseudostellaria heterophylla-it notably includes tetra-arsenic tetra-sulfide, indirubin, tanshinone IIa, and total saponins of Radix Pseudostellariae as its primary active components. Due to its arsenic content, RIF distinctly contributes to the therapy for APL. However, the challenge of arsenic resistance in APL patients complicates the clinical use of arsenic agents. Interestingly, RIF demonstrates a high remission rate in APL patients, suggesting that its efficacy is not significantly compromised by arsenic resistance. Yet, the current state of research on RIF's ability to reverse arsenic resistance remains unclear. AIM OF THE STUDY: To investigate the mechanism of different combinations of the compound of RIF in reversing arsenic resistance in APL. MATERIALS AND METHODS: The present study utilized the arsenic-resistant HL60-PMLA216V-RARα cell line to investigate the effects of various RIF compounds, namely tetra-arsenic tetra-sulfide (A), indirubin (I), tanshinone IIa (T), and total saponins of Radix Pseudostellariae (S). The assessment of cell viability, observation of cell morphology, and evaluation of cell apoptosis were performed. Furthermore, the mitochondrial membrane potential, changes in the levels of PMLA216V-RARα, apoptosis-related factors, and the PI3K/AKT/mTOR pathway were examined, along with autophagy in all experimental groups. Meanwhile, we observed the changes about autophagy after blocking the PI3K or mTOR pathway. RESULTS: Tanshinone IIa, indirubin and total saponins of Radix Pseudostellariae could enhance the effect of tetra-arsenic tetra-sulfide down-regulating PMLA216V-RARα, and the mechanism was suggested to be related to inhibiting mTOR pathway to activate autophagy. CONCLUSIONS: We illustrated that the synergistic effect of different compound combinations of RIF can regulate autophagy through the mTOR pathway, enhance cell apoptosis, and degrade arsenic-resistant PMLA216V-RARα.


Assuntos
Abietanos , Arsênio , Arsenicais , Medicamentos de Ervas Chinesas , Leucemia Promielocítica Aguda , Saponinas , Humanos , Arsênio/efeitos adversos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/induzido quimicamente , Fosfatidilinositol 3-Quinases , Arsenicais/farmacologia , Arsenicais/uso terapêutico , Sulfetos/farmacologia , Sulfetos/uso terapêutico , Saponinas/uso terapêutico
10.
Int Immunopharmacol ; 127: 111373, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38128310

RESUMO

Cisplatin, a chemotherapy medication employed in the treatment of various solid tumors, is constrained in its clinical application due to nephrotoxicity. Diallyl trisulfide (DATS), a compound derived from garlic that possessed anticancer and antioxidant properties, can be combined with cisplatin without hindering its antitumor effects. The present investigation examined the defensive properties of DATS and its active metabolites against renal dysfunction caused by cisplatin. We created a mouse model to study renal injury caused by cisplatin and assessed kidney histology, immunochemistry, and serum cytokines. DATS treatment effectively reduced the pathological changes caused by cisplatin by decreasing the levels of renal function markers BUN, CRE, cystatin C, NGAL, inflammatory factors TNF-α, IL-6, and the protein expression of α-SMA, NF-κB, KIM-1. A pharmacokinetic evaluation of DATS found that allyl methyl sulfone (AMSO2) was the most abundant and persistent metabolite of DATS in vivo. Then, we examined the impact of AMSO2 on cell viability, apoptosis, ROS generation, and MAPK/NF-κB pathways in HK-2 cells treated with cisplatin. Cotreatment with AMSO2 effectively hindered the HK-2 cells alterations induced by cisplatin. Furthermore, AMSO2 mitigated oxidative stress through the modulation of MAPK and NF-κB pathways. Our findings indicated that DATS and its active derivative AMSO2 attenuated cisplatin-induced nephrotoxicity. DATS shows potential as a viable treatment for nephrotoxicity caused by cisplatin.


