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1.
J Sci Food Agric ; 100(1): 92-101, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31435952

RESUMO

BACKGROUND: Oyster polypeptides have various biofunctions, such as anti-cancer and anti-oxidative stress, but whether it has the protective effects to primary ovarian failure (POF) remains poorly understand. To address this issue, daily gavage of oyster polypeptides was performed to investigate their protective effect, basing on d-galactose-induced POF model in C57BL/6 female mice. RESULTS: Oyster polypeptides restored the irregular estrous cycles and the abnormal serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and progesterone (P) levels as well as the decreased mRNA expression level of Amh that were induced by d-galactose. The follicle development of POF mice was improved by increasing the primordial follicle ratio and decreasing the atretic follicle number after oral administration of oyster polypeptides. Moreover, in the oyster polypeptides treated mice, the total superoxide dismutase (T-SOD) activity was significantly increased, while the malondialdehyde levels were significantly decreased. The mRNA expression levels of stress-related genes (SOD2, SIRT1 and FOXO3a) were remarkably up-regulated after d-galactose induction, but the up-regulation was weakened or disappeared by the gavage of oyster polypeptides. In addition, oyster polypeptides treatment also reduced the apoptosis of the ovarian granulosa cells and down-regulated the mRNA expression levels of apoptosis-related genes (p53 and Bad but not Bcl-2). CONCLUSION: This study reveals that oyster polypeptides may protect ovary against d-galactose-induced POF by their anti-oxidative stress activity to rescue d-galactose-induced ovarian oxidative damage and therefore to prevent ovarian cells apoptosis, thereby tipping the abnormality trigged by POF to get close to the normal levels. © 2019 Society of Chemical Industry.


Assuntos
Ostreidae/química , Peptídeos/administração & dosagem , Insuficiência Ovariana Primária/tratamento farmacológico , Substâncias Protetoras/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Feminino , Galactose/efeitos adversos , Humanos , Hormônio Luteinizante/metabolismo , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/metabolismo , Ovário/efeitos dos fármacos , Ovário/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/metabolismo , Progesterona/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
2.
J Agric Food Chem ; 67(50): 13948-13959, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31698901

RESUMO

The aim of this study was to investigate the protective effect of punicalagin (PU), which is a main component of pomegranate polyphenols, against liver injury induced by Type 2 diabetes mellitus (T2DM) and to explore the molecular mechanism based on autophagy in vivo and in vitro. In T2DM mice, we found that PU significantly improved liver histology, reversed serum biochemical abnormalities, and increased the autophagosome number in the liver. In HepG2 cells cultured in a high-glucose environment, PU upregulated the glucose uptake level. Both in vivo and in vitro, PU upregulated the expression of autophagy-related proteins, such as LC3b and p62, and reduced the phosphorylated Akt/total Akt and phosphorylated FoxO3a/total FoxO3a protein ratios, and these effects were enhanced by LY294002 (a PI3K/Akt inhibitor). In summary, our current findings suggest that PU protects against liver injury induced by T2DM by restoring autophagy through the Akt/FoxO3a signaling pathway.


Assuntos
Autofagia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Proteína Forkhead Box O3/metabolismo , Taninos Hidrolisáveis/administração & dosagem , Hepatopatias/prevenção & controle , Fígado/lesões , Substâncias Protetoras/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Proteína Forkhead Box O3/genética , Humanos , Fígado/metabolismo , Hepatopatias/etiologia , Hepatopatias/metabolismo , Hepatopatias/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos
3.
Arq Gastroenterol ; 56(4): 333-338, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721967

RESUMO

BACKGROUND: Indigofera suffruticosa Mill (Fabaceae) is abundant in northeastern Brazil and popularly used in the treatment of infectious and inflammatory processes. Several biological properties, such as anti-inflammatory, anticancer, antitumor, hepatoprotective and low toxicity, are reported for this plant. OBJECTIVE: This study investigated hepatoprotective activity and the antioxidant effect of methanolic extract of I. suffruticosa leaves (MEIS) on Swiss albino mice submitted to experimental models of acetaminophen-induced liver injury. METHODS: MEIS (50 mg/kg; p.o.) was standardized according to the LD50 and its hepatoprotective property on Swiss albino mice evaluated during a 7-day period. On the eighth day, the acetaminophen-induced hepatic injury was performed. Histomorphometric analysis of liver tissue, antioxidant activity and serum levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT) and bilirubin were measured. RESULTS: MEIS (50 mg/kg; p.o.) restored serum enzyme levels and results were close to those of positive control (silymarin) when compared to the negative control. Histopathological and histomorphometric analyzes confirmed MEIS hepatoprotective activity, showing reorganization of structural units of cells, nuclei and sinusoidal capillaries of hepatocytes, reducing the damage on liver tissue and increasing organ regeneration rate. MEIS showed high antioxidant potential at concentrations of 1000 and 500 µg/mL. CONCLUSION: This study suggests that MEIS has hepatoprotective activity and high antioxidant potential.


