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BACKGROUND: Human Milk (HM) is a dynamic nourishment; its composition is influenced by several conditions such as gestational age, maternal diet and ethnicity. It appears important to evaluate the impact that gestational pathologies have on HM components and if their presence, as a source of oxidative stress in the mother, influence milk's redox homeostasis. To assess the effect of Preeclampsia (PE) and Gestational Diabetes Mellitus (GDM) on some aspects of human milk redox homeostasis, we chose to investigate both oxidative and antioxidant aspects, with, respectively, Lipid hydroperoxides (LOOHs) and Glutathione (GSH). METHODS: Women with PE, GDM and who were healthy were recruited for this study. Colostrum, transitional and mature milk samples were collected. GSH and LOOHs levels were measured using a spectrophotometric test. To investigate the effect of pathology on redox homeostasis, a mixed linear model with unistructural covariance structure was performed. RESULTS: A total of 120 mothers were recruited. The GSH concentration results were significantly lower in GDM women than in healthy women only in colostrum (p < 0.01). No other differences emerged. LOOHs was not detectable in almost all the samples. DISCUSSION: Our study is the first to extensively evaluate these components in the HM of women with these gestational pathologies. The main observation is that GDM can alter the GSH level of HM, mainly in colostrum.
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Diabetes Gestacional , Leche Humana , Embarazo , Femenino , Humanos , Leche Humana/química , Calostro/química , Madres , Oxidación-ReducciónRESUMEN
A nanometric hybrid system consisting of a Fe3O4 magnetic nanoparticles modified through the growth of Fe-based Metal-organic frameworks of the MIL (Materials Institute Lavoiser) was developed. The obtained system retains both the nanometer dimensions and the magnetic properties of the Fe3O4 nanoparticles and possesses increased the loading capability due to the highly porous Fe-MIL. It was tested to load, carry and release temozolomide (TMZ) for the treatment of glioblastoma multiforme one of the most aggressive and deadly human cancers. The chemical characterization of the hybrid system was performed through various complementary techniques: X-ray-diffraction, thermogravimetric analysis, FT-IR and X-ray photoelectron spectroscopies. The nanomaterial showed low toxicity and an increased adsorption capacity compared to bare Fe3O4 magnetic nanoparticles (MNPs). It can load about 12 mg/g of TMZ and carry the drug into A172 cells without degradation. Our experimental data confirm that, after 48 h of treatment, the TMZ-loaded hybrid nanoparticles (15 and 20 µg/mL) suppressed human glioblastoma cell viability much more effectively than the free drug. Finally, we found that the internalization of the MIL-modified system is more evident than bare MNPs at all the used concentrations both in the cytoplasm and in the nucleus suggesting that it can be capable of overcoming the blood-brain barrier and targeting brain tumors. In conclusion, these results indicate that this combined nanoparticle represents a highly promising drug delivery system for TMZ targeting into cancer cells.
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Glioblastoma , Nanopartículas de Magnetita , Nanopartículas , Humanos , Línea Celular Tumoral , Glioblastoma/metabolismo , Nanopartículas de Magnetita/química , Nanopartículas/química , Espectroscopía Infrarroja por Transformada de Fourier , Temozolomida/farmacología , Temozolomida/uso terapéuticoRESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) represents a serious threat to public health, due to its large variety of pathogenetic mechanisms. Accordingly, the present study aimed to investigate the anti-MRSA activities of Krameria lappacea, a medicinal plant native to South America. Through Ultra-High-Performance Liquid Chromatography coupled with High-Resolution Mass spectrometry, we analyzed the chemical composition of Krameria lappacea root extract (KLRE). The antibacterial activity of KLRE was determined by the broth microdilution method, also including the minimum biofilm inhibitory concentration and minimum biofilm eradication concentration. Besides, we evaluated the effect on adhesion and invasion of human lung carcinoma A549 cell line by MRSA strains. The obtained results revealed an interesting antimicrobial action of this extract, which efficiently inhibit the growth, biofilm formation, adhesion and invasion of MRSA strains. Furthermore, the chemical analysis revealed the presence in the extract of several flavonoid compounds and type-A and type-B proanthocyanidins, which are known for their anti-adhesive effects. Taken together, our findings showed an interesting antimicrobial activity of KLRE, giving an important contribution to the current knowledge on the biological activities of this plant.