Assuntos
Compostos Alílicos , Cisplatino , Dimetil Sulfóxido , Sulfonas , Camundongos , Animais , Cisplatino/farmacologia , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Compostos Alílicos/farmacologia , Compostos Alílicos/uso terapêutico , Sulfetos/uso terapêutico , Sulfetos/farmacologia , Apoptose , Antioxidantes/farmacologia
11.
Nanomedicine (Lond) ; 18(30): 2185-2204, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38116732

RESUMO

Copper sulfide nanoparticles (CuS NPs) have attracted growing interest in biomedical research due to their remarkable properties, such as their high photothermal and thermodynamic capabilities, which are ideal for anticancer and antibacterial applications. This comprehensive review focuses on the current state of antitumor and antibacterial applications of CuS NPs. The initial section provides an overview of the various approaches to synthesizing CuS NPs, highlighting the size, shape and composition of CuS NPs fabricated using different methods. In this review, the mechanisms underlying the antitumor and antibacterial activities of CuS NPs in medical applications are discussed and the clinical challenges associated with the use of CuS NPs are also addressed.


Assuntos
Infecções Bacterianas , Nanopartículas , Neoplasias , Humanos , Cobre/uso terapêutico , Fototerapia , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Sulfetos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Antibacterianos/uso terapêutico
12.
Rev. bras. parasitol. vet ; 30(1): e015920, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1156210

RESUMO

Abstract 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.


Resumo O consumo de peixe inadequadamente tratado termicamente representa um risco para a saúde pública, com a possibilidade da propagação de larvas de Anisakis. O presente estudo demonstrou as alterações fisiológicas e histopatológicas acompanhadas de inoculação oral de extractos brutos de Anisakis tipo II (L3) frescos e termicamente tratados em ratos. Os vermes foram isolados de um peixe marinho, examinados e identificados por microscopia de luz e eletrônica de varredura. O estudo foi conduzido em 6 grupos de ratos: controle (I), óleo de alho (GO) inoculado (II), L3 fresco inoculado (III), L3 tratado termicamente inoculado (IV), L3 fresco + GO inoculado (V), e um grupo L3 + GO tratado termicamente inoculado (VI). Observou-se que ratos inoculados com L3 fresco e tratados termicamente mostraram funções hepáticas e renais anormais, associadas à destruição da sua arquitetura normal. GO produziu um efeito protector em grupos de ratos inoculados com extractos L3 + GO através da melhoria das funções do fígado e dos rins, o que foi confirmado pela estrutura normal marcada da sua histologia. A cozedura de peixes infectados com L3 induziu alterações mais graves do que os peixes não cozidos. Recomenda-se a administração de alho antes e depois do consumo de peixe, para evitar o efeito perigoso dos anisakids, mesmo que sejam cozidos.


Assuntos
Animais , Ratos , Sulfetos/farmacologia , Anisakis/efeitos dos fármacos , Anisaquíase/prevenção & controle , Anisaquíase/tratamento farmacológico , Compostos Alílicos/uso terapêutico , Compostos Alílicos/farmacologia , Sulfetos/uso terapêutico , Parasitologia de Alimentos , Ratos Wistar , Culinária , Peixes/parasitologia , Larva , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/farmacologia
13.
West Indian med. j ; 56(1): 17-21, Jan. 2007.
Artigo em Inglês | LILACS | ID: lil-471843

RESUMO

The data compiled in the present review on dibenzyl trisulphide (DTS) isolated from Petiveria alliacea L (the guinea hen weed or anamu) revealed that the compound and its derivatives could be of tremendous pharmaceutical interest. The mode of action elucidated for DTS revealed that it is a mitogen activated protein extracellular regulated kinases 1 and 2 (MAPKinases erk1 and erk 2) signal transduction molecule. Dibenzyl trisulphide caused hyper-phosphorylation of growth factor induced MAPKinases (erk 1 and erk 2) phosphorylation, a process critical for the improvement of long term memory, and is implicated in neuronal growth. Dibenzyl trisulphide and its derivatives exhibited potent anti-proliferation/cytotoxic activity on a wide range of cancer cell lines. The cytotoxic activity of DTS was increased by 70-1000 fold when bound to albumin in vitro. Dibenzyl trisulphide seems to have a cytokine switching mechanism in which it down regulates cytokines from the Type I helper cells (Th -1 cell) pathway which contained several pro-inflammatory cytokines and up-regulates those on the Type 2 helper cells (Th-2) pathway. The trisulphide up-regulates some reticuloendothelial system parameters eg granulocyte counts and increased thymic and Peyer's patches masses via cell proliferation processes which are known to be regulated via the MAPKinase signal transduction pathway. When the zygotes ofAsternia pectinifera (Starfish) were exposed to DTS at concentration of 10 mM, a dose lethal to all cancer cells tested, it was observed that the sensitive process of protein biosynthesis was not affected Similarly, the proliferation of the HOFA human fibroblast, a noncancerous cell line, was not severely affected by DTS at 8.9 microM over seven days, a concentration also lethal to most cancer cell lines tested The implications of the findings will be highlighted in the present review.