Assuntos
Acetaminofen/toxicidade , Analgésicos não Entorpecentes/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Indigofera/química , Extratos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Masculino , Camundongos
4.
J Surg Oncol ; 120(7): 1220-1226, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31602673

RESUMO

BACKGROUND AND OBJECTIVES: Hyperthermic intrathoracic chemotherapy (HITOC) is used for the treatment of malignant pleural tumors. Although HITOC proved to be safe, postoperative renal failure due to nephrotoxicity of intrapleural cisplatin remains a concern. METHODS: This single-center study was performed retrospectively in patients who underwent pleural tumor resection and HITOC between September 2008 and December 2018. RESULTS: A total of 84 patients (female n = 33; 39.3%) with malignant pleural tumors underwent surgical cytoreduction with subsequent HITOC (60 minutes; 42°C). During the study period, we gradually increased the dosage of cisplatin (100-150 mg/m2 BSA n = 36; 175 mg/m2 BSA n = 2) and finally added doxorubicin (cisplatin 175 mg/m2 BSA/doxorubicin 65 mg; n = 46). All patients had perioperative fluid balancing. The last 54 (64.3%) patients also received perioperative cytoprotection. Overall 29 patients (34.5%) experienced renal insufficiency. Despite higher cisplatin concentrations, patients with cytoprotection showed significantly lower postoperative serum creatinine levels after 1 week (P = .006) and at discharge (P = .020). Also, they showed less intermediate and severe renal insufficiencies (5.6% vs 13.3%). CONCLUSIONS: Adequate perioperative fluid management and cytoprotection seem to be effective in protecting renal function. This allows the administration of higher intracavitary cisplatin doses without raising the rate of renal insufficiencies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Hipertermia Induzida/efeitos adversos , Mesotelioma/terapia , Néfrons/efeitos dos fármacos , Neoplasias Pleurais/terapia , Substâncias Protetoras/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Amifostina/administração & dosagem , Cisplatino/administração & dosagem , Terapia Combinada , Creatinina/sangue , Citoproteção , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade , Neoplasias Pleurais/patologia , Cuidados Pós-Operatórios , Prognóstico , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Tiossulfatos/administração & dosagem , Cavidade Torácica/cirurgia
5.
Khirurgiia (Mosk) ; (9): 66-72, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31532169

RESUMO

OBJECTIVE: The purpose of the study is to determine the correlation of changes in the humoral and tissue components of the hemostasis system with lipid metabolism in case of various urgent surgical diseases, on the basis of which the systemic coagulopathic distress syndrome can be used as the scientific basis for the definition of a new syndrome. MATERIAL AND METHODS: The work includes the results of experimental and clinical laboratory tests. Experiments on dogs: in the first group (n=18) destructive pancreatitis; in the second (n=18) - fecal peritonitis; in the third (n=15), acute obstructive intestinal obstruction; in the fourth (n=16) fecal peritonitis, in the postoperative period, Remaxol (15 ml/kg) was included in the therapy. The analysis of 55 patients with acute peritonitis, operated on for acute appendicitis, perforated gastric or duodenal ulcer, acute intestinal obstruction, acute destructive cholecystitis. In the study group (n=28), Remaxol is included in the postoperative therapy. The state of the humoral and tissue (in the experiment, the tissues of the liver, intestines, kidneys, heart, lungs, pancreas, in the clinic - tissues of the resected organs) components of the hemostasis system was evaluated, a number of lipid metabolism indicators were determined, etc. RESULTS: In the early periods of all investigated urgent diseases of the abdomen, pronounced changes in the system of both humoral and tissue components of the hemostasis system were revealed. The modification of the coagulation system is registered not only in the tissues of the lesion organs, but also in the target organs (system tissue hemocoagulation modifications). The research established one of the most important processes - the trigger of the hemostatic cascade reaction - is membrane-destabilizing (the source of tissue thromboplastin), which is determined by changes in the phospholipid composition of various organs tissues (involved in the pathological process or not in it). Changes in lipid metabolism are due to the activation of phospholipases and membrane lipid peroxidation in tissues. The factual material was the scientific basis for the establishment of a new syndrome. Systemic coagulopathic distress syndrome is a set of pathological processes of the body, the most important component of which is a violation of the phospholipid bilayer of blood cell membranes and organ cells due to oxidative and phospholipase induced phenomena, leading to a coagulopathic condition. It changes understanding of the prevention of thrombohemorrhagic complications, proving the effectiveness of complex therapy, including not only anticoagulants, but also drugs with membrane-stabilizing activity, in particular, Remaxol.


