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  1 / 2056 MEDLINE  
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[PMID]:29408309
[Au] Autor:Mohamed DI; Nabih ES; El-Waseef DAA; El-Kharashi OA; Abd El Samad AA
[Ad] Endereço:Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
[Ti] Título:The protective effect of pentoxifylline versus silymarin on the pancreas through increasing adenosine by CD39 in a rat model of liver cirrhosis: Pharmacological, biochemical and histological study.
[So] Source:Gene;651:9-22, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Impaired glucose homoeostasis due to insulin resistance and decrease sensitivity of pancreatic ß-cells is a feature of liver disease and results into hepatogenous diabetes. Decrease expression of CD39 was linked to inflammation and occurrence of diabetes. Therefore, we performed this study to explore the protective effect of pentoxifylline (PTX) and silymarin administration on the ß-cells of the pancreas in a rat model of thioacetamide induced liver cirrhosis. Biochemical, histological and immunohistochemistry studies of the liver and pancreas were performed and provided an evidence on the protective effect of PTX to pancreatic ß-cells compared to silymarin. Also, silymarin induced a significant improvement of liver cirrhosis compared to PTX. In conclusion, the potential protective effect of PTX against ß-cells deterioration could be attributed to increasing pancreatic CD39 expression and the subsequent increase of adenosine.
[Mh] Termos MeSH primário: Adenosina/metabolismo
Antígenos CD/metabolismo
Apirase/metabolismo
Cirrose Hepática Experimental/tratamento farmacológico
Pâncreas/efeitos dos fármacos
Pentoxifilina/uso terapêutico
Substâncias Protetoras/uso terapêutico
Silimarina/uso terapêutico
[Mh] Termos MeSH secundário: Amilases/sangue
Animais
Modelos Animais de Doenças
Células Secretoras de Insulina/efeitos dos fármacos
Fígado/patologia
Cirrose Hepática Experimental/metabolismo
Cirrose Hepática Experimental/patologia
Testes de Função Hepática
Masculino
Pâncreas/patologia
Ratos
Ratos Wistar
Fator de Crescimento Transformador beta1/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD); 0 (Protective Agents); 0 (Silymarin); 0 (Transforming Growth Factor beta1); EC 3.2.1.- (Amylases); EC 3.6.1.5 (Apyrase); EC 3.6.1.5 (CD39 antigen); K72T3FS567 (Adenosine); SD6QCT3TSU (Pentoxifylline)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


  2 / 2056 MEDLINE  
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[PMID]:29442036
[Au] Autor:Pivodová V; Zahler S; Karas D; Valentová K; Ulrichova J
[Ti] Título: study of 2,3-dehydrosilybin and its galloyl esters as potential inhibitors of angiogenesis.
[So] Source:Pharmazie;71(8):478-483, 2016 08 01.
[Is] ISSN:0031-7144
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:2,3-Dehydrosilybin exhibits substantial anticancer and antiangiogenic effects, which can be potentially improved by semi-synthetic modification such as esterification with gallic acid. The aim of this study was to examine the potential antiangiogenic effect of 2,3-dehydrosilybin and its galloyl esters (3-O-galloyl-2,3-dehydrosilybin; 7-O-galloyl-2,3-dehydrosilybin; 20-O-galloyl-2,3-dehydrosilybin and 23-O-galloyl-2,3-dehydrosilybin) and to determine which molecular mechanism could be responsible for their activity. The effect on cell proliferation, tube formation, signal transduction pathways (PI3K/Akt and ERK) and the cell cycle was studied in human microvascular endothelial cells (HMEC). The results showed that all compounds decreased the growth of HMEC, but the strongest effect was observed for 20-O-galloyl-2,3-dehydrosilybin at 5 µmol/l. In addition, at 5 and 10 µmol/l, this was the only compound that significantly inhibited HMEC tube formation. Based on an assessment of Akt and ERK1/2 expression, we suggest that 20-O-galloyl-2,3-dehydrosilybin influences the angiogenic process through the Akt pathway.
