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1.
Medicine (Baltimore) ; 99(28): e20934, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664090

RESUMO

This study aimed to investigate the myocardial protective effect of liquid sodium phosphocreatine cardiac arrest in extracorporeal circulation surgery treating infants with atrial septal defects.Eighty-four infants with atrial septal defects who required extracorporeal circulation surgery treatment at our hospital from January 2016 to June 2018 were divided into an observation group and a control group through a digitally randomized method, with 42 cases in each group. The control group adopted the conventional modified St Thomas II high potassium cold liquid crystal cardiac arrest, while the observation group adopted the liquid sodium phosphocreatine cardiac arrest.The myocardial enzyme indexes of the 2 groups 3, 6, 12, and 24 hours postoperatively were higher than before establishing the cardiopulmonary bypass and the enzyme indexes of the control group at the same time were higher than that of the observation group; adenosine triphosphate, adenosine diphosphate, and other energy levels and the postoperative recovery rate energy levels of the observation group were higher than those in the control group, the difference was statistically significant (P < .05).Liquid sodium phosphocreatine cardiac arrest used in extracorporeal circulation surgery treating infants with atrial septal defects can reduce myocardial ischemia-reperfusion injury, maintain energy supply during ischemia, strengthen the St Thomas II effect, and aid postoperative cardiac function recovery of high potassium cold liquid crystal cardiac arrest used in infants with atrial septal defects and treated with extracorporeal circulation surgery.


Assuntos
Ponte Cardiopulmonar/métodos , Cardiotônicos/farmacologia , Parada Cardíaca Induzida/métodos , Comunicação Interatrial/cirurgia , Fosfocreatina/farmacologia , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Cardiotônicos/administração & dosagem , Estudos de Casos e Controles , Pré-Escolar , Circulação Extracorpórea/métodos , Feminino , Parada Cardíaca/induzido quimicamente , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/tratamento farmacológico , Humanos , Lactente , Masculino , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/química , Miocárdio/enzimologia , Preservação de Órgãos/métodos , Fosfocreatina/administração & dosagem , Período Pós-Operatório , Cloreto de Potássio/administração & dosagem , Cloreto de Potássio/farmacologia , Substâncias Protetoras/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos
2.
J Environ Pathol Toxicol Oncol ; 39(1): 89-99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479015

RESUMO

Oxidative stress and inflammation are regarded as prime reasons for the progression and development of diabetic retinopathy. Currently, nuclear factor erythroid-2-related factor 2 (Nrf2), thioredoxin interacting protein (TXNIP) and NLRP3 inflammasome pathways are under increasing focus in research on oxidative stress and inflammation-related diseases. On the other hand, tilianin (TN) has received much attention because of its various pharmacological properties. Based on results of these studies, this investigation was performed to inspect the therapeutic efficiency of TN on the retina in diabetic rats. Rats were arbitrarily assigned to three groups: control group, diabetic group, and diabetic plus TN (20 mg/ kg body weight for 42 days, orally) group. TN supplementation in diabetic rats, their food intake, fasting blood glucose status, glycosylated hemoglobin (HbA1c) levels were drastically reduced, and there was a marked augmentation in serum insulin status. TN treatment of diabetic rats increased mRNA expression of Nrf2 and its target gene, HO-1, and noticeably decreased the malondialdehyde status. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidases (GPX) were increased relative to diabetic rats. Furthermore, administering TN to the diabetic rats resulted in decreased expression of TXNIP, NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, and IL-1ß proteins and decreased distribution of TXNIP, NLRP3, ASC, and caspase-1 proteins in retinas. In addition, TN treatment ameliorated morphological and morphometric changes in the retinas of diabetic rats. Together, all of these findings provide clear evidence that TN treatment of diabetic rats attenuated diabetic retinal changes through its hypoglycemic, antioxidant, and anti-inflammatory properties. The antioxidant and anti-inflammatory effects in diabetic retinas occur at least in part through the modulation of Nrf2/TXNIP/NLRP3 inflammasome pathways, which may have remedial benefits in the healing of diabetic retinopathy.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Flavonoides/farmacologia , Glicosídeos/farmacologia , Inflamassomos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ração Animal/análise , Animais , Dieta , Suplementos Nutricionais/análise , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Retina/patologia
3.
Braz J Med Biol Res ; 53(7): e9271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520202

RESUMO

Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.