Assuntos
Transtornos da Coagulação Sanguínea/prevenção & controle , Doenças do Sistema Digestório/complicações , Infecções Intra-Abdominais/complicações , Substâncias Protetoras/administração & dosagem , Succinatos/administração & dosagem , Doença Aguda , Animais , Apendicite/complicações , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Colecistite Aguda/complicações , Doenças do Sistema Digestório/fisiopatologia , Cães , Doenças Hematológicas/etiologia , Doenças Hematológicas/fisiopatologia , Doenças Hematológicas/prevenção & controle , Hemostasia/fisiologia , Humanos , Obstrução Intestinal/complicações , Infecções Intra-Abdominais/fisiopatologia , Metabolismo dos Lipídeos/fisiologia , Pancreatite/complicações , Úlcera Péptica Perfurada/complicações , Peritonite/complicações , Síndrome
6.
Food Chem Toxicol ; 133: 110797, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31479713

RESUMO

The aim of this work was to evaluate whether oral administration of Eruca vesicaria, a species of rocket cultivated in Argentina, could modify cyclophosphamide (CP)-induced genotoxicity through modulation of hepatic ABC transporters. Daily oral administration of E. vesicaria fresh leaves juice (1.0, 1.4 and 2.0  g/kg) for 14 days did not alter genotoxicity biomarkers -alkaline comet assay and micronucleus test -in neither male nor female mice. Instead, repeated intake of this cruciferous decreased CP-induced DNA damage dose-dependently and it caused hepatic overexpression of P-glycoprotein (P-gp; 1.4 and 2.0  g/kg) and multidrug resistance protein 2 (MRP2; 2.0  g/kg), but not breast cancer resistance protein (Bcrp). The antigenotoxic effect of E. vesicaria was prevented by 50 mg/kg verapamil (P-gp inhibitor) or 10 mg/kg indomethacin (MRP2 inhibitor). In turn, CP-induced cytotoxicity (10 mM, 24 h) on human hepatoma cells (HepG2/C3A) was significantly reduced by preincubation with E. vesicaria (1.4 mg/ml; 48 h); this effect was absent when CP was coincubated with 35 µM verapamil, 80 µM indomethacin or 10 µM KO-143 (BCRP inhibitor). Altogether, these results allow us to demonstrate that repeated intake of E. vesicaria exhibited antigenotoxicity, at least in part, by induction of hepatic ABC transporters in vivo in mice as well as in vitro in human liver cells. This could account for other diet-drug interactions.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Brassica/química , Mutagênese/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Administração Oral , Animais , Linhagem Celular Tumoral , Ciclofosfamida/farmacologia , Dano ao DNA/efeitos dos fármacos , Feminino , Sucos de Frutas e Vegetais , Humanos , Fígado/metabolismo , Masculino , Camundongos , Mutagênicos/farmacologia , Extratos Vegetais/administração & dosagem , Folhas de Planta/química , Substâncias Protetoras/administração & dosagem
7.
In Vivo ; 33(5): 1455-1461, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31471392

RESUMO

BACKGROUND/AIM: Idiopathic pulmonary fibrosis (PF) is a fatal disorder of unknown aetiology with limited treatment options. Chitosan has antibacterial, antifungal, antioxidant, antitumour, and anti-inflammatory effects. This study aimed to investigate the effects of chitosan administration on bleomycin (BLM)-induced PF in rats. MATERIALS AND METHODS: A PF rat model was established by endotracheal instillation of 5 mg/kg BLM; then, chitosan was administered in drinking water for 3 weeks. Histology, cell counts, and cytokine responses in the bronchoalveolar lavage fluid (BALF) and weight measurements (body and lung) were analyzed to assess its therapeutic effects. RESULTS: Chitosan administration tended to reduce transforming growth factor (TGF)-ß1 and interferon (IFN)-γ levels in BALF, and histopathological examination confirmed that chitosan attenuated the degree of inflammation and fibrosis in the lung. CONCLUSION: This study revealed that oral chitosan exhibits potential antifibrotic effects, as measured by decreased proinflammatory cytokine levels and histological evaluation, in a BLM-induced PF rat model.


Assuntos
Bleomicina/efeitos adversos , Quitosana/administração & dosagem , Substâncias Protetoras/administração & dosagem , Fibrose Pulmonar/etiologia , Administração Oral , Animais , Biópsia , Modelos Animais de Doenças , Progressão da Doença , Imuno-Histoquímica , Masculino , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Ratos , Resultado do Tratamento
8.
Fish Shellfish Immunol ; 93: 1100-1110, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31422179