[Mh] Termos MeSH primário: Inibidores da Angiogênese/farmacologia
Silimarina/farmacologia
[Mh] Termos MeSH secundário: Inibidores da Angiogênese/síntese química
Ciclo Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Células Endoteliais/efeitos dos fármacos
Ésteres/síntese química
Ésteres/farmacologia
Ácido Gálico/síntese química
Ácido Gálico/farmacologia
Seres Humanos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
Microtúbulos/efeitos dos fármacos
Neovascularização Patológica/tratamento farmacológico
Proteína Oncogênica v-akt/efeitos dos fármacos
Fosfatidilinositol 3-Quinases/efeitos dos fármacos
Silimarina/síntese química
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Esters); 0 (Silymarin); 4RKY41TBTF (silybin); 632XD903SP (Gallic Acid); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Oncogene Protein v-akt)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1691/ph.2016.6579


  3 / 2056 MEDLINE  
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[PMID]:29289267
[Au] Autor:Ibrahim ME; Bana EE; El-Kerdasy HI
[Ad] Endereço:Internal Medicine Department, Faculty of Medicine, Benha University, Benha, Egypt. Electronic address: tantawy_d@yahoo.com.
[Ti] Título:Role of Bone Marrow Derived Mesenchymal Stem Cells and the Protective Effect of Silymarin in Cisplatin-Induced Acute Renal Failure in Rats.
[So] Source:Am J Med Sci;355(1):76-83, 2018 Jan.
[Is] ISSN:1538-2990
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cisplatin is a highly effective antitumor agent whose clinical application is limited by its nephrotoxicity, which is associated with high mortality and morbidity rates. We aimed to study the protective role of silymarin and mesenchymal stem cells as a therapeutic tool of cisplatin nephrotoxicity. MATERIALS AND METHODS: We injected rats with cisplatin in a dose of 5mg/kg body weight for 5 days to induce acute renal failure (ARF). Silymarin was administrated 6 hours before cisplatin injection and mesenchymal stem cells were injected 24 hours after cisplatin-induced ARF. RESULTS: We assessed the ARF biochemically by elevation of kidney function tests and histopathologically by an alteration of the histological architecture of the renal cortex in the form of shrinkage of glomeruli, lobulated tufts and glomerular hypertrophy with narrowing capsular space. The tubules showed extensive tubular degeneration with cellular hyaline materials and debris in the lumen of the renal tubules. The renal blood vessels appeared sclerotic with marked thickened walls. When silymarin was given in different doses before cisplatin, it decreased the toxic effect of cisplatin in the kidney but sclerotic blood vessels remained. Injection of mesenchymal stem cells in rats with cisplatin-induced ARF improved the histopathological effects of cisplatin in renal tissues and kidney function tests were significantly improved. CONCLUSIONS: There was a significant improvement in kidney function tests and renal histopathology by using silymarin as protective mechanism in cisplatin-induced ARF. Administration of mesenchymal stem cells denoted a more remarkable therapeutic effect in ARF.
[Mh] Termos MeSH primário: Lesão Renal Aguda
Células da Medula Óssea/metabolismo
Cisplatino/efeitos adversos
Transplante de Células-Tronco Mesenquimais
Células Mesenquimais Estromais/metabolismo
Silimarina/farmacologia
[Mh] Termos MeSH secundário: Lesão Renal Aguda/induzido quimicamente
Lesão Renal Aguda/metabolismo
Lesão Renal Aguda/patologia
Lesão Renal Aguda/terapia
Aloenxertos
Animais
Células da Medula Óssea/patologia
Cisplatino/farmacologia
Modelos Animais de Doenças
Masculino
Células Mesenquimais Estromais/patologia
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Silymarin); Q20Q21Q62J (Cisplatin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180101
[St] Status:MEDLINE


  4 / 2056 MEDLINE  
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[PMID]:29342206
[Au] Autor:Papackova Z; Heczkova M; Dankova H; Sticova E; Lodererova A; Bartonova L; Poruba M; Cahova M
[Ad] Endereço:Department of Metabolism and Diabetes, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
[Ti] Título:Silymarin prevents acetaminophen-induced hepatotoxicity in mice.
