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2.
Chem Biol Interact ; 314: 108815, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499054

RESUMO

Diabetic nephropathy (DN) is the one of the leading causes of end-stage renal disease (ESRD) in clinical. However, it is still lack of accurate biomarkers and effective methods for diagnosing and curing DN. Therefore, there is an urgent need to develop a definite strategy for the identification of reliable and versatile biomarkers for risk assessment of DN and search for therapeutic approaches that can effectively attenuate DN progression. Treatment with Gandi capsule (GDC) not only decreased the levels of urinary albumin excretion, but also increased the levels of estimated glomerular filtration rate (eGFR), indicating that it produces a renal protective effect on diabetic nephropathy. Based on metabolomics investigation including UHPLC-MS analysis and multivariate statistical analysis, sixteen disordered metabolites were screened out and considered as potential biomarkers corresponding to DN, which were mostly improved and partially returned to normalcy in GDC treatment group. Therefore, it was suggested that GDC was a promising therapeutic agent against DN. The underlying mechanisms of GDC attenuating the development of DN may be improving abnormal metabolic disorders by retrieving the imbalance of glycine metabolism, tryptophan metabolism, valine, leucine and isoleucine degradation, purine metabolism, nitrotoluene degradation, phenylalanine metabolism, fatty acid metabolism, tyrosine metabolism and bile acid metabolism pathways. The data obtained in this study may provide key clues to enhance our understanding of the metabolic mechanism of DN and shed new insights into the therapeutic mechanism of GDC.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Metabolômica , Substâncias Protetoras/uso terapêutico , Idoso , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Análise Discriminante , Feminino , Taxa de Filtração Glomerular , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Substâncias Protetoras/química
3.
Chemotherapy ; 64(2): 105-109, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31390619

RESUMO

BACKGROUND: Dexrazoxane (DEX) is indicated as a cardioprotective agent for breast cancer patients receiving the anthracycline doxorubicin. Two meta-analyses in metastatic breast cancer reported an apparent increase in the severity of myelosuppression when DEX was used. So far, no data in soft-tissue sarcoma (STS) patients are available. METHODS: We retrospectively analyzed hematological toxicity data from 133 consecutive STS patients who received a chemotherapy regimen containing an anthracycline and ifosfamide (AI) in the perioperative or metastatic settings between January 2006 and December 2017. Of these, 46 received off-label DEX concurrently with the AI treatment. The differences between incidence of any of the explored outcomes were assessed according to the Fisher exact test. RESULTS: Compared with the non-DEX group, DEX treatment was associated with significantly higher rates of grade 3/4 hematological toxicities: leukopenia (56.5 vs. 28.7%; p = 0.0014), neutropenia (69.6 vs. 24.1%; p = 0.0001), febrile neutropenia (52.2 vs. 20.7%; p = 0.0004), anemia (41.3 vs. 28.7%; p = 0.1758), and thrombocytopenia (54.3 vs. 32.1%; p = 0.0159). Similarly, in the DEX group dose reductions were more frequent compared to the non-DEX group (39.1 vs. 19.5%; p = 0.0221). CONCLUSION: Adding DEX to AI in STS patients leads to higher rates of bone marrow suppression in all blood components, as well as to more frequent events of febrile neutropenia and dose reductions.


Assuntos
Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Dexrazoxano/uso terapêutico , Substâncias Protetoras/uso terapêutico , Sarcoma/tratamento farmacológico , Adulto , Idoso , Antraciclinas/efeitos adversos , Antibióticos Antineoplásicos/efeitos adversos , Feminino , Doenças Hematológicas/etiologia , Doenças Hematológicas/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Neutropenia/prevenção & controle , Estudos Retrospectivos , Sarcoma/patologia , Adulto Jovem
4.
An Acad Bras Cienc ; 91(3): e20180646, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31411259

RESUMO

The hepatoprotective effects of the ethanolic extracts of propolis (EEP) on alcohol-induced liver steatosis were investigated in Wistar rats. Chronic alcoholic fatty liver was induced by administration of 52% alcohol to male Wistar rats at the dose of 1% body weight for 7 weeks. Then animals were simultaneously treated with 50% ethanol solutions of EEP or normal saline at the dose of 0.1% body weight for 4 further weeks. Serological analyses and liver histopathology studies were performed to investigate the development of steatosis. Microarray analysis was conducted to investigate the alterations of hepatic gene expression profiling. Our results showed that 4-week treatment of EEP helped to restore the levels of various blood indices, liver function enzymes and the histopathology of liver tissue to normal levels. Results from the microarray analysis revealed that the hepatic expressions of genes involved in lipogenesis were significantly down-regulated by EEP treatment, while the transcriptional expressions of functional genes participating in fatty acids oxidation were markedly increased. The ability of EEP to reduce the negative effects of alcohol on liver makes propolis a potential natural product for the alternative treatment of alcoholic fatty liver.