RESUMO

Nrf2/Keap1 pathway is associated with oxidative stress. l-carnitine is currently under preclinical evaluation as a antioxidant, but the use of l-carnitine in aquaculture has been poorly evaluated and so far no mechanism has been demonstrated. Here, we explored the effects of l-carnitine in vitro and in vivo and discussed the possible molecular mechanisms involved. Firstly, Nrf2-siRNA significantly knocked down the mRNA level of Nrf2 in FHM cells. Thus, the activities of antioxidant enzymes (T-SOD, CAT, GSH-PX) and the level of antioxidant substance (GSH) and the level of MDA showed that Nrf2-siRNA pretreatment weakened the protective effect of l-carnitine. Moreover, the mRNA levels of Keap1, Nrf2, Maf and HO-1 indicated that l-carnitine regulated Nrf2/Keap1 activation. Furthermore, oxidized fish oil remarkably suppressed growth in Rhynchocypris lagowski Dybowski, and the lower antioxidant capacity was also observed in liver. According to the results of immune related indexes (the levels of IL-1ß, TNF-α, LZM, AKP) in serum and the mRNA levels of immune related genes (NF-κB, IL-1ß, TNF-α, IL-8, IL-10 and TGF-ß) in liver, oxidized fish oil also induced inflammatory response in fish. Also, l-carnitine supplementation can relieve this bad condition. In conclusion, l-carnitine regulated Nrf2/Keap1 activation in vitro and in vivo and protected oxidized fish oil-induced inflammation response by inhibiting the NF-κB signaling pathway in Rhynchocypris lagowski Dybowski.


Assuntos
Carnitina/metabolismo , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Proteínas de Peixes/metabolismo , Substâncias Protetoras/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Carnitina/administração & dosagem , Proteínas de Transporte/metabolismo , Linhagem Celular , Cyprinidae/genética , Cyprinidae/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Doenças dos Peixes/tratamento farmacológico , Óleos de Peixe/farmacologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/veterinária , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Oxirredução , Estresse Oxidativo , Substâncias Protetoras/administração & dosagem , Distribuição Aleatória
9.
Fish Shellfish Immunol ; 93: 934-939, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31404633

RESUMO

Tightened regulations and an environmentally friendly approaches in fish production have greatly reduced the use of antibiotics but green solutions are continuously being explored. The use of functional feed may have a potential in the aquaculture sector in securing biomass and minimizing the loss from disease. In the present study, we tested the concept that blood from the fish slaughterhouse can be used for mass purification of specific antibodies which subsequently can be used for feeding fish and thereby confer protection against diseases. IgM was purified from serum from Yersinia ruckeri vaccinated rainbow trout and an IgM sandwich ELISA was developed for quantification of rainbow trout IgM. The purified IgM was encapsulated in alginate microparticles and top-coated in fish feed. IgM re-extracted from the alginate microparticles was shown to retain high reactivity towards Y. ruckeri antigens indicating that its bioactivity remained intact after encapsulation. IgM release from the alginate microparticles was only observed at high pH (pH 8.2) and minimal at low pH, indicating protection of IgM at low pH in the fish stomach during passage. In a feeding - challenge experiment (feeding 1 week before Y. ruckeri challenge and for two weeks following challenge), a statistically non-significant 10% lower mortality was observed in the high dose (400 µg IgM/fish/day fed over 3 weeks) group.


Assuntos
Doenças dos Peixes/imunologia , Imunoglobulina M/metabolismo , Oncorhynchus mykiss/imunologia , Substâncias Protetoras/metabolismo , Yersiniose/veterinária , Yersinia ruckeri/efeitos dos fármacos , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Doenças dos Peixes/tratamento farmacológico , Imunoglobulina M/administração & dosagem , Substâncias Protetoras/administração & dosagem , Yersiniose/tratamento farmacológico , Yersiniose/imunologia
10.
Fish Shellfish Immunol ; 93: 1067-1075, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31386909

RESUMO

Fishmeal is the main source of protein in the shrimp feed industry and is normally derived from trash fish. As such, the production of fishmeal has an adverse effect on the marine environment by taking away small and juvenile fish, leading to depletion of marine species. There is a need for alternative sources of protein which will substitute fishmeal in the aquaculture industry. This study evaluated the components and nutritional efficacy of bioflocs, which were used to substitute fishmeal protein. The effect of bioflocs diets on growth performance, survival rate, and immune response in shrimp compared to normal fishmeal feed were determined. Bioflocs were harvested from the shrimp ponds (C:N ratio >12:1) at Shrimp Village, Chaiya district, Surat Thani, Thailand. The total protein in bioflocs was about 48% and the total lipid was about 5% (dried weight) and the percentages of essential amino acids (EAA) and fatty acids (EFA) in bioflocs were similar to those of fishmeal feed. Shrimp fed with the different dietary bioflocs feed regimens [% to replace fishmeal; 0% (B0), 25% (B25), 50% (B50), 75% (B75), and 100% (B100)] for 42 days revealed that all growth parameters were almost similar to those of the control shrimp (shrimp fed with normal fishmeal, B0) including final body weight, weight gain, specific growth rate, and feed conversion ratio. Remarkably, the survival rates, the levels of immune parameters, and expression of immune genes (proPO-I, PEN-4 and dicer) were significantly higher in bioflocs fed shrimp, especially in B25 and B50 shrimp. Moreover, B25 and B50 bioflocs fed shrimp showed notably increased survival rates following Vibrio parahaemolyticus (V. parahaemolyticus) infection. In conclusion, the present study demonstrates that shrimp survival and immunity are enhanced by biofiocs substituted fishmeal. Significantly, the bioflocs diets activated the immune response to prevent V. parahaemolyticus infection.