[So] Source:PLoS One;13(1):e0191353, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acetaminophen or paracetamol (APAP) overdose is a common cause of liver injury. Silymarin (SLM) is a hepatoprotective agent widely used for treating liver injury of different origin. In order to evaluate the possible beneficial effects of SLM, Balb/c mice were pretreated with SLM (100 mg/kg b.wt. per os) once daily for three days. Two hours after the last SLM dose, the mice were administered APAP (300 mg/kg b.wt. i.p.) and killed 6 (T6), 12 (T12) and 24 (T24) hours later. SLM-treated mice exhibited a significant reduction in APAP-induced liver injury, assessed according to AST and ALT release and histological examination. SLM treatment significantly reduced superoxide production, as indicated by lower GSSG content, lower HO-1 induction, alleviated nitrosative stress, decreased p-JNK activation and direct measurement of mitochondrial superoxide production in vitro. SLM did not affect the APAP-induced decrease in CYP2E1 activity and expression during the first 12 hrs. Neutrophil infiltration and enhanced expression of inflammatory markers were first detected at T12 in both groups. Inflammation progressed in the APAP group at T24 but became attenuated in SLM-treated animals. Histological examination suggests that necrosis the dominant cell death pathway in APAP intoxication, which is partially preventable by SLM pretreatment. We demonstrate that SLM significantly protects against APAP-induced liver damage through the scavenger activity of SLM and the reduction of superoxide and peroxynitrite content. Neutrophil-induced damage is probably secondary to necrosis development.
[Mh] Termos MeSH primário: Acetaminofen/efeitos adversos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
Silimarina/farmacologia
[Mh] Termos MeSH secundário: Acetaminofen/farmacologia
Animais
Overdose de Drogas/patologia
Fígado/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Necrose/patologia
Substâncias Protetoras/farmacologia
Silimarina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Protective Agents); 0 (Silymarin); 362O9ITL9D (Acetaminophen)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191353


  5 / 2056 MEDLINE  
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[PMID]:29232573
[Au] Autor:Fatehi D; Mohammadi M; Shekarchi B; Shabani A; Seify M; Rostamzadeh A
[Ad] Endereço:Department of Medical Physics, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
[Ti] Título:Radioprotective effects of Silymarin on the sperm parameters of NMRI mice irradiated with γ-rays.
[So] Source:J Photochem Photobiol B;178:489-495, 2018 Jan.
[Is] ISSN:1873-2682
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Free radicals and reactive oxygen species (ROS) are generated using various endogenous systems or from external sources such as exposure to different physiochemicals. Ionizing radiation damage to the cell can be caused by the direct or indirect effects of radiotherapy processes. Silymarin (SM), a flavanolignan compound, has been identified as a natural potent antioxidant with cytoprotection activities due to scavenging free radicals. The aim of the present study was to evaluate the radioprotective effect of SM on sperm parameters of mice induced by γ-rays. A total number of 40 adult, male NMRI mice were randomly divided into four equal groups. The control group was neither treated with SM nor irradiated by γ-rays. The second group was only irradiated with 2Gy of γ-rays. The third group was firstly treated with 50mg/kg of SM for 7 consecutive days, and one day later, last injections were irradiated by 2Gy of γ-rays. The fourth groups received only 50mg/kg of SM for 7 consecutive days. All the animals were treated intraperitoneally. Histopathological and morphometrical examinations were performed. The data were analyzed using ANOVA and Tukey post hoc test. A value of p<0.05 was considered significant. The results showed that in the radiation-only group when compared with those treated with SM and irradiated, a significant different was observed in testicular parameters and DNA damage (p<0.05). In conclusion, SM can be considered as a promising herbal radioprotective agent in complementary medicine which may play an important role to protect normal spermatocytes against possible effects of γ-radiation-induced cellular damage.
[Mh] Termos MeSH primário: Raios gama
Protetores contra Radiação/farmacologia
Silimarina/farmacologia
Espermatozoides/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Dano ao DNA/efeitos dos fármacos
Dano ao DNA/efeitos da radiação
Histonas/metabolismo
Masculino
Camundongos
Protaminas/metabolismo
Protetores contra Radiação/química
Espécies Reativas de Oxigênio/metabolismo
Silimarina/química
Motilidade Espermática/efeitos dos fármacos
Motilidade Espermática/efeitos da radiação
Espermatozoides/efeitos da radiação
Testículo/efeitos dos fármacos
Testículo/fisiologia
Testículo/efeitos da radiação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Histones); 0 (Protamines); 0 (Radiation-Protective Agents); 0 (Reactive Oxygen Species); 0 (Silymarin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE


  6 / 2056 MEDLINE  
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[PMID]:29175455
[Au] Autor:Kosari-Nasab M; Shokouhi G; Ghorbanihaghjo A; Abbasi MM; Salari AA
[Ad] Endereço:Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
[Ti] Título:Anxiolytic- and antidepressant-like effects of Silymarin compared to diazepam and fluoxetine in a mouse model of mild traumatic brain injury.