Assuntos
Acetatos/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Tosse/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Quinolinas/uso terapêutico , RNA Longo não Codificante/metabolismo , Animais , Asma/sangue , Criança , Pré-Escolar , Tosse/sangue , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
4.
Acta Cir Bras ; 35(4): e202000401, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555935

RESUMO

PURPOSE: To evaluate the effect of N-Acetylcysteine (NAC) in newborn rats submitted to hypoxia and reoxygenation (H/R) conditions in an experimental model of necrotizing enterocolitis. METHODS: Eight pregnant rats and their 70 cubs were used (5 groups) and exposed to H/R conditions and received NAC at different times. The animals in the H/R groups were placed in a gas chamber (100% CO2) for 10 minutes and then reoxygenated for 10 minutes (100% O2), twice a day for the first three days of life, with a six-hour span between events. On the third day of life, the animals were anesthetized, laparotomized and the intestines were resected. RESULTS: The H/R and NAC groups showed changes in the intestinal wall in relation to the number, height and width of the villi when compared to the control group (p<0.0001), but with better preservation of structures in the NAC group. There were no differences between groups regarding the number (%) of mitoses. CONCLUSION: The administration of NAC decreased the lesions in the intestinal wall of rats submitted to H/R, therefore suggesting that this drug can be used to prevent the development of necrotizing enterocolitis in newborns.


Assuntos
Acetilcisteína/farmacologia , Enterocolite Necrosante/prevenção & controle , Hipóxia/patologia , Íleo/efeitos dos fármacos , Íleo/patologia , Substâncias Protetoras/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Masculino , Gravidez , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
5.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(1): 73-76, 2020 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-32476376

RESUMO

OBJECTIVE: To find if edaravone can play a protective role in a mouse model of pulmonary oxygen toxicity and explore the intervention mechanism. METHODS: Thirty male C57BL/6 mice were randomly divided into 3 groups(Air +Vehicle, Hyperbaric oxygen(HBO) +Vehicle and HBO + Edaravone). Mice were either given edaravone (5 mg/(kg·d)) in sterilized water or a sterilized water vehicle for 3 days before oxygen exposure. Mice in HBO groups were exposed to 0.23 MPa hyperoxia (≥95% O2) for 6 h. Lung tissues were collected and the wet/dry ratio of lung were analyzed. For histologic analysis, lung sections were stained with hematoxylin and eosin (HE). Proinflammatory cytokine levels and antioxidant enzyme activities in lungs were determined by using ELISA kits. The expression levels of pro-apoptosis protein were determined with Western blot analysis. RESULTS: Edaravone treatment could significantly reduce lung permeability, decrease tissue pro-apoptosis protein (cleaved-caspase3) and inflammation (IL-1ß). However, edaravone treatment had no effect on antioxidant enzyme activities. CONCLUSION: These results showed that edaravone treatment had a protective role in pulmonary oxygen toxicity through curbing inflammation and apoptosis.


Assuntos
Edaravone/uso terapêutico , Hiperóxia/tratamento farmacológico , Oxigênio/toxicidade , Substâncias Protetoras/uso terapêutico , Animais , Apoptose , Inflamação , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória
6.
Life Sci ; 254: 117776, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32437790