Assuntos
Ração Animal/análise , Imunidade Inata/efeitos dos fármacos , Penaeidae/imunologia , Substâncias Protetoras/farmacologia , Vibrio parahaemolyticus/fisiologia , Animais , Aquicultura , Dieta , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Penaeidae/microbiologia , Substâncias Protetoras/administração & dosagem
11.
Am J Chin Med ; 47(5): 1099-1112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366207

RESUMO

Asthma is the most prevalent chronic respiratory disease worldwide. Garlic extracts have long been used as a food source and in traditional medicine. Crude extracts of garlic are used as an anti-inflammatory agent and have been reported to exhibit antiasthmatic properties. However, molecular mechanisms of garlic extracts in the context of antiasthmatic airway inflammation are still unclear. In this study, the antiasthmatic effect of garlic extracts on Th1, Th2, and Th3 cytokine profiles and immunoregulatory mechanism were explored using an animal model of allergic asthma. Garlic extracts significantly reduced total inflammatory cell counts and eosinophil infiltration and decreased the production of Dermatophagoides pteronyssinus IgE in serum and Th1/Th2/Th3 cytokine in bronchoalveolar fluid. Enzyme-linked immunosorbent assay analysis demonstrated that garlic extracts downregulated the levels of cytokines and chemokines, namely Th2-related IL-4, IL-5, and IL-13; but they simultaneously upregulated Th1-related IFN-γ, IL-12, and Th3-related IL-10 and TGF-ß expression in BALF. The mechanism may be ascribed to the modulation of Th1-, Th2-, and Th3-related cytokine imbalance.


Assuntos
Asma/prevenção & controle , Alho/química , Extratos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Alérgenos/efeitos adversos , Animais , Anti-Inflamatórios/administração & dosagem , Asma/induzido quimicamente , Asma/genética , Asma/imunologia , Feminino , Humanos , Imunoglobulina E/imunologia , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-5/genética , Interleucina-5/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia
12.
BMC Complement Altern Med ; 19(1): 182, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337380

RESUMO

BACKGROUND: Increase oxidative trauma is the main cause behind Cisplatin (CP) induced cardiotoxicity which restricts its clinical application as anti-neoplastic prescription. Acacia hydaspica is a natural shrub with diverse bioactivities. Acacia hydaspica ethyl acetate extract (AHE) ameliorated drug-induced cardiotoxicity in animals with anti-oxidative mechanisms. Current study aimed to evaluate the protective potential of A. hydaspica against cisplatin-induced myocardial injury. METHODS: Rats were indiscriminately distributed into six groups (n = 6). Group 1: control; Groups 2: Injected with CP (7.5 mg/kg bw, i.p, single dose) on day 16; Group 3: Treated for 21 days with AHE (400 mg/kg b.w, oral); Group 4: Received CP injection on day 16 and treated with AHE for 5 days post injection; Group 5: Received AHE (400 mg/kg b.w/day, p.o.) for 21 days and CP (7.5 mg/kg b.w., i.p.) on day 16; Group 6: Treated with silymarin (100 mg/kg b.w., p.o.) after 1 day interval for 21 days and CP injection (7.5 mg/kg b.w., i.p.) on day 16. On 22nd day, the animals were sacrificed and their heart tissues were removed. Cisplatin induced cardiac toxicity and the influence of AHE were evaluated by examination of serum cardiac function markers, cardiac tissue antioxidant enzymes, oxidative stress markers and histology. RESULTS: CP inoculation considerably altered cardiac function biomarkers in serum and diminished the antioxidant enzymes levels, while increased oxidative stress biomarkers in cardiac tissues AHE treatment attenuated CP-induced deteriorations in creatine kinase (CK), Creatine kinase isoenzymes MB (CK-MB), cardiac Troponin I (cTNI) and lactate dehydrogenase (LDH) levels and ameliorated cardiac oxidative stress markers as evidenced by decreasing lipid peroxidation, H2O2 and NO content along with augmentation in phase I and phase II antioxidant enzymes. Additionally, CP inoculation also induced morphological alterations which were ameliorated by AHE. In pretreatment group more significant protection was observed compared to post-treatment group indicating preventive potential of AHE. The protective potency of AHE was comparable to silymarin. CONCLUSION: Results demonstrate that AHE attenuated CP induce cardiotoxicity. The polyphenolic metabolites and antioxidant properties of AHE might be responsible for its protective influence.