Assuntos
Fígado Gorduroso Alcoólico/metabolismo , Hepatopatias Alcoólicas/metabolismo , Extratos Vegetais/metabolismo , Própole/metabolismo , Substâncias Protetoras/metabolismo , Alanina Transaminase/metabolismo , Animais , Apiterapia/métodos , Aspartato Aminotransferases/metabolismo , Colesterol/metabolismo , Modelos Animais de Doenças , Etanol , Ácidos Graxos/biossíntese , Fígado Gorduroso Alcoólico/tratamento farmacológico , Fígado Gorduroso Alcoólico/genética , Fígado Gorduroso Alcoólico/patologia , Hepatopatias Alcoólicas/tratamento farmacológico , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/patologia , Masculino , Oxirredução , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Própole/química , Própole/uso terapêutico , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Ratos Wistar , Análise Serial de Tecidos/métodos , Transcrição Genética/genética , Triglicerídeos/metabolismo
5.
Braz J Cardiovasc Surg ; 34(3): 271-278, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31310464

RESUMO

OBJECTIVE: The goal of the present study was to compare the myocardial protection obtained with histidine-tryptophan-ketoglutarate (HTK) cardioplegic solution (Custodiol®) and with intermittent hypothermic blood solution. METHODS: Two homogenous groups of 25 children with acyanotic congenital heart disease who underwent total correction with mean aortic clamping time of 60 minutes were evaluated in this randomized study. Troponin and creatine kinase-MB curves, vasoactive-inotropic score, and left ventricular function were obtained by echocardiogram in each group. The values were correlated and presented through graphs and tables after adequate statistical treatment. RESULTS: It was observed that values of all the studied variables varied over time, but there was no difference between the groups. CONCLUSION: We conclude that in patients with acyanotic congenital cardiopathies submitted to total surgical correction, mean aortic clamping time around one hour, and cardiopulmonary bypass with moderate hypothermia, the HTK crystalloid cardioplegic solution offers the same myocardial protection as the cold-blood hyperkalemic cardioplegic solution analyzed, according to the variables considered in our study model.


Assuntos
Soluções Cardioplégicas/uso terapêutico , Cardiopatias Congênitas/cirurgia , Análise de Variância , Creatina Quinase Forma MB/análise , Método Duplo-Cego , Ecocardiografia , Feminino , Glucose/uso terapêutico , Cardiopatias Congênitas/fisiopatologia , Humanos , Lactente , Recém-Nascido , Masculino , Manitol/uso terapêutico , Duração da Cirurgia , Cloreto de Potássio/uso terapêutico , Procaína/uso terapêutico , Estudos Prospectivos , Substâncias Protetoras/uso terapêutico , Valores de Referência , Reprodutibilidade dos Testes , Estatísticas não Paramétricas , Fatores de Tempo , Resultado do Tratamento , Troponina/análise , Função Ventricular Esquerda
6.
Khirurgiia (Mosk) ; (6): 73-79, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31317944

RESUMO

The purpose of the study is to establish the effectiveness of remaxol in the correction of endogenous intoxication in patients with acute peritonitis. MATERIAL AND METHODS: The work is based on the results of clinical and laboratory studies. The clinic examined 55 patients with acute moderate peritonitis as complication of various diseases (acute appendicitis, perforated gastric or duodenal ulcer, acute intestinal obstruction, acute destructive cholecystitis). Before surgical operation and in the early postoperative period we evaluated the severity of endogenous intoxication by the level of hydrophilic and hydrophobic toxic products. The content of molecular products of lipids peroxidation - oxidative stress, phospholipase activity were determined in the blood plasma. In the study group (n = 28) in the postoperative therapy additionally included remaxol (400 ml intravenous fluids). RESULTS: Research established that the occurrence of endogenous intoxication syndrome in patients with acute peritonitis associated with the activation of oxidative stress and phospholipases, high intensity of which is maintained even after elimination of the source of peritonitis with manifestation on the 1st day after surgery. Remaxol include leads to a significant reduction in the severity of intoxication syndrome in patients with acute peritonitis. Positive effect of the drug on the correction of endogenous intoxication is largely determined by its ability to significantly reduce oxidative stress and the activity of phospholipases, as the most important membrane destabilizing agents. The greatest detoxication effect of the drug is recorded when it is applied already at the preoperative stage of patients when its ability to reduce the activity of trigger agents of catabolic processes implemented to the greatest extent. CONCLUSION: In acute moderate peritonitis, remaxol use before surgery or in the early postoperative period in complex therapy leads to a significant correction of factors contributing to the development and preservation of the intensification of catabolic processes - one of the sources of endogenous intoxication.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Peritonite/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Succinatos/uso terapêutico , Doença Aguda , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Metabolismo/efeitos dos fármacos , Metabolismo/fisiologia , Estresse Oxidativo/fisiologia , Peritonite/etiologia , Peritonite/metabolismo , Peritonite/cirurgia , Substâncias Protetoras/farmacologia , Succinatos/farmacologia
7.
Chem Biol Interact ; 311: 108749, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31325423