RESUMO

AIMS: Rg1 is the most active component of traditional Chinese medicine ginseng, having anti-aging and anti-oxidative stress features in multiple organs. Cellular senescence of hepatocytes is involved in the progression of a wide spectrum of chronic liver diseases. In this study, we investigated the potential benefits and mechanism of action of Rg1 on aging-driven chronic liver diseases. MATERIALS AND METHODS: A total of 40 male C57BL/6 mice were randomly divided into four groups: control group; Rg1 group; Rg1+d-gal group; and d-gal group. Blood and liver tissue samples were collected for determination of liver function, biochemical and molecular markers, as well as histopathological investigation. KEY FINDINGS: Rg1 played an anti-aging role in reversing d-galactose induced increase in senescence-associated SA-ß-gal staining and p53, p21 protein in hepatocytes of mice and sustained mitochondria homeostasis. Meanwhile, Rg1 protected livers from d-galactose caused abnormal elevation of ALT and AST in serum, hepatic steatosis, reduction in hepatic glucose production, hydrogenic degeneration, inflammatory phenomena including senescence-associated secretory phenotype (SASP) IL-1ß, IL-6, MCP-1 elevation and lymphocyte infiltration. Furthermore, Rg1 suppressed drastic elevation in FOXO1 phosphorylation resulting in maintaining FOXO1 protein level in the liver after d-galactose treatment, followed by FOXO1 targeted antioxidase SOD and CAT significant up-regulation concurrent with marked decrease in lipid peroxidation marker MDA. SIGNIFICANCE: Rg1 exerts pharmaceutic effects of maintaining FOXO1 activity in liver, which enhances anti-oxidation potential of Rg1 to ameliorate SASP and to inhibit inflammation, also promotes metabolic homeostasis, and thus protects livers from senescence induced fatty liver disease. The study provides a potential therapeutic strategy for alleviating chronic liver pathology.


Assuntos
Fígado Gorduroso/metabolismo , Fígado Gorduroso/prevenção & controle , Proteína Forkhead Box O1/metabolismo , Ginsenosídeos/farmacologia , Animais , Antioxidantes/farmacologia , Senescência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Galactose/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Fatores de Transcrição/metabolismo
7.
An Acad Bras Cienc ; 92(1): e20191121, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428092

RESUMO

Cadmium, present in the environment, accumulates in different organs of animals and humans, and has deleterious effects on the kidney. In this study, we investigated the protective effects of the methanolic extract of Pleurotus ostreatus in comparison with silymarin on renal function in cadmium-intoxicated rats for five days. Rats intraperitoneally injected with cadmium chloride (1 mg/kg). These rats were treated with either P. ostreatus extract (200 mg/kg) or silymarin to investigate the protective effects of the extract. Cadmium treatment induced significant histopathological impairments and increased cadmium levels, DNA fragmentation, and renal oxidative stress. However, treatment with P. ostreatus extract or silymarin improved the pathology, reduced the level of cadmium in renal tissue, and restored DNA fragmentation. In addition, a significant reduction in lipid peroxidation and reactive oxygen species levels, and a significant increase in the levels of glutathione and catalase activity were observed. Thus, protective effects of P. ostreatus extract to its components. Chromatographic analysis of the P. ostreatus confirmed the presence of five phenolics (gallic acid, chlorogenic acid, catechin, propyl gallate, and cinnamic acid) that exhibit strong antioxidant properties as free radical scavengers. Therefore, our findings demonstrate that treatment with P. ostreatus extract protects against cadmium-induced nephrotoxicity in female rats.


Assuntos
Antioxidantes/farmacologia , Cloreto de Cádmio/toxicidade , Rim/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pleurotus/química , Silimarina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Cloreto de Cádmio/análise , Feminino , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos
8.
J Cancer Res Clin Oncol ; 146(7): 1801-1811, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32435894

RESUMO

PURPOSE: Oral mucositis is a debilitating inflammatory disorder observed in patients undergoing active cancer treatment, particularly cancer of the head and neck region. A key pathway believed to be involved in the pathogenesis of oral mucositis is the formation of reactive oxygen species (ROS). The identification of compounds that can inhibit this pathway may therefore be of benefit in treating this disorder. The kava plant (Piper methysticum) contains various constituents, including flavokawain A (FKA), flavokawain B (FKB), yangonin, methysticin and kavain. These constituents are known to be biologically active and possess anti-oxidative properties. This study therefore focused on examining these constituents for their effect on ROS formation in an in vitro oral mucositis model. METHODS: Cell proliferation was assessed in normal oral keratinocytes (OKF6) treated with and without kava constituents, namely FKA, FKB, yangonin, methysticin and kavain using an MTS in vitro assay. Oxidative stress was assessed by co-treating and pre-treating OKF6 cells with H2O2. The effects were quantified by analysis of ROS production, using a CM-H2DCFDA assay. RESULTS: Pre-treatment of cells for 24 h with 2.5 µg/ml kavain and 5 µg/ml FKA demonstrated a significant protective anti-oxidative effect. Similarly, FKB at a concentration of 2.5 µg/ml, demonstrated a trend of ROS reduction but was observed to be cytotoxic at concentrations greater than 5 µg/ml. Reduction in ROS production by methysticin and yangonin was compromised by their cell cytotoxicity. CONCLUSION: This was the first study to identify the anti-oxidative effects and safety of FKA and kavain with regard to oral keratinocytes, highlighting their potential use in the development of a preventative treatment for oral mucositis.