[So] Source:Toxicol Appl Pharmacol;338:159-173, 2018 01 01.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Clinical and experimental studies have shown that mild traumatic brain injury (mTBI) is associated with increased anxiety- and depression-related behaviors and inflammation in the brain. Unfortunately, there are no specific therapies for long-term behavioral consequences of mTBI. This study set out to determine whether silymarin treatment compared to diazepam (DZP) and fluoxetine (FLX) can reduce neuroinflammation, anxiety- and depression-like behaviors after mTBI induction in mice. We used open field, elevated plus maze, light-dark box, zero maze, sucrose preference, forced swim, and tail suspension tests to assess anxiety and depression-like behaviors in mTBI-induced mice. The levels of tumor necrosis factor (TNF)-α protein, a marker of inflammation, in the prefrontal cortex and hippocampus was also measured. This study identified that the long-term treatment with DZP, FLX or SIL results in decreased anxiety and depression-like behaviors in mTBI-induced mice. The results also showed that these drugs reduced TNF-α levels in the prefrontal cortex and hippocampus. In addition, there were no significant differences between the effects of SIL and DZP or SIL and FLX on behavioral and cytokine levels in mTBI-induced mice. Our findings support the idea that mTBI could be a risk factor for anxiety- and depression-related disorders and neuroinflammation in the brain. Taken together, this study demonstrates that DZP, FLX or SIL can significantly reduce anxiety- and depression-like symptoms, and neuroinflammation after mTBI induction in mice.
[Mh] Termos MeSH primário: Ansiolíticos/farmacologia
Antidepressivos/farmacologia
Lesões Encefálicas Traumáticas/psicologia
Diazepam/farmacologia
Fluoxetina/farmacologia
Silimarina/farmacologia
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Aprendizagem em Labirinto/efeitos dos fármacos
Camundongos
Fator de Necrose Tumoral alfa/análise
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Anxiety Agents); 0 (Antidepressive Agents); 0 (Silymarin); 0 (Tumor Necrosis Factor-alpha); 01K63SUP8D (Fluoxetine); Q3JTX2Q7TU (Diazepam)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


  7 / 2056 MEDLINE  
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[PMID]:29309065
[Au] Autor:Colica C; Boccuto L; Abenavoli L
[Ad] Endereço:CNR, IBFM UOS of Germaneto, University "Magna Graecia", Catanzaro 88100, Italy.
[Ti] Título:Silymarin: An option to treat non-alcoholic fatty liver disease.
[So] Source:World J Gastroenterol;23(47):8437-8438, 2017 Dec 21.
[Is] ISSN:2219-2840
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We have read with a great interest the review published by Singh et al, on the treatment options in alcoholic and non-alcoholic fatty liver disease, including various new targeted therapies that are currently under investigation. Recently, we described the health effects of the Mediterranean diet associated to an antioxidant complex rich in silymarin, to improve in overweight patients anthropometric parameters, glucose and lipid metabolism and intra-hepatic fat accumulation.
[Mh] Termos MeSH primário: Hepatopatia Gordurosa não Alcoólica
Silimarina
[Mh] Termos MeSH secundário: Antioxidantes
Seres Humanos
Metabolismo dos Lipídeos
Sobrepeso
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Antioxidants); 0 (Silymarin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180110
[Lr] Data última revisão:
180110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE
[do] DOI:10.3748/wjg.v23.i47.8437


  8 / 2056 MEDLINE  
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[PMID]:29245314
[Au] Autor:Zhong S; Fan Y; Yan Q; Fan X; Wu B; Han Y; Zhang Y; Chen Y; Zhang H; Niu J
[Ad] Endereço:aDepartment of Neurosurgery, The First Hospital of Jilin UniversitybClinical College, Jilin UniversitycHepatopancreatobiliary Medicine Department, The First Hospital of Jilin University, ChangchundBasic Medical College, Qiqihar Medical University, QiqihareDepartment of Radiology, The First Hospital of Jilin University, Changchun, China.