RESUMO

PURPOSE: Excessive proliferation, migration and anti-apoptosis of pulmonary artery smooth muscle cells (PASMCs) are the basis for the development of pulmonary vascular remodeling, and it is the driving force for pulmonary arterial hypertension (PAH). 18ß-glycyrrhetinic acid (18ß-GA) is the main active substance extracted from Chinese herbal medicine licorice, with outstanding anti-inflammatory, anti-oxidation and anti-proliferative effects. Our team found in previous studies that 18ß-GA has protective effects on monocrotaline-induced PAH in rats. However, the anti-angiogenic effect of 18ß-GA on PAH remains unclear. Therefore, in order to further investigate whether the beneficial effects of 18ß-GA on PAH are related to its antiproliferative effect, we conducted experiments in vivo and in vitro. METHODS AND RESULTS: In vivo, 18ß-GA relieved mean pulmonary arterial pressure, right ventricular systolic pressure, and right ventricular hypertrophy index, improving pulmonary remodeling. In vitro, 18ß-GA significantly inhibited PDGF-BB-induced proliferation and DNA synthesis of HPASMCs, blocking the progression of G0/G1 to S phase of the cell cycle. Furthermore, after treatment with 18ß-GA, the expression of Rho A, ROCK1, ROCK2 was decreased and ROCK activity was inhibited in HPASMC. In addition, 18ß-GA also attenuated PDGF-induced changes in p27kip1, Bax and Bcl-2. CONCLUSIONS: In summary, these results indicate that 18ß-GA regulates the activity of RhoA-ROCK signaling pathway, inhibits the proliferation of HPASMCs, and has potential value in the treatment of PAH.


Assuntos
Ácido Glicirretínico/análogos & derivados , Hipertensão Pulmonar/patologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glicirretínico/farmacologia , Ácido Glicirretínico/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Masculino , Monocrotalina/toxicidade , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Substâncias Protetoras/uso terapêutico , Proteína Fosfatase 1/genética , Proteína Fosfatase 1/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Remodelação Vascular/efeitos dos fármacos , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismo
8.
Int J Nanomedicine ; 14: 3967-3982, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239666

RESUMO

Background: The combination of chemotherapy with radiotherapy serves as a common therapeutic strategy in clinics. However, it is unsatisfactory due to its poor therapeutic efficiency and severe side-effects originating from chemotherapy-exerted systemic toxicity as well as radiation-induced injury. Purpose: Hence, Berberine (Ber), an isoquinolin alkaloid with low toxicity and protective effects against radiotherapy, was used as a novel chemotherapeutic agent for chemo-radiotherapy of liver cancer. Patients and methods: We preloaded Ber into folic acid targeting Janus gold mesoporous silica nanocarriers (FA-JGMSNs) for overcoming the poor bioavailability of Ber. Furthermore, FA-JGMSNs were not only employed as radiosensitizers for expanding radiotherapeutic effect, but also used as photothermal agents for supplementing chemo-radiotherapeutic effect by local photothermal therapy. Results: In vitro and in vivo experiemtal results demonstrated the highly efficient anti-tumor effect, good biosafety as well as the effective protection of normal tissue of this nanoplatform. Conclusion: Based on its superb performance, we believe our work provided a feasible strategy for triple-therapies of liver cancer.