Assuntos
Kava/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Células Cultivadas , Humanos , Peróxido de Hidrogênio/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Substâncias Protetoras/química , Piranos/farmacologia , Pironas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Estomatite/tratamento farmacológico , Estomatite/etiologia
9.
Chemosphere ; 251: 126526, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32443237

RESUMO

Fine particle matter (PM2.5) has been extensively reported to contribute to the pathogenesis of pulmonary diseases. Recently, metformin has been reported to attenuate PM2.5 associated respiratory and cardiovascular injury, but the underling mechanism has not been discovered. Here, we performed comprehensively bioinformatics analysis and fully validation experiment to investigate the protection role of metformin and underling mechanism with RNAseq profile in GEO database. A combination of various bioinformatics tools including edgeR, principal component analysis (PCA), K-Means clustering, Gene Set Enrichment Analysis (GSEA), GO and KEGG enrichment were performed to identify the TLRs/MyD88/NF-κB axis functional as the key signaling transduction during PM2.5 associated toxicity. PM2.5 activated TLRs/MyD88/NF-κB pathway and resulted in significantly generation of IL-6, TNF-α, mitochondrial damage, decreasing of cell viability and increased LDH activity in RAW264.7 cells. Metformin significantly attenuated the production of IL-6, mitochondrial damage, cell viability and LDH activity by limiting TLRs/MyD88/NF-κB pathway. The siRNA against AMPKα2 or negative control were transfected to RAW264.7 cells to identify whether metformin protects PM2.5-induced cytotoxicity in an AMPKα2-dependent manner. Pretreatment with metformin significantly attenuated PM2.5 induced decreasing of cell viability and increased LDH activity, as well as inhibited the TLRs/MyD88/NF-κB pathway in both siControl or siAMPKα2 cells. Taken together, our results indicate that metformin protects against PM2.5-induced mitochondrial damage and cell cytotoxicity by inhibiting TLRs/MyD88/NF-κB signaling pathway in an AMPKα2 independent manner.


Assuntos
Poluentes Atmosféricos/toxicidade , Macrófagos/efeitos dos fármacos , Metformina/farmacologia , Material Particulado/toxicidade , Substâncias Protetoras/farmacologia , Receptores Toll-Like/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Humanos , Macrófagos/metabolismo , Camundongos , Células RAW 264.7 , Transdução de Sinais , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
Chemosphere ; 256: 127038, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32470728

RESUMO

Baicalein is a flavonoid that is widely found in plants. Studies have shown that baicalein has anti-inflammatory, anti-cancer, and liver-protective effects. However, the effects of baicalein on TAA-induced toxicity and the underlying molecular mechanisms in zebrafish larvae are still unknown. Here, we investigated the effects of baicalein on liver development and its anti-inflammatory effects in zebrafish larvae. The results showed that baicalein has significant anti-embryonic developmental toxicity and significant antioxidant and anti-inflammatory capabilities in TAA-induced zebrafish larvae and promotes liver development and cell proliferation, reduces the expression of apoptotic proteins, and induces the expression of anti-apoptotic proteins. At the molecular level of TAA-treated zebrafish larvae, there was a decrease in the relative expression levels of mRNAs of three subfamilies, P38, ERK1, and ERK2, of the MAPK-signaling pathway and of the products of peroxisome proliferator-activated receptor (PPAR)α. Compared with TAA-treated zebrafish larvae, zebrafish larvae treated with baicalein showed an increase in the relative expression levels of P38, ERK1, and ERK2 mRNAs and the downstream products of PPARα. When MAPK signal inhibitor (SB203580) was added, it was found that liver development was inhibited and baicalin had no protective effect on TAA induced hepatotoxicity in zebrafish larvae. The results showed baicalein can protect the zebrafish larvae against toxicity induced by TAA through MAPK signal pathway. Several molecular mechanisms discovered in this study may help in the development of new drugs.


