Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.851
Filtrar
1.
Int J Nanomedicine ; 16: 2461-2475, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33814910

RESUMEN

Aim: To explore the effects of Radix Sophorae Flavescentis carbonisata-based carbon dots (RSFC-CDs) on an ethanol-induced acute gastric ulcer rat model. Methods: The structure, optical properties, functional groups and elemental composition of RSFC-CDs synthesized by one-step pyrolysis were characterized. The gastric protective effects of RSFC-CDs were evaluated and confirmed by applying a rat model of ethanol-induced acute gastric ulcers. The underlying mechanisms were investigated through the nuclear factor-kappa B (NF-κB) signalling pathway and oxidative stress. Results: RSFC-CDs with a diameter ranging from 2-3 nm mainly showed gastric protective effects by reducing the levels of NF-κB, tumour necrosis factor-α (TNF-α), interleukin (IL)-6, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione (GSH), malondialdehyde (MDA) and inducible nitric oxide synthase (iNOS) to inhibit ethanol-induced inflammation and oxidative stress. Conclusion: RSFC-CDs have anti-inflammatory and anti-oxidative effects, making them promising for application in ethanol-induced gastric injury.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Carbono/química , Medicamentos Herbarios Chinos/uso terapéutico , Sustancias Protectoras/uso terapéutico , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Enfermedad Aguda , Animales , Antiinflamatorios/farmacología , Antioxidantes/farmacología , Regulación hacia Abajo/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Etanol/efectos adversos , Interleucina-6/metabolismo , Masculino , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , Espectroscopía de Fotoelectrones , Sustancias Protectoras/farmacología , Ratas Sprague-Dawley , Úlcera Gástrica/patología , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacos
2.
Int J Mol Sci ; 22(5)2021 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-33670975

RESUMEN

Excessive intake of fructose results in metabolic syndrome (MS) and kidney damage, partly mediated by its metabolism by fructokinase-C or ketohexokinase-C (KHK-C). Osthol has antioxidant properties, is capable of regulating adipogenesis, and inhibits KHK-C activity. Here, we examined the potential protective role of osthol in the development of kidney disease induced by a Western (high-fat/high-sugar) diet. Control rats fed with a high-fat/high-sugar diet were compared with two groups that also received two different doses of osthol (30 mg/kg/d or 40 mg/kg/d body weight BW). A fourth group served as a normal control and received regular chow. At the end of the follow-up, kidney function, metabolic markers, oxidative stress, and lipogenic enzymes were evaluated. The Western diet induced MS (hypertension, hyperglycemia, hypertriglyceridemia, obesity, hyperuricemia), a fall in the glomerular filtration rate, renal tubular damage, and increased oxidative stress in the kidney cortex, with increased expression of lipogenic enzymes and increased kidney KHK expression. Osthol treatment prevented the development of MS and ameliorated kidney damage by inhibiting KHK activity, preventing oxidative stress via nuclear factor erythroid 2-related factor (Nrf2) activation, and reducing renal lipotoxicity. These data suggest that the nutraceutical osthol might be an ancillary therapy to slow the progression of MS and kidney damage induced by a Western diet.


Asunto(s)
Cumarinas/farmacología , Dieta Occidental/efectos adversos , Fructoquinasas/antagonistas & inhibidores , Enfermedades Renales/prevención & control , Síndrome Metabólico/prevención & control , Animales , Cumarinas/uso terapéutico , Dieta de Carga de Carbohidratos/efectos adversos , Dieta Alta en Grasa/efectos adversos , Fructoquinasas/metabolismo , Fructosa/metabolismo , Enfermedades Renales/etiología , Enfermedades Renales/metabolismo , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Ratas , Ratas Wistar
3.
Int J Mol Sci ; 22(4)2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33669855

RESUMEN

Colitis is a multifactorial disorder that mostly occurs in the gastrointestinal tract. Despite improvements in mucosal inflammation research, little is known regarding the small bioactive molecules that are beneficial for regulating T cells and colon cell activity. 6,7,4'-trihydroxyflavanone (THF) is a flavanone that possesses anti-osteoclastogenesis activity and exerts protective effects against methamphetamine-induced immunotoxicity. Whether THF mitigates intestinal inflammation by regulating T cells and colon cell activity remains unknown. In the present study, Jurkat and HT-29 cells were used for in vitro experiments, and dextran sulfate sodium (DSS)-induced colitis model in mice was used for in vivo experiment. We observed that THF did not have a negative effect on the viability of Jurkat and HT-29 cells. Quantitative PCR and Western blot analysis revealed that THF regulates the activity of Jurkat cells and HT-29 cells via the NFκB and MAPK pathways under stimulated conditions. In the DSS-induced colitis model, oral administration of THF attenuated the manifestations of DSS-induced colitis, including a reduction in body weight, shrinkage of the colon, and enhanced expression of pro-inflammatory cytokines in the colon and mesenteric lymph nodes. These data suggest that THF alleviates DSS-induced colitis by modulating the activity of T cells and colon cells in vivo.