Assuntos
Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Traumatismos Cardíacos/prevenção & controle , Coração/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Acacia , Animais , Antioxidantes/administração & dosagem , Traumatismos Cardíacos/etiologia , Humanos , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Substâncias Protetoras/química , Ratos , Ratos Sprague-Dawley , Silimarina/administração & dosagem , Silimarina/análise
13.
Sci Total Environ ; 692: 233-239, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31349164

RESUMO

Because of their biocide properties, silver nanoparticles (AgNPs) are present in numerous consumer products. The biocidal properties of AgNPs are due to both the interactions between AgNP and cell membranes and the release of dissolved silver (Ag+). Recent studies emphasized the role of different nanoparticle coatings in complexing and storing Ag+. In this study, the availability of dissolved silver in the presence of algae was assessed for three AgNPs with different silver contents (59%, 34% and 7% of total Ag), silver core sizes and casein shell thicknesses. The impact of ionic silver on the photosynthetic yield of Chlamydomonas reinhardtii was used as a proxy to estimate the amount of ionic silver toxically active during in vivo assays. The results showed that cysteine, a strong silver ligand, mitigated the toxicity of AgNPs in all cases, demonstrating the key role of Ag+ in this toxicity. The results showed that the AgNPs presenting an intermediate level of silver (34%) were 10 times more effective in terms of total mass (EC50 ten times smaller) than those presenting more (59%) or less (7%) silver. The higher toxicity was due to the higher release of Ag+ under biotic conditions due to the high surface/mass ratio of the nanoparticle silver core. Protein shells played a minor role in altering the availability of Ag+, probably acting as intermediate reservoirs. This study highlighted the utility of a very sensitive biological endpoint (i.e., algal photosynthesis) for the optimization of ionic silver delivery by nanomaterials.


Assuntos
Chlamydomonas reinhardtii/efeitos dos fármacos , Nanopartículas Metálicas/efeitos adversos , Fotossíntese/efeitos dos fármacos , Prata/efeitos adversos , Disponibilidade Biológica , Chlamydomonas reinhardtii/metabolismo , Cisteína/administração & dosagem , Relação Dose-Resposta a Droga , Íons/efeitos adversos , Substâncias Protetoras/administração & dosagem
14.
Cell Mol Biol (Noisy-le-grand) ; 65(5): 24-31, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31304902

RESUMO

This study was carried out to evaluate the preventive and curative effects of Pilose antler against osteoporosis due to kidney deficiency, and investigate its potential mechanism of action. A model of osteoporosis due to kidney deficiency was established in rats using bilateral ovariectomy. Pilose antler polypeptide (PAP), Pilose antler polysaccharide (PAP'), and their mixture (PAP+PAP') were separately administered to the rats for 12 weeks, with progynova and xianlingubao tablets (XLGB) as the positive control groups. We determined the bone mineral density (BMD) and uterus Index of the rats. Osteoblastic bone metabolism-related indices in serum and bone tissue were measured with ELISA. Western blotting and RT-PCR were used to investigate the protein and mRNA expressions of Bmp-2, Smad1, Smad5, Runx2 in bone tissue. The morphology of bone tissue was determined using immunohistochemical methods. Compared with control group, PAP, PAP', PAP+PAP' increased BMD and regulated bone metabolism indices in serum and bone tissue. Treatment with Pilose antler up-regulated the mNRA and protein expressions of Bmp-2, Smad1, Smad5 and Runx2. Immunohistochemical staining showed that Bmp-2, Smad1, Smad5 and Runx2 were stained brown, indicating that all of them were positive. There were abnormal changes in the protein expressions of Bmp-2, Smad1, Smad5 and Runx2 in bone tissue, which may be an important mechanism underlying the development of kidney deficiency osteoporosis. Moreover, PAP, PAP' and PAP+PAP' had some preventive effects on osteoporosis, probably via the activation of the Bmp-2/Smad1 and Smad5/Runx2 signaling pathways through induction of high expressions of their mRNAs and proteins.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Osteoporose/etiologia , Peptídeos/farmacologia , Substâncias Protetoras/farmacologia , Insuficiência Renal/complicações , Animais , Densidade Óssea , Proteína Morfogenética Óssea 2/metabolismo , Osso e Ossos/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/prevenção & controle , Ovariectomia/efeitos adversos , Peptídeos/administração & dosagem , Peptídeos/uso terapêutico , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/uso terapêutico , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteína Smad1/metabolismo , Proteína Smad5/metabolismo , Útero/patologia
15.
Cell Mol Biol (Noisy-le-grand) ; 65(5): 32-37, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31304903

RESUMO

To investigate the effects of emodin on learning and memory and protein kinase C (PKC) signaling pathway in Alzheimer's disease (AD) model mice. 60 APP/PS1 double transgenic AD mice were selected as model mice at the age of 7-8 months, 36 healthy male C57BL/6 mice served as the control group. Morris water maze method and passive avoidance experiment were used to evaluate the memory ability of mice. The thiazole blue (MTT) method and the lactate dehydrogenase (LDH) cytotoxicity test kit were used to evaluate the effect of emodin on the cell viability of hippocampal neurons in HT22 mice treated with ß-amyloid peptide 1-42 (Aß1-42). The effect of emodin on PKC levels was explored using the modified Takai method and Western blotting. Behavioral test results showed that the escape latency of the mice in the model group was longer than that in the control group (P<0.05), and the escape latency was significantly shortened given a emodin prognosis. The MTT and LDH test results showed that emodin to Aß- overexpression induced the protective effect of hippocampus cells in HT22 mice. Western blot analysis showed that the phosphorylation level of PKC in mice increased significantly after emodin administration. Emodin can attenuate oxidative stress and inflammatory response in Alzheimer's model mice by activating PKC pathway, thereby improving cognitive function.