Assuntos
Flavanonas/toxicidade , Tioacetamida/toxicidade , Peixe-Zebra/fisiologia , Animais , Anti-Inflamatórios/metabolismo , Antioxidantes/metabolismo , Flavonoides , Larva/efeitos dos fármacos , Fígado/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , PPAR alfa , Substâncias Protetoras/metabolismo , Transdução de Sinais/efeitos dos fármacos
12.
Chem Biol Interact ; 326: 109113, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32360496

RESUMO

Apple polyphenols (AP) have attracted much attention due to their various bioactivities. In this study, the protective effect of AP against chronic ethanol exposure-induced neural injury as well as the possible mechanisms were investigated. Body weight, daily average food intake and daily average fluid intake were measured and daily average ethanol consumption was calculated. The influences of AP on motor behavior and memory were detected by locomotor activity test, rotarod test, beam walking test, and Y maze test and novel object recognition test, respectively. The changes of blood ethanol concentration and the oxidative stress were also measured. AP improved chronic ethanol exposure-induced the inhibition of body weight and the decrease of daily average food intake, but did not influence the daily average fluid intake and the daily average ethanol intake, indicating that the improve effect of AP did not result from the decrease of ethanol intake. Motor activity and motor coordination were not influenced after chronic ethanol exposure though the blood ethanol concentration was higher than that in control group. AP improved significantly chronic ethanol-induced the memory impairment and the hippocampal CA1 neurons damage. Further studies found that AP decreased the contents of NO and MDA and increased the levels of T-AOC and GSH in the hippocampus of rats. These results suggest that AP exerts a protective effect against chronic ethanol-induced memory impairment through improving the oxidative stress in the hippocampus.


Assuntos
Etanol/efeitos adversos , Neurônios/efeitos dos fármacos , Polifenóis/farmacologia , Substâncias Protetoras/farmacologia , Animais , Glutationa/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Malus , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
14.
Chem Biol Interact ; 324: 109098, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32278740

RESUMO

This study evaluates the possible protective effects of gallic acid (GaA) and ferulic acid (FeA) against an experimentally induced liver fibrosis by thioacetamide (TAA) in rats. Animals were divided into: Control group, GaA group (20 mg/kg/day, p.o), FeA (20 mg/kg/day, p.o), TAA group (receiving 250 mg/kg twice/week, I.P), TAA + GaA group, TAA + FeA group (received the same previous doses) and TAA+silymarin group (received silymarin at 100 mg/kg/day+TAA as mentioned above). After 6 consecutive weeks, animals were sacrificed and the assessment of liver functions, oxidative stress biomarkers and histopathological examination of the liver tissues were performed. In addition, the effect on TGF-ß1/Smad3 signaling and the expression of miR-21, miR-30 and miR-200 were evaluated. The results showed that administration of GaA or FeA with TAA induced a significant reduction in serum ALT, AST and ALP activities and protected the integrity of liver tissues. Furthermore, they increased the activities of the hepatic antioxidant enzymes; superoxide dismutase and catalase while decreased malondialdehyde content to a normal level. The hepatic expression of TGF-ß1, phosphorylated and total Smad3 proteins were significantly decreased. In addition, miR-21 expression was downregulated while miR-30 and miR-200 expressions were upregulated by administration of gallic acid or ferulic acid. In conclusion, gallic and ferulic acids exhibit hepatoprotective and antioxidant effects against TAA-induced liver fibrosis in rats. These effects are mediated through inhibition of TGF-ß1/Smad3 signaling and differentially regulating the hepatic expression level of miR-21, miR-30 and miR-200.