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Natural bioactive compounds may be used in obese patients because of their ability to impact on various key mechanisms involved in the complex pathophysiological mechanisms of such condition. The aim of this study was to investigate the effect of a Mangifera indica L. leaf extract (MLE) on adipogenic differentiation of murine preadipocyte cells. 3T3-L1 cells were treated during their differentiation with various concentrations of (Mangifera indica L.) leaves extract (MLE) (750, 380, 150, 75 and 35 µg) in order to assess their lipid content, adiponectin production, expression profile of genes involved in lipid metabolism, oxidative stress and inflammation. Our results showed that MLE was particularly enriched in polyphenols (46.30 ± 0.083 mg/g) and that pharmacological treatment of cells resulted in a significant increase of adiponectin levels and reduction of intracellular lipid content. Consistently with these results, MLE resulted in a significant decrease of the expression of genes involved in lipid metabolism (FAS, PPARG, DGAT1, DGAT2, and SCD-1). In conclusion, our results suggest that MLE may represent a possible pharmacological tool for obese or metabolic syndrome patients.
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Adipocitos/efectos de los fármacos , Adipogénesis , Adiponectina/metabolismo , Antioxidantes/farmacología , Mangifera/química , Extractos Vegetales/farmacología , Células 3T3-L1 , Adipocitos/metabolismo , Animales , Antioxidantes/química , Metabolismo de los Lípidos , Ratones , Estrés Oxidativo , Extractos Vegetales/química , Hojas de la Planta/química , Polifenoles/análisis , Xantonas/análisisRESUMEN
Iron toxicity is associated with organ injury and has been reported in various clinical conditions, such as hemochromatosis, thalassemia major, and myelodysplastic syndromes. Therefore, iron chelation therapy represents a pivotal therapy for these patients during their lifetime. The aim of the present study was to assess the iron chelating properties of α-lipoic acid (ALA) and how such an effect impacts on iron overload mediated toxicity. Human mesenchymal stem cells (HS-5) and animals (zebrafish, n = 10 for each group) were treated for 24 h with ferric ammonium citrate (FAC, 120 µg/mL) in the presence or absence of ALA (20 µg/mL). Oxidative stress was evaluated by reduced glutathione content, reactive oxygen species formation, mitochondrial dysfunction, and gene expression of heme oxygenase-1b and mitochondrial superoxide dismutase; organ injury, iron accumulation, and autophagy were measured by microscopical, cytofluorimetric analyses, and inductively coupled plasmaâoptical mission Spectrometer (ICP-OES). Our results showed that FAC results in a significant increase of tissue iron accumulation, oxidative stress, and autophagy and such detrimental effects were reversed by ALA treatment. In conclusion, ALA possesses excellent iron chelating properties that may be exploited in a clinical setting for organ preservation, as well as exhibiting a good safety profile and low cost for the national health system.
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Compuestos Férricos/efectos adversos , Quelantes del Hierro/administración & dosificación , Sobrecarga de Hierro/tratamiento farmacológico , Compuestos de Amonio Cuaternario/efectos adversos , Ácido Tióctico/administración & dosificación , Animales , Autofagia/efectos de los fármacos , Línea Celular , Modelos Animales de Enfermedad , Glutatión/metabolismo , Hemo-Oxigenasa 1/genética , Humanos , Quelantes del Hierro/farmacología , Sobrecarga de Hierro/inducido químicamente , Sobrecarga de Hierro/genética , Sobrecarga de Hierro/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/genética , Ácido Tióctico/farmacología , Pez CebraRESUMEN
BACKGROUND: The molecular nature of lipoic acid (LA) clarifies its capability of taking part to a variety of biochemical reactions where redox state is meaningful. The pivotal action of LA is the antioxidant activity due to its ability to scavenge and inactivate free radicals. Furthermore, LA has been shown to chelate toxic metals both directly and indirectly by its capability to enhance intracellular glutathione (GSH) levels. This last property is due to its ability to interact with GSH and recycle endogenous GSH. LA exhibits significant antioxidant activity protecting against oxidative damage in several diseases, including neurodegenerative disorders. Interestingly, LA is unique among natural antioxidants for its capability to satisfy a lot of requirements, making it a potentially highly effective therapeutic agent for many conditions related with oxidative damage. In particular, there are evidences showing that LA has therapeutic activity in lowering glucose levels in diabetic conditions. Similarly, LA supplementation has multiple beneficial effects on the regression of the mitochondrial function and on oxidative stress associated with several diseases and aging. AIM: The aim of the present review is to describe the molecular mechanisms underlying the beneficial effects of LA under various experimental conditions and disease and how to exploit such effect for clinical purposes. CONCLUSION: LA has pleiotropic effects in different pathways related with several diseases, its use as a potential therapeutic agent is very promising.