Asunto(s)
Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colon/inmunología , Colon/patología , Flavanonas/uso terapéutico , Sustancias Protectoras/uso terapéutico , Linfocitos T/inmunología , Administración Oral , Animales , Peso Corporal/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colitis/inmunología , Citocinas/metabolismo , Sulfato de Dextran , Modelos Animales de Enfermedad , Femenino , Flavanonas/administración & dosificación , Flavanonas/química , Flavanonas/farmacología , Células HT29 , Humanos , Inflamación/patología , Intestinos/patología , Células Jurkat , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos C57BL , Sustancias Protectoras/farmacología , Linfocitos T/efectos de los fármacos , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th17/efectos de los fármacos , Células Th17/inmunología , Factor de Transcripción ReIA/metabolismo
4.
Cell Prolif ; 54(4): e13021, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33751704

RESUMEN

Although the liver is the only organ with regenerative capacity, various injury factors induce irreversible liver dysfunction and end-stage liver disease. Liver resection and liver transplantation (LT) are effective treatments for individuals with liver failure, liver cirrhosis and liver cancers. The remnant or transplanted liver tissues will undergo hepatic ischaemia/reperfusion (IR), which leads to oxidative stress, inflammation, immune injury and liver damage. Moreover, systemic ischaemia induced by trauma, stroke, myocardial ischaemia, haemorrhagic shock and other injury factors also induces liver ischaemia/reperfusion injury (IRI) in individuals. Hepatic IRI can be divided into warm IRI, which is induced by liver surgery and systemic ischaemia, and cold IRI, which is induced by LT. Multiple studies have shown that melatonin (MT) acts as an endogenous free radical scavenger with antioxidant capacity and is also able to attenuate hepatic IRI via its anti-inflammatory and antiapoptotic capacities. In this review, we discuss the potential mechanisms and current strategies of MT administration in liver surgery for protecting against warm or cold hepatic IRI. We highlight strategies to improve the efficacy and safety of MT for attenuating hepatic IRI in different conditions. After the potential mechanisms underlying the interactions between MT and other important cellular processes during hepatic IR are clarified, more opportunities will be available to use MT to treat liver diseases in the future.


Asunto(s)
Melatonina/uso terapéutico , Daño por Reperfusión/prevención & control , Antioxidantes/química , Apoptosis/efectos de los fármacos , Rechazo de Injerto/patología , Rechazo de Injerto/prevención & control , Humanos , Hígado/metabolismo , Hígado/patología , Melatonina/química , Melatonina/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Daño por Reperfusión/patología , Transducción de Señal/efectos de los fármacos
5.
Eur Rev Med Pharmacol Sci ; 25(4): 2131-2145, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33660833

RESUMEN

The world is currently facing the COVID-19 pandemic, caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Due to a lack of specific treatment and prophylaxis, protective health measures that can reduce infection severity and COVID-19 mortality are urgently required. Clinical and epidemiological studies have shown that vitamin D deficiency can be linked to an increased risk of viral infection, including COVID-19. Therefore, in this review, we looked at various possible roles of vitamin D in reducing the risk of COVID-19 infection and severity. We describe in this article that individuals at high risk of vitamin D deficiency should consider taking vitamin D supplements to keep optimal concentrations. Moreover, we discuss different possible mechanisms by which vitamin D can efficiently reduce the risk of infections through modulation of innate and adaptive immunity against various types of infections. It is advisable to perform further studies addressing the observed influence of vitamin D levels to reduce the risk of COVID-19 infection and mortality.


Asunto(s)
/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Deficiencia de Vitamina D/prevención & control , Vitamina D/uso terapéutico , Inmunidad Adaptativa/efectos de los fármacos , Efecto Espectador , /mortalidad , Suplementos Dietéticos , Humanos , Inmunidad Innata/efectos de los fármacos , Sustancias Protectoras/administración & dosificación , Índice de Severidad de la Enfermedad , Vitamina D/administración & dosificación , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/inmunología
6.
Int J Mol Sci ; 22(4)2021 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-33562294

RESUMEN

Heart failure (HF) is a leading cause of death in the United States, with a 5-year mortality rate of 50% despite modern pharmacological therapies. Plant-based diets are comprised of a diverse polyphenol profile, which lends to their association with reduced cardiovascular disease risk. Whether a polyphenol-rich diet can slow the progression of or reverse HF in humans is not known. To date, in vitro and in vivo studies have reported on the protective role of polyphenols in HF. In this review, we will discuss the major mechanisms by which polyphenols mitigate HF in vitro and in vivo, including (1) reduced cardiac inflammation and oxidative stress, (2) reduced mitochondrial dysfunction, (3) improved Ca2+ homeostasis, (4) increased survival signaling, and (5) increased sirtuin 1 activity.