[Ti] Título:The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease: A meta-analysis (PRISMA) of randomized control trials.
[So] Source:Medicine (Baltimore);96(49):e9061, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Silymarin (SIL) is an active extraction of the silybum marianum, milk thistle, which is an ancient medicinal plant for treatment of various liver diseases for centuries. This study is to assess the therapeutic effect of SIL in the treatment of nonalcoholic fatty liver disease through meta-analysis. METHODS: Published randomized controlled trials (RCTs) were included from electronic databases (PubMed, Embase, Cochrane library, Web of Science, and so forth). Cochrane handbook was applied to evaluate the methodological quality. All statistical analyses were directed by Revman 5.3 software, and statistical significance was defined as P < .05. RESULTS: Eight RCTs involved 587 patients were included in this study. The results showed that SIL reduced the AST and ALT levels more significantly than the control group (AST UI/L: MD = -6.57; 95% CI, -10.03 to -3.12; P = .0002; ALT UI/L: MD = -9.16; 95% CI, -16.24 to -2.08; P = .01). Compared with other interventions, there were significant differences decreasing AST and ALT levels when SIL was used alone (AST UI/L: MD = -5.44; 95% CI, -8.80 to -2.08; P = .002; ALT UI/L: MD = -5.08; 95% CI, -7.85 to -2.32; P = .0003). CONCLUSION: SIL has positive efficacy to reduce transaminases levels in NAFLD patients. SIL can be an encouraging and considerable phytotherapy for NAFLD patients.
[Mh] Termos MeSH primário: Antioxidantes/uso terapêutico
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico
Fitoterapia/métodos
Silimarina/uso terapêutico
[Mh] Termos MeSH secundário: Seres Humanos
Testes de Função Hepática
Ensaios Clínicos Controlados Aleatórios como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Antioxidants); 0 (Silymarin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171217
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009061


  9 / 2056 MEDLINE  
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[PMID]:28454924
[Au] Autor:Marcolino Assis-Júnior E; Melo AT; Pereira VBM; Wong DVT; Sousa NRP; Oliveira CMG; Malveira LRC; Moreira LS; Souza MHLP; Almeida PRC; Lima-Júnior RCP
[Ad] Endereço:Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Brazil.
[Ti] Título:Dual effect of silymarin on experimental non-alcoholic steatohepatitis induced by irinotecan.
[So] Source:Toxicol Appl Pharmacol;327:71-79, 2017 07 15.
[Is] ISSN:1096-0333
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Irinotecan-based regimens are commonly used for treatment of colorectal cancer, which is limited by mucositis and non-alcoholic steatohepatitis (NASH). Silymarin (SIL) prevents fatty liver disease in the clinical setting and in models of liver damage induced chemically. This study investigated the possible effect of SIL on irinotecan (IRI)-induced NASH. Swiss female mice were injected with saline (SAL 5ml/kg i.p.), IRI (50mg/kg i.p.), SIL (150mg/kg p.o.) or IRI (50mg/kg i.p.)+(SIL 1.5, 15 or 150mg/kg p.o.) thrice/week/7weeks. On the seventh week, blood samples were collected for transaminases assay and livers were collected for histopathology, measurement of the total lipids, malondyadehyde (MDA), non-protein sulfhydryl groups (NPSH), cytokines (IL-1ß, IL 6 and IL-10), 3-nitrotyrosine (N-Tyr) and toll-like receptor 4 (TLR4) immunoexpression, quantification of NF-kB, α-smooth muscle actin (α-SMA), and Escherichia coli 16S rRNA gene (RRS) expression. IRI increased liver transaminases, neutrophil infiltration, lipid accumulation, MDA, IL-1ß and IL-6 levels, N-Tyr and TLR4 immunostaining, NF-kB, α-SMA expression and RRS versus the SAL group (p<0.05). Additionally, SIL (1.5mg/kg) improved these parameters (p<0.05), except neutrophil infiltration and RSS versus the IRI group. Furthermore, the SIL (15mg/kg) only improved the inflammatory parameters, the expression of α-SMA and RRS versus the IRI group (p<0.05). The higher dose of SIL (150mg/kg) was even more deleterious than the intermediate dose. Therefore, silymarin showed a dual effect on liver damage induced by IRI. Hepatoprotection seems to involve the inhibition of oxidative stress and protein nitrosylation, preventing activation of hepatic fibrosis mechanisms.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/uso terapêutico