Assuntos
Doença de Alzheimer/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Emodina/farmacologia , Substâncias Protetoras/farmacologia , Proteína Quinase C/metabolismo , Transdução de Sinais/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Emodina/administração & dosagem , Emodina/uso terapêutico , Hipocampo/patologia , Inflamação/metabolismo , Masculino , Memória/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Fosforilação/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/uso terapêutico
16.
Cell Mol Biol (Noisy-le-grand) ; 65(5): 54-58, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31304907

RESUMO

Alzheimer's disease (AD) is a high-incidence neurodegenerative disease with complex and diverse pathogenesis. With aging of the population and continuous improvement of living standards, the incidence of AD is on the increase. Therefore, there is need to develop more effective AD drugs in order to improve the quality of life of the elderly. Sakuranetin (SAK) is a dihydroflavonoid compound extracted from plants. It has many physiological properties. In this study, the effect of SAK on spatial discrimination in a rat model of cognitive dysfunction exposed to D-galactose was investigated with respect to its effect on malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, and on the expressions of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nuclear factor-κB inhibitory factor-α (IκBα) in hippocampus of rats. The results obtained suggest that SAK may exert protective effects on brain cells through anti-oxidation mechanism. Moreover, the improvement in learning and memory impairment by SAK may also be related to the inhibition of inflammatory mediators in brain tissue. These findings provide scientific evidence that can be exploited for more effective treatment of Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Flavonoides/farmacologia , Hipocampo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Modelos Animais de Doenças , Flavonoides/administração & dosagem , Galactose/farmacologia , Glutationa Peroxidase/metabolismo , Hipocampo/metabolismo , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , Memória/efeitos dos fármacos , Inibidor de NF-kappaB alfa/metabolismo , Oryza/química , Extratos Vegetais/administração & dosagem , Substâncias Protetoras/administração & dosagem , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Navegação Espacial/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
17.
Ann Clin Lab Sci ; 49(3): 361-367, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31308036

RESUMO

OBJECTIVE: We aim to investigate the protective effects of compound Cotinus coggygria oral liquid on acute liver injury of mice induced by D-galactosamine (GalN). METHODS: Acute liver injury mouse model was established by D-GalN. A total of 72 mice were randomly divided into the blank group, model group constructed by D-GalN, Huganning tablet-treated model group (1.0125 g/kg, as the positive control group), and large (30 ml/kg), medium (15 ml/kg) and small (7.5 ml/kg) doses of compound Cotinus coggygria oral liquid-treated model groups. SPSS 17.0 was used for statistical analysis. RESULTS: Compared to the blank group, the model group demonstrated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice serum and liver homogenate was significantly increased (P<0.01), alteration of liver tissue structure and obvious hepatic cytolysis necrosis, indicating successfully establishement of acute liver injury model. Compared with the model group, the liver index is significantly decreased in large and medium doses of compound Cotinus coggygria oral liquid treated groups (P<0.05), and the effects of large doses of compound Cotinus coggygria are more significant (P<0.01). Furthermore, different doses of compound Cotinus coggygria oral liquid can significantly reduce the activity of mice serum ALT, AST (P<0.01). Large and medium doses of compound Cotinus coggygria oral liquid significantly reduce the activities of ALT (P<0.01) and AST in liver homogenate (P<0.05), and also improve the structure of liver tissues, decreasing the amount of hepatic necrosis, which is associated with liver cell regeneration. CONCLUSION: Compound Cotinus coggygria oral liquid has protective effects on mice acute liver injury induced by D-GalN.