Asunto(s)
Insuficiencia Cardíaca/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Polifenoles/uso terapéutico , Sustancias Protectoras/uso terapéutico , Animales , Insuficiencia Cardíaca/metabolismo , Humanos , Inflamación/metabolismo
7.
Eur J Pharmacol ; 898: 173934, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33609563

RESUMEN

Metformin is the most commonly prescribed oral antidiabetic medication. Direct/indirect activation of Adenosine Monophosphate-activated protein kinase (AMPK) and non-AMPK pathways, amongst others, are deemed to explain the molecular mechanisms of action of metformin. Metformin is an established insulin receptor sensitising antihyperglycemic agent, is highly affordable, and has superior safety and efficacy profiles. Emerging experimental and clinical evidence suggests that metformin has pleiotropic non-glycemic effects. Metformin appears to have weight stabilising, renoprotective, neuroprotective, cardio-vascular protective, and antineoplastic effects and mitigates polycystic ovarian syndrome. Anti-inflammatory and antioxidant effects of metformin seem to qualify it as an adjunct therapy in treating infectious diseases such as tuberculosis, viral hepatitis, and the current novel Covid-19 infections. So far, metformin is the only prescription medicine relevant to the emerging field of senotherapeutics. Non-glycemic effects of metformin favourable to its repurposing in therapeutic use are hereby discussed.


Asunto(s)
Antiinfecciosos/uso terapéutico , Antineoplásicos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Factores Inmunológicos/uso terapéutico , Metformina/uso terapéutico , Sustancias Protectoras/uso terapéutico , Animales , Antiinfecciosos/efectos adversos , Antineoplásicos/efectos adversos , /epidemiología , Enfermedades Cardiovasculares/prevención & control , Femenino , Humanos , Hipoglucemiantes/efectos adversos , Factores Inmunológicos/efectos adversos , Enfermedades Renales/prevención & control , Síndrome Metabólico/tratamiento farmacológico , Metformina/efectos adversos , Obesidad/tratamiento farmacológico , Pandemias , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Sustancias Protectoras/efectos adversos
8.
Int J Biol Macromol ; 171: 398-413, 2021 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-33422516

RESUMEN

Diatoms are ubiquitous, biologically widespread, and have global significance due to their unique silica cell wall composition and noteworthy applied aspects. Diatoms are being extensively exploited for environmental monitoring, reconstruction, and stratigraphic correlation. However, considering all the rich elements of diatoms biology, the current literature lacks sufficient information on the therapeutic attributes and applied aspects of biological macromolecules from diatoms, hampering added advances in all aspects of diatom biology. Diatoms offer numerous high-value compounds, such as fatty acids, polysaccharides, polypeptides, pigments, and polyphenols. Diatoms with a high content of PUFA's are targets of transformation into high-value products through microalgal technologies due to their wide application and growing market as nutraceuticals and food supplements. Diatoms are renewable biomaterial, which can be used to develop drug delivery systems due to biocompatibility, surface area, cost-effective ratio, and ease in surface modifications. Innovative approaches are needed to envisage cost-effective ways for the isolation of bioactive compounds, enhance productivity, and elucidate the detailed mechanism of action. This review spotlights the notable applications of diatoms and their biologically active constituents, such as fucoxanthin and omega 3 fatty acids, among others with unique structural and functional entities.


Asunto(s)
Diatomeas/química , Sustancias Macromoleculares/uso terapéutico , Suplementos Dietéticos , Sistemas de Liberación de Medicamentos , Ácidos Grasos/aislamiento & purificación , Ácidos Grasos/uso terapéutico , Humanos , Sustancias Macromoleculares/economía , Sustancias Macromoleculares/aislamiento & purificación , Péptidos/aislamiento & purificación , Péptidos/uso terapéutico , Polifenoles/aislamiento & purificación , Polifenoles/uso terapéutico , Polisacáridos/aislamiento & purificación , Polisacáridos/uso terapéutico , Sustancias Protectoras/uso terapéutico , Esteroles/aislamiento & purificación , Esteroles/uso terapéutico , Xantófilas/aislamiento & purificación , Xantófilas/uso terapéutico
9.
Molecules ; 26(2)2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33467396

RESUMEN

Inflammatory bowel disease (IBD) is a non-communicable disease characterized by a chronic inflammatory process of the gut and categorized into Crohn's disease and ulcerative colitis, both currently without definitive pharmacological treatment and cure. The unclear etiology of IBD is a limiting factor for the development of new drugs and explains the high frequency of refractory patients to current drugs, which are also related to various adverse effects, mainly after long-term use. Dissatisfaction with current therapies has promoted an increased interest in new pharmacological approaches using natural products. Coumarins comprise a large class of natural phenolic compounds found in fungi, bacteria, and plants. Coumarin and its derivatives have been reported as antioxidant and anti-inflammatory compounds, potentially useful as complementary therapy of the IBD. These compounds produce protective effects in intestinal inflammation through different mechanisms and signaling pathways, mainly modulating immune and inflammatory responses, and protecting against oxidative stress, a central factor for IBD development. In this review, we described the main coumarin derivatives reported as intestinal anti-inflammatory products and its available pharmacodynamic data that support the protective effects of these products in the acute and subchronic phase of intestinal inflammation.