Assuntos
Ácidos Cumáricos/uso terapêutico , Ácido Gálico/uso terapêutico , Expressão Gênica/efeitos dos fármacos , Cirrose Hepática/prevenção & controle , Substâncias Protetoras/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Regulação para Baixo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , MicroRNAs/metabolismo , Ratos Wistar , Proteína Smad3/metabolismo , Tioacetamida , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima
15.
Elife ; 92020 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-32250244

RESUMO

The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1-angiotensin II-angiotensin AT1 receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2-angiotensin(1-7)-angiotensin AT2 receptor and the ACE-2-angiotensin(1-7)-Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Pulmão/metabolismo , Pulmão/virologia , Pandemias , Pneumonia Viral/epidemiologia , Substâncias Protetoras/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos
16.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(2): 204-209, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32275007

RESUMO

OBJECTIVE: To investigate the role of Ribociclib in sepsis induced-acute kidney injury (AKI) and its possible mechanisms. METHODS: (1) Twenty adult male C57BL/6 mice were divided into sham operation group (Sham group; only open the abdomen without ligating or perforating the cecum, administered with sodium lactate buffer 12 hours before the sham operation), Ribociclib control group (administered with 150 mg/kg Ribociclib), cecal ligation and puncture (CLP) group (sepsis model induced by CLP; lactate buffer was given by intragastric administration 12 hours before CLP), and Ribociclib pretreatment group (administered with 150 mg/kg Ribociclib 12 hours before CLP) according to random number table, with 5 mice in each group. Kidneys were harvested 12 hours after the operation. Pathological changes in kidney were observed by hematoxylin-eosin (HE) staining. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in mice kidney homogenate were measured by enzyme linked immunosorbent assay (ELISA). Western Blot was used to detect the expression of cell cycle-related protein phosphorylate retinoblastoma protein (p-Rb), apoptosis-related protein Bcl-2 and Bax. (2) Mouse renal tubular epithelial (TCMK-1) cell line was used for in vitro experiment. The cells were divided into control group, Ribociclib group (treated with 5 µmol/L Ribociclib for 24 hours), lipopolysaccharide (LPS) group (treated with 200 mg/L LPS for 6 hours), Ribociclib+LPS group (replaced with the medium containing 5 µmol/L Ribociclib and 200 mg/L LPS for 6 hours after exposing with 5 µmol/L Ribociclib for 18 hours). Inflammatory cytokines in cell culture medium were detected by ELISA. The expression of p-Rb, Bcl-2 and Bax, autophagy-related proteins microtubule associated protein 1 light chain LC3b (LC3b II, LC3b I) and p62, phosphate protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR) were measured by Western Blot. RESULTS: (1) Animal experiments showed that, compared with the Sham group, the kidney tissue of mice were significantly damaged, the levels of TNF-α and IL-6 were increased, the expressions of p-Rb and Bcl-2/Bax ratio were decreased in kidney tissue in CLP group; but there was no significant difference in indexes between Ribociclib control group and Sham group. Compared with the CLP group, kidney injury in mice pretreated with Ribociclib was significantly ameliorated, the pathological score was significantly decreased (1.48±0.16 vs. 2.68±0.16, P < 0.01), the levels of TNF-α and IL-6 in kidney homogenate were significantly decreased [TNF-α (ng/g): 340.55±34.96 vs. 745.08±58.86, IL-6 (mg/g): 17.33±1.01 vs. 114.20±20.49, both P < 0.01], the expression of p-Rb was furtherly decreased (p-Rb/ß-tubulin: 0.14±0.01 vs. 0.73±0.06, P < 0.01), Bcl-2/Bax ratio was increased (0.89±0.06 vs. 0.62±0.10, P < 0.01). (2) In vitro experiments showed that, compared with the control group, the releases of TNF-α and IL-6 were increased, the expression of p-Rb was decreased, the ratios of Bcl-2/Bax and LC3b II/I were decreased, the expressions of p62, p-AKT and p-mTOR were increased in LPS group; the expression of p-Rb was decreased after Ribociclib treatment in TCMK-1 cells. Compared with the LPS group, TNF-α and IL-6 were decreased [TNF-α (ng/L): 2.73±0.23 vs. 4.96±0.10, IL-6 (ng/L): 36.05±5.83 vs. 53.78±24.08, both P < 0.01], the expression of p-Rb was furtherly decreased (p-Rb/ß-tubulin: 0.25±0.05 vs. 0.65±0.05, P < 0.01), the ratios of Bcl-2/Bax and LC3b II/I were increased (Bcl-2/Bax: 1.01±0.07 vs. 0.73±0.05, LC3b II/I: 2.08±0.31 vs. 1.04±0.01, both P < 0.05), the expressions of p62, p-AKT and p-mTOR were decreased (p62/ß-tubulin: 0.59±0.01 vs. 1.09±0.08, p-AKT/ß-tubulin: 0.61±0.03 vs. 1.20±0.06, p-mTOR/ß-tubulin: 0.50±0.05 vs. 1.15±0.08, all P < 0.01) in the Ribociclib+LPS group. CONCLUSIONS: Ribociclib pretreatment ameliorated sepsis-induced AKI and AKT/mTOR pathway may be involved in the protective role of Ribociclib on kidney.