Assuntos
Berberina/uso terapêutico , Ouro/química , Hipertermia Induzida , Neoplasias Hepáticas/terapia , Nanopartículas/química , Fototerapia , Lesões por Radiação/prevenção & controle , Dióxido de Silício/química , Animais , Berberina/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Camundongos Nus , Nanopartículas/ultraestrutura , Tamanho da Partícula , Porosidade , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Lesões por Radiação/terapia , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Temperatura Ambiente
9.
An Acad Bras Cienc ; 91(2): e20181044, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31241706

RESUMO

Myristica fragrans seeds are traditionally used to treat dyspepsia, vomiting and abdominal pain. The purpose of this study was to investigate the protective effect of Myristica fragrans in ethanol induced gastric ulcer. Study was carried out on rats, divided into four groups; negative control, positive control, standard drug control, and Myristica fragrans extract treated rats. The pH, ulcer index, acidity values and histopathological examination of stomach were evaluated. Myristica fragrans significantly (P<0.05) reduced gastric lesions by 41.68% in ethanol induced ulcer model at 200 mg/kg when compared to sucralfate (60.41%). However, histopathological findings appeared similar in Myristica fragrans extract treated and standard drug control groups, where stomachs were found with mild erosion of superficial epithelium and few infiltrated inflammatory cells. pH of gastric contents of rats from extract treated was increased (4.25 ± 0.25) as compared to positive control group (2.25 ± 0.25). Ulcer index of extract treated rats was improved (41.74%). Moreover, total acidity of extract treated group (60.0 ± 0.47) was decreased as compared to control group (74.50 ± 1.04). It is concluded that Myristica fragrans showed significant protecting activity in ethanol induced ulcer. Isolation and purification of phytochemicals responsible for gastroprotective activity becomes necessary.


Assuntos
Antiulcerosos/uso terapêutico , Myristica/química , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Úlcera Gástrica/tratamento farmacológico , Animais , Antiulcerosos/isolamento & purificação , Modelos Animais de Doenças , Etanol , Masculino , Extratos Vegetais/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Ratos , Ratos Wistar , Sementes , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia
10.
An Acad Bras Cienc ; 91(2): e20181257, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31241707

RESUMO

Triptolide, a purified diterpenoid from the herb Tripterygium wilfordii Hook.f., was widely used to treat many diseases. However, the hepatotoxicity of triptolide limited its clinical use. Research showed oxidative stress played an important role in triptolide-induced liver injury. To investigate the effect of vitamin C, which was one of the most effective antioxidants, on triptolide-induced hepatotoxicity and its potential mechanism in mice. In the present study, acute liver injury was induced by intraperitoneal injection of triptolide and vitamin C was orally administered. The results showed treatment with vitamin C prevented the triptolide-induced liver injury by reducing the levels of aspartate transaminase from 286.86 to 192.48 U/mL and alanine aminotransferase from 746.75 to 203.36 U/mL. Histopathological changes of liver corresponded to the same trend. Furthermore, vitamin C also protected the liver against triptolide-induced oxidative stress by inhibiting the generation of malondialdehyde (2.22 to 1.49 nmol/mgprot) and hydrogen peroxide (14.74 to 7.19 mmol/gprot) and restoring the level of total superoxide dismutase (24.32 to 42.55 U/mgprot) and glutathione (7.69 to 13.03 µg/mgprot). These results indicated that vitamin C could protect against triptolide-induced liver injury via reducing oxidative stress, and vitamin C may pose a significant health protection in the clinical use of triptolide.


Assuntos
Ácido Ascórbico/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Diterpenos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fenantrenos/toxicidade , Substâncias Protetoras/uso terapêutico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Compostos de Epóxi/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Substâncias Protetoras/isolamento & purificação
11.
Food Chem Toxicol ; 131: 110562, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31181236

RESUMO

Brown seaweed Sargassum confusum (C. Agardh) has been used in traditional Chinese medicine to treat a variety of diseases. The aim of the present study was to evaluate the anti-diabetic effect of oligosaccharides from brown seaweed S. confusum (SCO). The anti-diabetic effect of SCO was evaluated in vivo using high-fat/high-sucrose fed hamsters. Molecular mechanisms of modulating gene expression of specific members of insulin signaling pathways were determined. The components of the intestinal microflora in diabetic animals were also analyzed by high-throughput 16S rRNA gene sequencing. And it was found that SCO had a sequence of sulfated anhydrogalactose and methyl sulfated galactoside units. Fasting blood glucose levels were significantly decreased after SCO administration. Histology showed that SCO could protect the cellular architecture of the liver. SCO could also significantly increase the relative abundance of Lactobacillus and Clostridium XIVa and decrease that of Allobaculum, Bacteroides and Clostridium IV. The active role of SCO in anti-diabetic effect was revealed by its regulation of insulin receptor substrate 1/phosphatidylinositol 3-kinase and c-Jun N-terminal kinase pathways. These results suggested that SCO might be used as a functional material to regulate gut microbiota in obese and diabetic individuals.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Oligossacarídeos/uso terapêutico , Sargassum/química , Animais , Bactérias/genética , Sequência de Bases , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Dieta da Carga de Carboidratos , Dieta Hiperlipídica , Hipoglicemiantes/isolamento & purificação , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Mesocricetus , Oligossacarídeos/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/uso terapêutico , RNA Ribossômico 16S/genética , Alga Marinha/química
12.
Food Chem Toxicol ; 131: 110579, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202940