Asunto(s)
Cumarinas/uso terapéutico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Animales , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Cumarinas/farmacología , Humanos , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico
10.
RMD Open ; 7(1)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33455920

RESUMEN

BACKGROUND: The recent outbreak of COVID-19 has raised concerns in the rheumatology community about the management of immunosuppressed patients diagnosed with inflammatory rheumatic diseases. It is not clear whether the use of biological agents may suppose a risk or protection against SARS-CoV-2 infection; however, it has been suggested that severe respiratory forms of COVID-19 occur as a result of exacerbated inflammation status and cytokine production. This prompted the use of interleukin 6 (IL-6) (tocilizumab and sarilumab) and IL-1 inhibitors (anakinra) in severe COVID-19 disease and more recently JAK1/2 inhibitor (baricitinib). Therefore, patients with rheumatic diseases provide a great opportunity to learn about the use of biological agents as protective drugs against SARS-CoV-2. OBJECTIVES: To estimate COVID-19 infection rate in patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) for inflammatory rheumatic diseases (RMD), determine the influence of biological agents treatment as risk or protective factors and study the prognosis of patients with rheumatic diseases receiving biological agents compared to the general population in a third-level hospital setting in León, Spain. METHODS: We performed a retrospective observational study including patients seen at our rheumatology department who received bDMARDs for rheumatic diseases between December 1st 2019 and December 1st 2020, and analysed COVID-19 infection rate. All patients who attended our rheumatology outpatient clinic with diagnosis of inflammatory rheumatic disease receiving treatment with biological agents were included. Main variable was the hospital admission related to COVID-19. The covariates were age, sex, comorbidities, biological agent, duration of treatment, mean dose of glucocorticoids and need for intensive care unit . We performed an univariate and multivariate logistic regression models to assess risk factors of COVID-19 infection. RESULTS: There were a total of 4464 patients with COVID-19 requiring hospitalisation. 40 patients out of a total of 820 patients with rheumatic diseases (4.8%) receiving bDMARDs contracted COVID-19 and 4 required hospital care. Crude incidence rate of COVID-19 requiring hospital care among the general population was 3.6%, and it was 0.89% among the group with underlying rheumatic diseases. 90% of patients receiving bDMARDS with COVID-19 did not require hospitalisation. Out of the 4464 patients, 869 patients died, 2 of which received treatment with biological agents. Patients with rheumatic diseases who tested positive for COVID-19 were older (female: median age 60.8 IQR 46-74; male: median age 61.9 IQR 52-70.3) than those who were negative for COVID-19 (female: median age 58.3 IQR 48-69; male: median age 56.2 IQR 47-66), more likely to have hypertension (45% vs 26%, OR 2.25 (CI 1.18-4.27),p 0.02), cardiovascular disease (23 % vs 9.6%, OR 2.73 (1.25-5.95), p 0.02), be smokers (13% vs 4.6%, OR 2.95 (CI 1.09-7.98), p 0.04), receiving treatment with rituximab (20% vs 8%, 2.28 (CI 1.24-6.32), p 0.02) and a higher dose of glucocorticoids (OR 2.5 (1.3-10.33, p 0.02) and were less likely to be receiving treatment with IL-6 inhibitors (2.5% vs 14%, OR 0.16, (CI 0.10-0.97, p 0.03). When exploring the effect of the rest of the therapies between groups (affected patients vs unaffected), we found no significant differences in bDMARD proportions. IL-1 inhibitors, IL-6 inhibitors, JAK inhibitors and belimumab-treated patients showed the lowest incidence of COVID-19 among adult patients with rheumatic diseases. We found no differences in sex or rheumatological disease between patients who tested positive for COVID-19 and patients who tested negative. CONCLUSIONS: Overall, the use of biological disease-modifying antirheumatic drugs (bDMARDs) does not associate with severe manifestations of COVID-19. Patients with rheumatic disease diagnosed with COVID-19 were more likely to be receiving a higher dose of glucocorticoids and treatment with rituximab. IL-6 inhibitors may have a protective effect.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Factores Biológicos/uso terapéutico , Brotes de Enfermedades , Glucocorticoides/uso terapéutico , Sustancias Protectoras/uso terapéutico , Enfermedades Reumáticas/tratamiento farmacológico , Rituximab/uso terapéutico , /aislamiento & purificación , Anciano , Anticuerpos Monoclonales Humanizados/farmacología , Femenino , Humanos , Interleucina-6/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , /inmunología , España/epidemiología , Resultado del Tratamiento
11.
Chem Biol Interact ; 335: 109332, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33387473