Assuntos
Anacardiaceae/química , Fígado/lesões , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Doença Aguda , Administração Oral , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Modelos Animais de Doenças , Feminino , Galactosamina , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos
18.
J Med Food ; 22(9): 885-895, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31274380

RESUMO

We have previously demonstrated the hepatoprotective effect of Schisandra chinensis polysaccharides (SCP) against the liver injury induced by alcohol, high-fat diet, and carbon tetrachloride in mice. In this study, we investigated the effect of SCP against the immunological liver injury induced by concanavalin A (Con A) in mice. The results showed that SCP could significantly reduce the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in the serum of mice with immunological liver injury. SCP could significantly decrease the content of malondialdehyde (MDA) and nitric oxide (NO) and increase the activity of superoxide dismutase (SOD) and glutathione (GSH) in the liver tissue. SCP could significantly increase the number of CD4+ and decrease the number of CD8+ in the peripheral blood, and elevate the ratio of CD4+/CD8+. SCP could significantly downregulate the expression of Kelch-like ECH-associated protein 1 (Keap1) and upregulate the expression of nuclear factor-erythroid 2-related factor2 (Nrf2) and downstream gene heme oxygenase-1 (HO-1), and downregulate the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), and nuclear factor-kappa B (NF-κB) proteins. This study indicates that SCP can reduce the release of a large number of inflammatory factors to inhibit the oxidative stress in mice with the immunological liver injury induced by Con A, and its mechanism is closely related to the regulation of Nrf2/antioxidant response element and TLR4/NF-κB signaling pathways.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Hepatopatias/prevenção & controle , Fígado/lesões , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Polissacarídeos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Schisandra/química , Receptor 4 Toll-Like/imunologia , Animais , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias/genética , Hepatopatias/imunologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fator 2 Relacionado a NF-E2/genética , NF-kappa B/genética , Óxido Nítrico/imunologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
19.
Mar Drugs ; 17(7)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269758

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a global epidemic, and there is no standard and efficient therapy for it. Chitosan oligosaccharide (COS) is widely known to have various biological effects, and in this study we aimed to evaluate the liver-protective effect in diet-induced obese mice for an enzymatically digested product of COS called COS23 which is mainly composed of dimers and trimers. An integrated analysis of the lipidome and gut microbiome were performed to assess the effects of COS23 on lipids in plasma and the liver as well as on intestinal microbiota. Our results revealed that COS23 obviously attenuated hepatic steatosis and ameliorated liver injury in diet-induced obese mice. The hepatic toxic lipids-especially triglycerides (TGs) and free fatty acids (FFAs)-were decreased dramatically after COS23 treatment. COS23 regulated lipid-related pathways, especially inhibiting the expressions of FFA-synthesis-related genes and inflammation-related genes. Furthermore, COS23 could alter lipid profiles in plasma. More importantly, COS23 also decreased the abundance of Mucispirillum and increased the abundance of Coprococcus in gut microbiota and protected the intestinal barrier by up-regulating the expression of tight-junction-related genes. In conclusion, COS23, an enzymatically digested product of COS, might serve as a promising candidate in the clinical treatment of NAFLD.


Assuntos
Quitosana/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Obesidade/complicações , Oligossacarídeos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Administração Oral , Animais , Quitosana/química , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Ácidos Graxos não Esterificados/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade/etiologia , Oligossacarídeos/química , Substâncias Protetoras/química , Triglicerídeos/metabolismo
20.
Int J Biol Macromol ; 137: 346-357, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31260769

RESUMO

Oxidative stress plays a central role in the incidence of liver injury. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a key protein regulator of antioxidant response elements (ARE)-mediated gene expression. Thus, Nrf2 can be regarded as a plausible therapeutic target during liver injury. ß-Carotene is implicated as one of the important antioxidant with diverse health benefits. The delivery of ß-carotene to the target tissue has been debatable due to its low bioavailability, poor water solubility and instability. Here, a nanocomposite of ß-carotene with reduced graphene oxide (ßC-rGO) has been developed to demonstrate its pronounced effect in regulating Nrf2 to trigger protection against diethylnitrosamine (DEN)-induced hepatic fibrosis in rats. The rGO and ßC-rGO samples were characterised by scanning electron microscopy (SEM), energy dispersive X-ray (EDX), transmission electron microscopy (TEM) and Fourier transform infrared (FTIR) spectroscopy. Progress of disease was monitored through ultrasonography, in vitro liver and serum biochemistry (alanine transaminase, aspartate transaminase, alkaline phosphatase, bilirubin, lipid peroxidation, protein carbonyls, superoxide dismutase, catalase, glutathione-S-transferase, Nrf2, vitamin-A, retinol dehydrogenase), histopathology, confocal and ultrastructural studies. In fibrotic animals liver biochemistry was significantly altered along with massive changes in liver anatomy. ßC-rGO ameliorates experimental fibrogenesis and restores liver functioning due to increased availability of ß-carotene in the liver. It is suggested that ßC-rGO nanocomposite promotes cellular antioxidant status via upregulation of Nrf2 protein factor and invigorate hepatic stellate cells (HSCs) through restoring vitamin-A.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/etiologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Dietilnitrosamina/efeitos adversos , Grafite , Fator 2 Relacionado a NF-E2/metabolismo , Nanocompostos/química , beta Caroteno/administração & dosagem , Animais , Biomarcadores , Doença Hepática Crônica Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Modelos Animais de Doenças , Grafite/química , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Função Hepática , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Ratos , Ultrassonografia , beta Caroteno/química
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