RESUMO

Disintegration of the intestine caused by deoxynivalenol (DON), which is a fungal metabolite found in cereal grain-based human and animal diets, triggers severe intestinal inflammatory disease. Hydrolyzed wheat gluten (HWG) can promote the development of intestine. Therefore, HWG was administered orally to male mice on 1-14 days, and DON was administered to them on 4-11 days. Feed, water intake and body weight were recorded all over the experimental period. Blood samples were collected then the mice were sacrificed to collect the jejunum for crypt isolation and culture. The intestinal morphology was observed by electron microscopy, and Western blotting was used to investigate intestinal stem cell (ISC) proliferation and differentiation, as well as the primary regulatory mechanism of the Wnt/ß-catenin signaling. The results showed that HWG increased the average daily gain and average daily water intake of mice under DON-induced injury conditions, and increased the jejunum weight, villous height in the jejunum, and promoted jejunal crypt cell expansion. The DON-induced decrease in Wnt/ß-catenin activity, the expression of Ki67, PCNA and KRT20 were rescued by HWG in the jejunum, crypt and enteroid, as well as the number of goblet cells and Paneth cells. Furthermore, HWG increased jejunum diamine oxidase (DAO) activity. In conclusion, HWG alleviates DON-induced intestinal injury by enhancing ISC proliferation and differentiation in a Wnt/ß-catenin-dependent manner.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glutens/uso terapêutico , Enteropatias/prevenção & controle , Células-Tronco/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Fármacos Gastrointestinais/química , Fármacos Gastrointestinais/uso terapêutico , Glutens/química , Hidrólise , Enteropatias/induzido quimicamente , Jejuno/citologia , Jejuno/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Tricotecenos , Triticum/química , Proteínas Wnt/metabolismo , beta Catenina/metabolismo
13.
Food Chem Toxicol ; 131: 110591, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31212009

RESUMO

Kidney ischemia reperfusion injury (IRI) is an acute kidney injury associated with high number of mortality. We have examined the molecular mechanism and found that oxidative stress and hypoxia leads to induction of autophagy. In IRI induced autophagy, TFEB translocated to nucleus in response to IRI and induced a number of target genes of Coordinated Lysosomal Expression and Regulation (CLEAR) network. Real-time PCR analyses result showed IRI dependent increase in mRNA level to lysosomal hydrolases (Ctsa, Psap), lysosomal membranes (Lamp1), lysosomal acidification (Atp6ap1) non-lysosomal proteins involved in lysosomal biogenesis (M6pr, Nagpa) and autophagy (Becn1, VPS11). Overall, both lysosomal biogenesis and autophagy pathways were induced. Two key players of TFEB dependent proteins in autophagy, LAMP1 and BECN1 were verified by protein analyses. Pretreatment with urolithin A promoted autophagy and attenuated renal injury in kidney IRI and thus inverse relationship existed between TFEB-CLEAR pathway and kidney injury. Urolithin A also attenuated IRI induced pro-inflammatory cytokines TNFα, IL1ß, MIP1α and MIP2 mRNA and associated kidney injury. Overall, our results explored the understanding of autophagy and CLEAR network to kidney IRI and those insights may help to develop new therapeutic strategies to protect against IRI.