RESUMEN

Renal fibrosis is a major cause of renal failure in diabetic nephropathy. Tropisetron is an antagonist of the 5HT3 receptor that exhibits anti-fibrosis effects. The present research aimed to investigate the protected role of tropisetron against renal fibrosis of diabetic nephropathy and its molecular mechanisms. For this purpose, male Wistar rats were allocated into 5 groups of control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). After induction of type 1 diabetes with a single injection of STZ, tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) were given to the rats daily by intraperitoneal injection for 2 weeks. The obtained data revealed that the treatment of diabetic rats with tropisetron led to a significant decrease in the elevated blood glucose, serum cystatin c, and urinary total protein (UTP) level, indicating the improvement of the impaired kidney function. Moreover, the results of Masson's trichrome staining showed that fibrosis attenuated in the kidney of diabetic rats after tropisetron treatment. RT-PCR and Western blotting revealed that TGF-ß1, the apoptotic mediator, and p53 were considerably declined in the kidney of diabetic rats in response to tropisetron treatment. Meanwhile, the expressions of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) were increased. These notable effects were equipotent with glibenclamide, as a standard drug, suggesting that tropisetron can alleviate renal fibrosis in diabetic nephropathy. Our data indicate that tropisetron could improve kidney function and attenuate renal fibrosis through regulation of TGF-ß1, p53, and expression of extracellular matrix metalloproteinases.


Asunto(s)
Nefropatías Diabéticas/tratamiento farmacológico , Fibrosis/tratamiento farmacológico , Riñón/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Tropisetrón/uso terapéutico , Animales , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/patología , Fibrosis/patología , Fibrosis/prevención & control , Glucosa/metabolismo , Riñón/patología , Masculino , Proteínas/metabolismo , Ratas Wistar , Estreptozocina
12.
Life Sci ; 269: 119013, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33417950

RESUMEN

OBJECTIVE: To investigate the protective efficacies and potent mechanisms of combination therapy with semaglutide and rosiglitazone (RSG) on the high-glucose incubated human ARPE-19 cells and diabetic retinopathy (DR) model rats. MAIN METHODS: The CCK-8 methods were used to evaluate the protective effects of semaglutide and RSG alone or combination on the cell viability of high-glucose treated ARPE-19 cells. After the DR rat model was established, the effects of combined treatment on general indexes, retinal morphological changes, retinal Müller cells as well as PI3K/Akt/MTOR related factors of DR model rats were investigated. RESULTS: The CCK-8 assay showed obviously enhanced protective efficacies of combination therapy with semaglutide and RSG on the ARPE-19 with oxidative stress induced by high-glucose with combination index all below 1.5 demonstrating obvious synergistic effects. Combined incubation could also effectively decrease the expression of inflammatory factors, including TNF-α, IL-1ß, IL-6, and the increase of ROS content in ARPE cell culture supernatant induced by high-glucose. Combined use of the antioxidant, PI3K/Akt and mTOR inhibitors, we further demonstrated that combined incubation of semaglutide and RSG could effectively by reduce high glucose-induced inflammatory injury inhibiting ROS/PI3K/Akt/mTOR signaling. Furthermore, chronic combination treatment effectively improved the histopathological characteristics and down-regulated the GFAP expression in Müller cells as well as PI3K/Akt/MTOR signaling pathway-related factors in retina which was better than any monomer treatment group. CONCLUSIONS: Combined semaglutide with RSG exhibited synergistically protective efficacies on retinal cells by decreasing the GFAP expression, inhibiting oxidative stress and PI3K/Akt/MTOR signaling-transduction in DR model rats.


Asunto(s)
Retinopatía Diabética/tratamiento farmacológico , Péptidos Similares al Glucagón/uso terapéutico , Rosiglitazona/uso terapéutico , Animales , Antioxidantes/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Quimioterapia Combinada , Células Ependimogliales/efectos de los fármacos , Células Ependimogliales/metabolismo , Células Ependimogliales/patología , Proteína Ácida Fibrilar de la Glía/metabolismo , Péptidos Similares al Glucagón/farmacología , Humanos , Inflamación/patología , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Rosiglitazona/farmacología , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo
13.
PLoS One ; 15(9): e0238163, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32881885