Assuntos
Lesão Renal Aguda , Aminopiridinas/uso terapêutico , Substâncias Protetoras/uso terapêutico , Purinas/uso terapêutico , Sepse , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa
17.
Life Sci ; 251: 117645, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32268154

RESUMO

Acute pancreatitis (AP) is a noninfectious inflammatory disease with high morbidity and mortality, which is characterized by severe inflammation and tissue necrosis. Cordycepin (CRD), derived from Cordyceps militaris, possesses anti-inflammatory effects and immunomodulation properties. Here, we investigated the protective effects of CRD on pancreatic injury and clarified potential mechanisms in AP model. There were established caerulein-induced AP and CRD pretreatment models in vivo and in vitro, as showed by serum enzymes, histopathological alterations and pro-inflammatory cytokines. Pretreatment with CRD notably downregulated the serum amylase and lipase levels and apparently reduced pancreatic histopathological alterations in AP mice. Meanwhile, the MPO staining confirmed that CRD pretreatment modulated the infiltration of neutrophils in AP mice. Furthermore, CRD markedly decreased the levels of pro-inflammatory factors (IL-6, IL-1ß, and TNF-α) though inhibiting the activation of nuclear factor-κB (NF-κB) and NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome in AP mice. In pancreatic acinar cancer cell 266-6, CRD pretreatment decreased cholecystokinin(CCK)-induced inflammatory response was consistent with those in vivo. Mechanistically, CRD was also revealed to activate activated protein kinase (AMPK) and attenuated inflammation both in vivo and in vitro. On the whole, this study indicated that CRD protects mice from pancreatic inflammatory process and damage by suppressed NF-κB and NLRP3 inflammasome activation via AMPK, which probably contributed to the potential therapy for AP.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Desoxiadenosinas/farmacologia , Inflamassomos/metabolismo , Inflamação/prevenção & controle , Pancreatite/prevenção & controle , Doença Aguda , Animais , Biomarcadores/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Substâncias Protetoras/farmacologia
18.
Life Sci ; 253: 117626, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32247002

RESUMO

AIMS: Postoperative cognitive dysfunction (POCD) is a common postoperative complication that is associated with increased morbidity and mortality. However, the mechanism of pathogenesis of POCD still remains largely unknown. The aim of the study was to investigate the function and mechanism of lncRNA PCAI in POCD. MATERIALS AND METHODS: Knockdown and overexpression studies were performed to analyze the function of lncRNA PCAI in cultured BV-2 cell lines treated with LPS to mimic the neuroinflammation. Real-time PCR, western blot, ELISA were used to determine the expression level of inflammation markers. Rescue experiment was performed to prove the relationship between PCAI and SUZ12. RESULTS: We found that the expression of lncRNA PCAI was decreased with the increasing concentrations of LPS. Knockdown of lncRNA PCAI inhibited the cell death rates and attenuated the cell inflammation via ELISA and real-time PCR. Besides, downregulated of lncRNA PCAI can protect the mitochondrial function via membrane potential assay. Overexpression of lncRNA PCAI can promote the cell death and inflammation response induced by LPS. We also provided mechanism study about lncRNA PCAI that negatively regulating SUZ12. Rescue experiment also verified the results. CONCLUSION: We performed comprehensive study of functional analysis of lncRNA PCAI in POCD and proved its mechanism, which negatively regulate SUZ12. Our study provided new clues for the clinical intervention and targets for POCD.