Assuntos
Lesão Renal Aguda/prevenção & controle , Autofagia/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Cumarínicos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Lesão Renal Aguda/fisiopatologia , Animais , Autofagia/fisiologia , Núcleo Celular/metabolismo , Citocinas/metabolismo , Inflamação/prevenção & controle , Rim/patologia , Rim/fisiopatologia , Lisossomos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Traumatismo por Reperfusão/fisiopatologia
14.
Food Chem Toxicol ; 131: 110582, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31220535

RESUMO

Alcoholism is a serious addiction that can lead to various health complications such as liver fibrosis, steatosis, and cirrhosis. Carvacrol is present in many plant-based essential oils and used as a preservative in the food industry. In this study, we have investigated the hepatoprotective role of carvacrol against ethanol-induced liver toxicity in mice. To determine the effect of carvacrol on liver injury parameters, 5 doses of 50% ethanol (10 mL/kg body weight) were orally administered every 12 h for inducing the hepatotoxicity in experimental mice. Interestingly, carvacrol pre-treatment (50 and 100 mg/kg) reversed the ethanol-induced effects on liver function, antioxidant markers, matrix metalloproteinases activities, and histological changes. Moreover, carvacrol binds to the active pocket of cytochrome P450 (Cyt P450) and inhibits its expression. Thus, our finding suggests carvacrol can be used as an adjuvant for the amelioration of alcohol-induced hepatotoxicity.


Assuntos
Inibidores das Enzimas do Citocromo P-450/uso terapêutico , Fígado Gorduroso Alcoólico/prevenção & controle , Monoterpenos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Autofagia/efeitos dos fármacos , Bebedeira , Domínio Catalítico , Inibidores das Enzimas do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Fígado Gorduroso Alcoólico/patologia , Fígado/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos ICR , Simulação de Acoplamento Molecular , Monoterpenos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/metabolismo , Ligação Proteica
15.
Life Sci ; 228: 305-315, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31047898

RESUMO

Silymarin, an extract from Silybum marianum (milk thistle) containing a standardized mixture of flavonolignans that ameliorates some types of liver disease and, more recently, kidney damage, could be used for the ROS-scavenging effect of these antioxidants. Furthermore, contrast-induced nephropathy (CIN) is an iatrogenic impairment of renal function in patients subjected to angiographic procedures for which there is not yet a successful preventative treatment. Recent evidence has shown that this event is related to tubular/vascular injury activated mainly by oxidative stress. However, whether this bioavailable and pharmacologically safe extract protects against CIN is not clear. We proposed to evaluate the possible protective role of the antioxidant silymarin in an experimental model of CIN. Adult male Swiss mice were separated into 6 groups and pretreated orally with silymarin (50, 200 and 300 mg/kg), N-acetylcysteine (200 mg/kg) or vehicle for 5 days before the CIN and control groups. Renal function was analyzed by plasma creatinine, urea and cystatin C levels. Additionally, blood reactive oxygen species (ROS) were evaluated using ROS bioavailability, protein oxidation and DNA damage. Renal oxidative damage was evaluated using apoptosis/cell viability assays and histological analysis. We showed that silymarin preserved renal function and decreased systemic and renal oxidative damage (antigenotoxic and antiapoptotic properties, respectively) in a dose-dependent manner and was superior to conventional treatment with N-acetylcysteine. Histologically, silymarin treatment also had beneficial effects on renal glomerular and tubular injuries. Therefore, silymarin prophylaxis may be an interesting strategy for the prevention of CIN.


Assuntos
Meios de Contraste/efeitos adversos , Rim/efeitos dos fármacos , Nefrite/induzido quimicamente , Nefrite/prevenção & controle , Substâncias Protetoras/uso terapêutico , Silimarina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Cardo Mariano/química , Nefrite/metabolismo , Nefrite/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/química , Silimarina/química
16.
Gene ; 708: 14-20, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31082504

RESUMO

INTRODUCTION: Renal ischemia/reperfusion injury (IRI) remains one of the most diseases in clinic. The purpose of this study was to investigate the potential role and mechanism of propofol in protecting mice kidney from IRI. METHODS: Renal I/R model was established in C57/BL6 mice by clamping bilateral renal pedicles for 35 min. The mice were randomly divided into four groups: sham group, IR group, IR + Propofol group, and IR + Propofol+LY294002 group. Histological assessment of kidney was conducted by HE staining and the levels of serum creatinine (SCr) and blood urea nitrogen (BUN) of each group were measured. Expressions of inflammatory factors (IL-6, TNF-α) were detected by qRT-PCR and immunoblotting. The expression levels of cleaved Caspasse-3, PI3K, Akt, p-Akt, mTOR, and p-mTOR within renal tissue samples were measured by Western Blot. RESULTS: The levels BUN, Cr and morphological damage score increased significantly after renal IRI. However, such changes could be prevented by propofol. Besides, IRI reduced renal expressions of PI3K, p-Akt, p-mTOR, and increased the levels of IL-6, TNF-α,cl-caspase-3 in kidney, After propofol treatment, these changes were significantly alleviated, but the use of PI3K inhibitor LY294002 could reverse the effects of propofol. CONCLUSION: Propofol can protect renal IRI partially by reducing apoptosis and release of inflammatory cytokines, which is possibly involved in the modulation of the PI3K/AKT/mTOR signaling pathway. Our data suggested that propofol may play certain positive roles in protecting the kidney from IRI.