RESUMEN

OBJECTIVE: We evaluated the effects of grape juice (Vitis labrusca L.) on dyslipidemia, resistance to insulin, and left ventricular hypertrophy (LVH) in mice homozygous for the absence of the LDL receptor gene (LDLr -/-) under a hyperlipidemic diet. METHODOLOGY: We divided 30 male mice (3 months old) into three groups (n = 10); the HL group was fed a high-fat diet, the HLU group received a high-fat diet and 2 g/kg/day of grape juice, and the HLS group was fed a high-fat diet and simvastatin (20 mg/kg/day). We assessed the blood pressure profile of the mice. We also determined the levels of C-reactive protein (CRP) and lipid profile, glycemic and insulinemic profiles, and calculated the HOMA-IR. Cardiomyocyte hypertrophy, interstitial collagen deposit, and the expression of CD40 ligand (CD40L) and metalloproteinases 2 and 9 were assessed immunohistologically. RESULTS: After 60 days, the mice treated with grape juice showed similar results as those of the group treated with simvastatin. The use of grape fruit attenuated dyslipidemia and insulin resistance and significantly increased the levels of high cholesterol density lipoproteins (HDLc). The antioxidant potential of phenolic compounds associated with the increase in HDLc levels in the mice of the HLU group prevented the development of LVH and arterial hypertension since it inhibited the inflammatory response induced by the CD40 pathway and its ligand CD40L. Consequently, there was a lower expression of MMP-2 and MMP-9 and lower serum levels of CRP. CONCLUSION: Grape juice has a hypolipidemic and cardiac protective potential, presenting a similar effect as that of simvastatin through a direct antioxidant action of phenolic compounds, or indirectly, via antioxidant action and anti-inflammatory activity of the HDLc. These results suggest that grape juice is a functional food possessing a high potential to prevent cardiovascular diseases.


Asunto(s)
Dislipidemias/patología , Jugos de Frutas y Vegetales , Hipertrofia Ventricular Izquierda/prevención & control , Vitis/química , Animales , Presión Sanguínea/efectos de los fármacos , Proteína C-Reactiva/análisis , Ligando de CD40/genética , Ligando de CD40/metabolismo , Colágeno/metabolismo , Dieta Alta en Grasa , Dislipidemias/tratamiento farmacológico , Jugos de Frutas y Vegetales/análisis , Ventrículos Cardíacos/patología , Hipertrofia Ventricular Izquierda/patología , Masculino , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Sustancias Protectoras/química , Sustancias Protectoras/uso terapéutico , Receptores de LDL/deficiencia , Receptores de LDL/genética , Simvastatina/uso terapéutico , Vitis/metabolismo
14.
PLoS One ; 15(8): e0236879, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32790676

RESUMEN

Benign prostatic hyperplasia (BPH) is a progressive pathological condition associated with proliferation of prostatic tissues, prostate enlargement, and lower-urinary tract symptoms. However, the mechanism underlying the pathogenesis of BPH is unclear. The aim of this study was to investigate the protective effects of a combination of Stauntonia hexaphylla and Cornus officinalis (SC extract) on a testosterone propionate (TP)-induced BPH model. The effect of SC extract was examined in a TP-induced human prostate adenocarcinoma cell line. Male Sprague-Dawley rats were randomly divided into 5 groups (n = 6) for in vivo experiments. To induce BPH, all rats, except those in the control group, were administered daily with subcutaneous injections of TP (5 mg/kg) and orally treated with appropriate phosphate buffered saline/drugs (finasteride/saw palmetto/SC extract) for 4 consecutive weeks. SC extract significantly downregulated the androgen receptor (AR), prostate specific antigen (PSA), and 5α-reductase type 2 in TP-induced BPH in vitro. In in vivo experiments, SC extract significantly reduced prostate weight, size, serum testosterone, and dihydrotestosterone (DHT) levels. Histologically, SC extract markedly recovered TP-induced abnormalities and reduced prostatic hyperplasia, thereby improving the histo-architecture of TP-induced BPH rats. SC extract also significantly downregulated AR and PSA expression, as assayed using immunoblotting. Immunostaining revealed that SC extract markedly reduced the 5α-reductase type 2 and significantly downregulated the expression of proliferating cell nuclear antigen. In addition, immunoblotting of B-cell lymphoma 2 (Bcl-2) family proteins indicated that SC extract significantly downregulated anti-apoptotic Bcl-2 and markedly upregulated pro-apoptotic B cell lymphoma-associated X (Bax) expression. Furthermore, SC treatment significantly decreased the Bcl-2/Bax ratio, indicating induced prostate cell apoptosis in TP-induced BPH rats. Thus, our findings demonstrated that SC extract protects against BPH by inhibiting 5α-reductase type 2 and inducing prostate cell apoptosis. Therefore, SC extract might be useful in the clinical treatment of BPH.


Asunto(s)
Apoptosis/efectos de los fármacos , Colestenona 5 alfa-Reductasa/química , Extractos Vegetales/farmacología , Hiperplasia Prostática/prevención & control , Sustancias Protectoras/uso terapéutico , Inhibidores de 5-alfa-Reductasa/química , Inhibidores de 5-alfa-Reductasa/farmacología , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colestenona 5 alfa-Reductasa/metabolismo , Cornus/química , Cornus/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Humanos , Masculino , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Antígeno Prostático Específico/sangre , Hiperplasia Prostática/etiología , Sustancias Protectoras/farmacología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ranunculales/química , Ranunculales/metabolismo , Ratas , Ratas Sprague-Dawley , Propionato de Testosterona/efectos adversos
15.
PLoS One ; 15(8): e0237086, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32764782