Assuntos
Disfunção Cognitiva/etiologia , Hipocampo/metabolismo , Inflamação/metabolismo , Complicações Cognitivas Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , RNA Longo não Codificante/genética , Animais , Linhagem Celular , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Inflamação/patologia , Camundongos , Membranas Mitocondriais/metabolismo , Complexo Repressor Polycomb 2/genética , Substâncias Protetoras/metabolismo , Substâncias Protetoras/farmacologia
19.
Nat Commun ; 11(1): 1608, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32231209

RESUMO

The emerging resistance of crop pathogens to fungicides poses a challenge to food security and compels discovery of new antifungal compounds. Here, we show that mono-alkyl lipophilic cations (MALCs) inhibit oxidative phosphorylation by affecting NADH oxidation in the plant pathogens Zymoseptoria tritici, Ustilago maydis and Magnaporthe oryzae. One of these MALCs, consisting of a dimethylsulfonium moiety and a long alkyl chain (C18-SMe2+), also induces production of reactive oxygen species at the level of respiratory complex I, thus triggering fungal apoptosis. In addition, C18-SMe2+ activates innate plant defense. This multiple activity effectively protects cereals against Septoria tritici blotch and rice blast disease. C18-SMe2+ has low toxicity in Daphnia magna, and is not mutagenic or phytotoxic. Thus, MALCs hold potential as effective and non-toxic crop fungicides.


Assuntos
Cátions/farmacologia , Produtos Agrícolas/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Doenças das Plantas/prevenção & controle , Substâncias Protetoras/farmacologia , Animais , Ascomicetos/efeitos dos fármacos , Cátions/química , Daphnia/efeitos dos fármacos , Descoberta de Drogas , Grão Comestível/microbiologia , Fibroblastos/efeitos dos fármacos , Fungicidas Industriais/química , Humanos , Mitocôndrias/efeitos dos fármacos , Oryza/microbiologia , Doenças das Plantas/microbiologia , Substâncias Protetoras/química , Triticum/microbiologia , Ustilago/efeitos dos fármacos
20.
Food Chem ; 322: 126742, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32305872

RESUMO

Almond hulls, the main by-product of almond production, are considered a valuable source of bioactive phenolic compounds. This study aimed to characterize the phenolic composition, bioavailability of the phenolic-rich extracts from almond hulls (PEAH), and their protective effect on oxidative stressed Caco-2 cells induced by tert-butylhydroperoxide (t-BOOH). The ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) analysis detected 11 phenolic compounds in the PEAH with high total phenolic content and antioxidant activity. Oxidative Caco-2 cell damage was reduced by PEAH, especially at 5 µg/mL, through scavenging reactive oxygen species (ROS), modulating the cellular endogenous antioxidant system and cell redox at a predictable status. Also, in vitro digestion influenced the phenolic compounds' composition and antioxidant power of PEAH. These results suggested that almond hulls, rich in phenolic compounds, can meliorate the oxidative stressed Caco-2 cells and restore its impaired redox balance, and ultimately improve health benefits.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Fenóis/química , Extratos Vegetais/química , Substâncias Protetoras/farmacologia , Prunus dulcis/química , Antioxidantes/química , Disponibilidade Biológica , Células CACO-2 , Cromatografia Líquida de Alta Pressão , Análise Discriminante , Meia-Vida , Humanos , Análise dos Mínimos Quadrados , Espectrometria de Massas , Oxirredução , Fenóis/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacocinética , Prunus dulcis/metabolismo , Espécies Reativas de Oxigênio/química , terc-Butil Hidroperóxido/toxicidade
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