Assuntos
Lesão Renal Aguda/prevenção & controle , Propofol/farmacologia , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Lesão Renal Aguda/etiologia , Animais , Apoptose/efeitos dos fármacos , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Propofol/uso terapêutico , Substâncias Protetoras/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/etiologia , Serina-Treonina Quinases TOR/metabolismo , Resultado do Tratamento
17.
Medicine (Baltimore) ; 98(19): e15141, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083151

RESUMO

BACKGROUND: Guardix-SG is a poloxamer-based antiadhesive agent. The aim of this study was to investigate its efficacy in preventing abdominal adhesions in gastric cancer patients undergoing gastrectomy. Few clinical studies have reported that antiadhesive agent reduces the incidence of adhesion after gastrectomy. METHODS: We conducted a multicenter trial from June 2013 and August 2015 in patients with gastric adenocarcinoma undergoing radical gastrectomy. Patients were randomly assigned to the Guardix treatment or control group. Postoperative adhesions were diagnosed based on postoperative symptoms, plain x-ray films, and computed tomography. The primary endpoint of the study was the incidence of small bowel obstruction in the first postoperative year. The secondary end-point was the safety of Guardix-SG. RESULTS: The study included 109 patients in the Guardix group and 105 patients in the control group. The groups were similarly matched with pathological stage, operation type, anastomosis method, midline incision length, and the extent of lymph node dissection. Eight in the Guardix group and 21 in the control group experienced intestinal obstruction during the 1-year follow-up period. The cumulative incidence of small bowel obstruction was significantly lower in the Guardix group compared to that seen in the control group (4.7% vs 8.6% at 6 months and 7.3% vs 20% at 1 year; P = .007, log-rank test). There were no differences in postoperative complications and adverse events. CONCLUSION: Guardix-SG significantly decreased the incidence of intestinal obstruction without affecting the incidence of postoperative complications.


Assuntos
Carboximetilcelulose Sódica/uso terapêutico , Gastrectomia , Ácido Hialurônico/uso terapêutico , Obstrução Intestinal/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Substâncias Protetoras/uso terapêutico , Aderências Teciduais/prevenção & controle , Abdome , Adenocarcinoma/epidemiologia , Adenocarcinoma/cirurgia , Carboximetilcelulose Sódica/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Ácido Hialurônico/efeitos adversos , Incidência , Obstrução Intestinal/epidemiologia , Obstrução Intestinal/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Substâncias Protetoras/efeitos adversos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/cirurgia , Aderências Teciduais/epidemiologia , Aderências Teciduais/etiologia
18.
Medicine (Baltimore) ; 98(19): e15441, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31083174

RESUMO

To observe whether edaravone can protect organs and inhibit pulmonary fibrosis in patients with paraquat poisoning and to provide a method for clinical intervention for paraquat poisoning.Forty-four cases of paraquat poisoning were collected from March 2011 to December 2017 in our hospital. Eighteen cases from March 2011 to November 2013 did not receive edaravone treatment and were considered the control group, and 26 cases from January 2014 to December 2017 were treated with edaravone and were considered the observation group. Injuries to the central nervous system, heart, liver, kidney, and digestive system were evaluated on at 24 hours, 3 days, and 7 days after hospitalization. The expression of serum inflammatory factors (interleukin [IL]-6, IL-10, tumor necrosis factor-α [TNF-α]) and oxidative stress correlation (superoxide dismutase [SOD] and malondialdehyde [MDA]) were assayed at 24 hours, 3 days, and 7 days after being hospitalized. After 7, 14, and 30 days, the changes in pathological lung characteristics in the 2 groups were assessed, and survival rates were calculated.Edaravone significantly increased the serum levels of SOD and obviously markedly reduce the serum levels of IL-6, IL-10, TNF-α, and MDA in patients poisoned with paraquat (P < .05). Edaravone significantly protected the liver (P = .021), cardiovascular (P = .031), and renal (P = .028) organs of patients from paraquat poisoning-induced injury after 7 days but had no significant protection or improvement on respiratory and digestive tract damage. Edaravone delayed the occurrence of pulmonary fibrosis and increase the survival time of patients at 7 and 14 days (P < .05). However, the 1-month follow-up found that edaravone did not reduce pulmonary fibrosis (77.8% vs 73.1%, P = .615) and did not increase the survival rate of the patients (61.1% vs 65.3%, P = .853).Edaravone is beneficial for protecting the kidneys and liver from paraquat poisoning through reducing oxidative stress and inhibiting inflammatory response. It can also inhibit the pulmonary fibrosis process and prolong the survival time of the patients. However, no significant improvements were seen in the probability of pulmonary fibrosis and the survival rate.