RESUMEN

Paramylon is a novel ß-glucan that is stored by Euglena gracilis Z, which is a unicellular photosynthesizing green alga with characteristics of both animals and plants. Recent studies have indicated that paramylon functions as an immunomodulator or a dietary fiber. Currently, chronic kidney disease (CKD) is a global health problem, and there is no effective preventive treatment for CKD progression. However, paramylon may suppress the progression of CKD via the elimination of uremic toxins or modulation of gut microbiota, leading to the alleviation of inflammation. The aim of this study was to evaluate the effect of paramylon in CKD rat model. Eight-week-old male Wistar rats with a 5/6 nephrectomy were given either a normal diet or a diet containing 5% paramylon for 8 weeks. Proteinuria was measured intermittently. Serum and kidney tissues were harvested after sacrifice. We performed a renal molecular and histopathological investigation, serum metabolome analysis, and gut microbiome analysis. The results showed that paramylon attenuated renal function, glomerulosclerosis, tubulointerstitial injury, and podocyte injury in the CKD rat model. Renal fibrosis, tubulointerstitial inflammatory cell infiltration, and proinflammatory cytokine gene expression levels tended to be suppressed with paramylon treatment. Further, paramylon inhibited the accumulation of uremic toxins, including tricarboxylic acid (TCA) cycle-related metabolites and modulated a part of CKD-related gut microbiota in the CKD rat model. In conclusion, we suggest that paramylon mainly inhibited the absorption of non-microbiota-derived uremic solutes, leading to protect renal injury via anti-inflammatory and anti-fibrotic effects. Paramylon may be a novel compound that can act against CKD progression.


Asunto(s)
Glucanos/farmacología , Riñón/efectos de los fármacos , Sustancias Protectoras/farmacología , Proteinuria/tratamiento farmacológico , Insuficiencia Renal Crónica/tratamiento farmacológico , Administración Oral , Animales , Ciclo del Ácido Cítrico/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Euglena gracilis/química , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/inmunología , Glucanos/aislamiento & purificación , Glucanos/uso terapéutico , Humanos , Mediadores de Inflamación/metabolismo , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiología , Riñón/inmunología , Riñón/patología , Masculino , Sustancias Protectoras/aislamiento & purificación , Sustancias Protectoras/uso terapéutico , Proteinuria/sangre , Proteinuria/patología , Ratas , Ratas Wistar , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/orina , Toxinas Biológicas/sangre , Toxinas Biológicas/metabolismo
16.
Khirurgiia (Mosk) ; (7): 76-81, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-32736467

RESUMEN

OBJECTIVE: To evaluate symptom-modifying effects of a two-month parenteral therapy with chondroitin sulfate («Mucosat¼) in patients with knee and/or hip osteoarthritis (OA) in various combinations of adjuvant therapy. MATERIAL AND METHODS: There were 70 patients with primary and/or post-traumatic unilateral/bilateral knee and/or hip osteoarthritis (Kellgren-Lawrence grade I-II). Pain syndrome severity was assessed as ≥ 50 mm (100-mm VAS), total Leken's index - ≥ 5 points. The main group comprised 40 patients who received Mucosat for 60 days. NSAIDs were additionally prescribed in 9 (22.5%) of these patients. The control group included 30 patients with intra-articular injection of hyaluronic acid. All patients underwent clinical and functional examination (rating scales VAS, Leken's total index, WOMAC index, EQ-5D health questionnaire), laboratory diagnosis (IL-1, IL-6, TNF-α), X-ray examination, assessment of adverse events at 5 visits. RESULTS AND CONCLUSION: Administration of chondroitin sulfate is associated with reduced local pain syndrome and functional normalization of musculoskeletal system. Prolonged pain-free period with high safety profile due to reduced need for NSAIDs is an advantage of Mucosat therapy. Thus, this drug may be recommended for initial therapy. A combination of chondroitin sulfate with intra-articular injection of hyaluronic acid may be perspective for optimization of therapy and secondary prevention of exacerbations of OA. Further research is required.


Asunto(s)
Sulfatos de Condroitina/uso terapéutico , Ácido Hialurónico/uso terapéutico , Osteoartritis de la Cadera/tratamiento farmacológico , Osteoartritis de la Rodilla/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Artralgia/tratamiento farmacológico , Artralgia/etiología , Sulfatos de Condroitina/administración & dosificación , Humanos , Ácido Hialurónico/administración & dosificación , Inyecciones Intraarticulares , Osteoartritis de la Cadera/complicaciones , Osteoartritis de la Rodilla/complicaciones , Sustancias Protectoras/administración & dosificación , Resultado del Tratamiento
17.
Life Sci ; 258: 118153, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32738361