Antineoplásicos Fitogênicos/toxicidade
Camptotecina/análogos & derivados
Hepatopatia Gordurosa não Alcoólica/induzido quimicamente
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico
Silimarina/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Infecções Bacterianas/tratamento farmacológico
Infecções Bacterianas/patologia
Biomarcadores/metabolismo
Camptotecina/toxicidade
Citocinas/metabolismo
Feminino
Metabolismo dos Lipídeos/efeitos dos fármacos
Fígado/microbiologia
Fígado/patologia
Testes de Função Hepática
Camundongos
Infiltração de Neutrófilos
Hepatopatia Gordurosa não Alcoólica/patologia
Estresse Oxidativo/efeitos dos fármacos
Compostos de Sulfidrila/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Antineoplastic Agents, Phytogenic); 0 (Biomarkers); 0 (Cytokines); 0 (Silymarin); 0 (Sulfhydryl Compounds); 7673326042 (irinotecan); XT3Z54Z28A (Camptothecin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:28458011
[Au] Autor:Gülden M; Appel D; Syska M; Uecker S; Wages F; Seibert H
[Ad] Endereço:Institute of Toxicology and Pharmacology for Natural Scientists, University Medical School Schleswig-Holstein, Campus Kiel, Brunswiker Str. 10, 24105 Kiel, Germany. Electronic address: michael.guelden@t-online.de.
[Ti] Título:Chrysin and silibinin sensitize human glioblastoma cells for arsenic trioxide.
[So] Source:Food Chem Toxicol;105:486-497, 2017 Jul.
[Is] ISSN:1873-6351
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Arsenic trioxide (ATO) is highly efficient in treating acute promyelocytic leukemia. Other malignancies, however, are often less sensitive. Searching for compounds sensitizing arsenic resistant tumours for ATO the plant polyphenols, chrysin and silibinin, and the ATP binding cassette (ABC) transporter inhibitor MK-571, respectively, were investigated in human glioblastoma A-172 cells. The sensitivity of A-172 cells to ATO was characterized by a median cytotoxic concentration of 6 µM ATO. Subcytotoxic concentrations of chrysin, silibinin and MK-571, respectively, remarkably increased the sensitivity of the cells to ATO by factors of 4-6. Isobolographic analysis revealed synergistic interaction of the polyphenols and MK-571, respectively, with ATO. Sensitization by chrysin was associated with depletion of cellular glutathione and increased accumulation of arsenic. In contrast, silibinin and also MK-571 increased the accumulation of arsenic more strongly but without affecting the glutathione level. The increase of arsenic accumulation could be attributed to a decreased rate of arsenic export and, additionally, in the case of silibinin and MK-571, to an increasing amount of irreversibly accumulated arsenic. Direct interaction with ABC transporters stimulating export of glutathione and inhibiting export of arsenic, respectively, are discussed as likely mechanisms of the sensitizing activity of chrysin and silibinin.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Flavonoides/farmacologia
Glioblastoma/tratamento farmacológico
Óxidos/toxicidade
Silimarina/farmacologia
[Mh] Termos MeSH secundário: Transportadores de Cassetes de Ligação de ATP/genética
Transportadores de Cassetes de Ligação de ATP/metabolismo
Apoptose/efeitos dos fármacos
Arsenicais
Linhagem Celular Tumoral
Glioblastoma/genética
Glioblastoma/metabolismo
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATP-Binding Cassette Transporters); 0 (Antineoplastic Agents); 0 (Arsenicals); 0 (Flavonoids); 0 (Oxides); 0 (Silymarin); 3CN01F5ZJ5 (chrysin); 4RKY41TBTF (silybin); S7V92P67HO (arsenic trioxide)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171213
[Lr] Data última revisão:
171213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE



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