Assuntos
Edaravone/uso terapêutico , Paraquat/envenenamento , Substâncias Protetoras/uso terapêutico , Adulto , Biomarcadores/sangue , Citocinas/sangue , Feminino , Humanos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Prognóstico , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/mortalidade , Estudos Retrospectivos
19.
Int J Mol Sci ; 20(10)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126043

RESUMO

Phytochemicals are known to benefit human health by modulating various cellular processes, including cell proliferation, apoptosis, and inflammation. Due to the potential use of phytochemicals as therapeutic agents against human diseases such as cancer, studies are ongoing to elucidate the molecular mechanisms by which phytochemicals affect cellular functions. It has recently been shown that phytochemicals may regulate the expression of microRNAs (miRNAs). MiRNAs are responsible for the fine-tuning of gene expression by controlling the expression of their target mRNAs in both normal and pathological cells. This review summarizes the recent findings regarding phytochemicals that modulate miRNA expression and promote human health by exerting anticancer, photoprotective, and anti-hepatosteatosis effects. Identifying miRNAs modulated by phytochemicals and understanding the regulatory mechanisms mediated by their target mRNAs will facilitate the efforts to maximize the therapeutic benefits of phytochemicals.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Fígado Gorduroso/tratamento farmacológico , MicroRNAs/genética , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Fígado Gorduroso/genética , Fígado Gorduroso/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Promoção da Saúde , Humanos , Neoplasias/genética , Neoplasias/prevenção & controle , Compostos Fitoquímicos/farmacologia , Substâncias Protetoras/farmacologia
20.
J Zoo Wildl Med ; 50(1): 33-44, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31120660

RESUMO

Harmful algal blooms (HABs) occur when excess nutrients allow dinoflagellates to reproduce in large numbers. Marine animals are affected by blooms when algal toxins are ingested or inhaled. In the Gulf of Mexico, near annual blooms of Karenia brevis release a suite of compounds (brevetoxins) that cause sea turtle morbidity and mortality. The primary treatment at rehabilitation facilities for brevetoxin-exposed sea turtles is supportive care, and it has been difficult to design alternative treatment strategies without an understanding of the effects of brevetoxins in turtles in vivo. Previous studies using the freshwater turtle as a model species showed that brevetoxin-3 impacts the nervous and muscular systems, and is detoxified and eliminated primarily through the liver, bile, and feces. In this study, freshwater turtles (Trachemys scripta) were exposed to brevetoxin (PbTx-3) intratracheally at doses causing clear systemic effects, and treatment strategies aimed at reducing the postexposure neurological and muscular deficits were tested. Brevetoxin-exposed T. scripta displayed the same behaviors as animals admitted to rehabilitation centers for toxin exposure, ranging from muscle twitching and incoordination to paralysis and unresponsiveness. Two treatment regimes were tested: cholestyramine, a bile acid sequestrant; and an intravenous lipid emulsion treatment (Intralipidt) that provides an expanded circulating lipid volume. Cholestyramine was administered orally 1 hr and 6 hr post PbTx-3 exposure, but this regime failed to increase toxin clearance. Animals treated with Intralipid (100 mg/kg) 30 min after PbTx-3 exposure had greatly reduced symptoms of brevetoxicosis within the first 2 hr compared with animals that did not receive the treatment, and appeared fully recovered within 24 hr compared with toxin-exposed control animals that did not receive Intralipid. The results strongly suggest that Intralipid treatment for lipophilic toxins such as PbTx-3 has the potential to reduce morbidity and mortality in HAB-exposed sea turtles.


Assuntos
Emulsões Gordurosas Intravenosas/uso terapêutico , Toxinas Marinhas/toxicidade , Neurotoxinas/toxicidade , Oxocinas/toxicidade , Envenenamento/veterinária , Substâncias Protetoras/uso terapêutico , Tartarugas/fisiologia , Animais , Resina de Colestiramina/uso terapêutico , Envenenamento/tratamento farmacológico
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