RESUMEN

AIMS: Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly with or without focal and segmental glomerulosclerosis lesions. Isothiocyanate sulforaphane (SFN) can protect kidneys from ORG-related damages. In this study, we investigated the effects of SFN as a preventive therapy or intervention for ORG to reveal its mechanism of action. MAIN METHODS: We established a mouse obesity model with preventive SFN or N-acetylcysteine treatment for 2 months. Thereafter, we used nuclear factor erythroid 2-related factor 2-deficient (Nrf2-/-) and wild type mice in our ORG model with SFN treatment. Finally, we generated a corresponding mouse podocyte model in vitro. The body weight, wet weight of perirenal-and peritesticular fat, and urinary albumin/creatinine ratio were assessed. We used periodic acid-Schiff staining and electron microscopy to assess the function of the kidneys and podocytes. In addition, we evaluated the expression of Nrf2 and podocyte-specific proteins by western blotting. KEY FINDINGS: Treatment with SFN reduced body weight, organ-associated fat weight, and urinary albumin/creatinine ratio in both the preventive treatment and disease intervention regimens. SFN treated mice exhibited higher expression levels of podocyte-specific proteins and better podocyte function. However, treatment with SFN did not affect these parameters in obese Nrf2-/- mice. Light chain 3 of microtubule-associated protein 1-II and metallothionein had higher expression in the wild type than in the Nrf2-/- mice. SIGNIFICANCE: Treatment with SFN limited ORG-induced damage by enhancing podocyte autophagy via Nrf2.


Asunto(s)
Isotiocianatos/uso terapéutico , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/etiología , Factor 2 Relacionado con NF-E2/metabolismo , Obesidad/complicaciones , Sustancias Protectoras/uso terapéutico , Animales , Autofagia/efectos de los fármacos , Células Cultivadas , Enfermedades Renales/metabolismo , Glomérulos Renales/citología , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/metabolismo , Masculino , Ratones Endogámicos C57BL , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Podocitos/citología , Podocitos/efectos de los fármacos , Podocitos/metabolismo
18.
Chem Biol Interact ; 329: 109213, 2020 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-32739323

RESUMEN

Phytoestrogens are plant-derived substances with a similar structure to 17-beta-estradiol, which have protective roles in estrogen-dependent diseases. Isoflavones, the most well-known subgroup of phytoestrogens, play protective roles against chemicals-induced liver injuries through several molecular mechanisms. Hepatoprotective effects of isoflavones are, partly, associated with their antioxidant, anti-inflammatory, immunomodulatory, and anti-fibrotic properties. Besides, isoflavones can reduce gut-derived endotoxins, accelerate alcohol metabolism, stimulate detoxification of hepatotoxic chemicals, suppress the bioactivation of these chemicals, inhibit hepatocytes apoptosis, and restore autophagy activity during chemicals-induced liver diseases. This review provides a summary of the molecular mechanisms underlying the hepatoprotective effects of isoflavones. It seems that further studies are needed to investigate the hepatoprotective potential of isoflavones in patients with different stages of chemicals-induced liver injuries.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Isoflavonas/metabolismo , Sustancias Protectoras/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Modelos Animales de Enfermedad , Inflamación/prevención & control , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Metabolismo de los Lípidos/efectos de los fármacos , Cirrosis Hepática/metabolismo , Cirrosis Hepática/prevención & control , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/metabolismo , Sustancias Protectoras/farmacología
20.
Ulus Travma Acil Cerrahi Derg ; 26(4): 509-516, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32589239

RESUMEN

BACKGROUND: The hypothesis of our study is that sugammadex has protective efficacy against ischemia-reperfusion (I/R) injury in rats. METHODS: Our study included 28 male Wistar Albino rats. The rats were assigned to four groups. The sham group had no procedure other than anesthesia administration. The control group received three hours of ischemia and 24 hours of reperfusion. The Sgdx4 group received 4 mg/kg, and the Sgdx16 group received 16 mg/kg sugammadex intravenously, and then, reperfusion was applied. Histopathological investigation, and serum creatine kinase (CK), lactate dehydrogenase (LDH), and serum and tissue malondialdehyde (MDA) and superoxide dismutase (SOD) analyses were performed. RESULTS: When the sham group and the control group were compared, there were statistically significant differences histopathologically (p<0.01). There was no significant difference between the Sgdx4 group compared with the sham and control groups histopathologically (p>0.01). There was a significant difference between the Sgdx16 group and the sham group histopathologically (p<0.01). There were significant differences between the sham and control groups concerning CK and LDH levels (p<0.01). There was a significant difference in the levels of CK between the control group and Sgdx4 group and in the levels of CK and LDH between the control group and Sgdx16 group (p<0.01). CONCLUSION: In our study, we examined the histological and biochemical protective effects of 4 mg/kg sugammadex on unilateral lower extremity I/R injury in rats. The findings suggest that a 4 mg/kg dose of sugammadex was more effective than a 16 mg/kg dose.


Asunto(s)
Sustancias Protectoras , Daño por Reperfusión , Sugammadex , Animales , Modelos Animales de Enfermedad , Extremidad Inferior/fisiopatología , Masculino , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/uso terapéutico , Ratas , Ratas Wistar , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Sugammadex/administración & dosificación , Sugammadex/uso terapéutico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...