Los datos compilados en el presente estudio sobre el trisulfuro de dibencilo (TSD) aislado a partir de Petiveria alliacea L (yerba de Guinea, ó anamú) revelaron que el compuesto y sus derivados podrían tener extraordinario interés farmacéutico. El modo de acción esclarecido en el TSD, reveló que se trata de una molécula de transducción de señales de proteínas kinasas 1 y 2 (MAP quinasas ERk 1 y 2) reguladas extracelularmente y activadas por mitógenos. El trisulfuro de dibencilo causó hiperfosforilación de la fosforilación de las quinasas MAP (Erk 1 y 2) inducidas mediante factor de crecimiento, un proceso crítico para el mejoramiento de la memoria a largo plazo, y que está implicado en el crecimiento neuronal. El trisulfuro de dibencilo y sus derivados mostraron una poderosa actividad citotóxica y antiproliferativa en una amplia gama de líneas celulares de cáncer. La actividad citotóxica del TSD se incrementaba de 70 á 1000 veces, cuando se vinculaba a la albúmin in vitro. El trisulfuro de dibencilo parece poseer un mecanismo conmutador citoquínico que regula por decremento las citoquinas provenientes de la vía de las células auxiliares de tipo 1 (células Th-1), que contiene varias citoquinas pro-inflamatorias y regula por incremento las de la vía de las células auxiliares de tipo 2 (Th-2). El trisulfuro regula por incremento los parámetros del sistema reticuloendotelial, p.ej. los conteos de granulocitos y el aumento tanto de las masas tímicas como de las masas de placas de Peyer, a través de los procesos de proliferación celular, de los cuales se sabe que son regulados mediante la vía de la transducción de señales de la quinasa MAP. Cuando los cigotos de Asternia pectinifera (estrella de mar) fueron expuestos al TSD a una concentración de 10 mM ­ una dosis letal para todas las células cancerosas sometidas a prueba ­ se observó que el proceso sensible de biosíntesis de la proteína no era afectado. De modo similar, la proliferación del fibroblasto humano HOFA ­ una línea celular no cancerosa ­ no fue afectada severamente por el TSD a 8.9 µM en siete días ­ una concentración letal para la mayoría de las líneas celulares cancerosas sometidas a prueba. Las implicaciones de los hallazgos se pondrán de relieve en el presente estudio


Assuntos
Humanos , Compostos de Benzil/uso terapêutico , Extratos Vegetais , Fitoterapia , Sulfetos/uso terapêutico , Antígenos CD/fisiologia , Caderinas/fisiologia , Compostos de Benzil/farmacologia , Regulação para Cima/fisiologia , Sulfetos/farmacologia , Transdução de Sinais/efeitos dos fármacos
14.
Acta bioquím. clín. latinoam ; 28(3): 425-31, sept. 1994. tab, ilus
Artigo em Espanhol | LILACS | ID: lil-141643

RESUMO

Eluciones susivas con distintos solventes del carbón activado, usado como adsorbente del Agua del Volcán Copahue (AVC) permitieron confirmar de nuevo que la extrema acidez de las muestras naturales obtenidas de la vertiente, no es la principal causa del efecto antibiótico, en contacto de breve período en las valoraciones biológicas. Los ensayos cromatográficos, aplicando reactivos microquímicos específicos y modificados, permitieron la detección de los principales compuestos acídicos, a partir de los eluidos residuales sucesivos, respectivamente obtenidos con acetato de etilo y con éter sulfúrico. Con acetato de metanólicos. Se sugiere que el AVC contiene, además de los productos sulfurosos bioactivos, otros elementos que actuarían en forma aditiva o sinérgica en los efectos biocidas y regenerativos, importantes en la crenoterapia


Assuntos
Carvão Ativado (Saúde Ambiental) , Antibiose , Argentina , Dermatopatias/terapia , Sulfetos/uso terapêutico , Algoritmos , Verde de Bromocresol , Azul de Bromofenol , Carvão Vegetal , Fenômenos Químicos , Cromatografia em Papel , Sinergismo Farmacológico , Saúde Ambiental
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