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Antiinflamatorios , Antioxidantes , Ácido Tióctico , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Humanos , Transducción de Señal , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéuticoRESUMEN
Coffee is the most consumed beverage worldwide. Epidemiological studies with prospective cohorts showed that coffee intake is associated with reduced cardiovascular and all-cause mortality independently of caffeine content. Cohort and case-control studies reported an inverse association between coffee consumption and the degree of liver fibrosis as well as the development of liver cancer. Furthermore, the beneficial effects of coffee have been recently confirmed by large meta-analyses. In the last two decades, various in vitro and in vivo studies evaluated the molecular determinants for the hepatoprotective effects of coffee. In the present article, we aimed to critically review experimental evidence regarding the active components and the molecular bases underlying the beneficial role of coffee against chronic liver diseases. Almost all studies highlighted the beneficial effects of this beverage against liver fibrosis with the most solid results indicating a pivot role for both caffeine and chlorogenic acids. In particular, in experimental models of fibrosis, caffeine was shown to inhibit hepatic stellate cell activation by blocking adenosine receptors, and emerging evidence indicated that caffeine may also favorably impact angiogenesis and hepatic hemodynamics. On the other side, chlorogenic acids, potent phenolic antioxidants, suppress liver fibrogenesis and carcinogenesis by reducing oxidative stress and counteract steatogenesis through the modulation of glucose and lipid homeostasis in the liver. Overall, these molecular insights may have translational significance and suggest that coffee components need clinical evaluation.
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Café/química , Cirrosis Hepática/prevención & control , Hígado/efectos de los fármacos , Animales , Cafeína/farmacología , Ácido Clorogénico/farmacología , Modelos Animales de Enfermedad , Hígado Graso/tratamiento farmacológico , Hígado Graso/prevención & control , Humanos , Metabolismo de los Lípidos , Hígado/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/prevención & control , Extractos Vegetales/farmacología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Statins are the most common used lipid lowering drugs but they may cause adverse effects and despite their well-established therapeutic benefits residual cardiovascular (CV) risk remains. The use of other lipid lowering drugs and nutraceuticals alone or as add-on lipid-modifying therapy can be an option in such cases. Several studies have reported health-related properties of the Citrus fruits, among which bergamot (Citrus bergamia Risso) differs from others by particularly high content of certain compounds. PURPOSE: This narrative review summarizes the current evidence on the effects of bergamot on lipid parameters based on studies involving animals and humans. MAIN EVIDENCE: This natural supplement may lead to effective lipid-lowering treatment. Its lipid-lowering activity is attributed to different flavonoids. However, the exact mechanisms involved remain unclear. CONCLUSION: It is expected that ongoing and future studies will confirm the benefit of bergamot in dyslipidemic and other cardiometabolic disorders, potentially leading to reduced overall CV risk.
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Dislipidemias/tratamiento farmacológico , Flavonoides/farmacología , Hipolipemiantes/farmacología , Hipolipemiantes/uso terapéutico , Extractos Vegetales/farmacología , Animales , Citrus/química , Flavonoides/uso terapéutico , Humanos , Extractos Vegetales/uso terapéuticoRESUMEN
Coffee consists of several biological active compounds, such as caffeine, diterpenes, chlorogenic acids, and melanoidins, which may affect human health. The intake of each compound depends on the variety of coffee species, roasting degree, type of brewing method and serving size. The bioavailability and the distribution of each compound and its metabolites also contribute to coffee mechanisms of action. The health benefits of coffee consumption regarding cardiovascular system and metabolism mostly depend on its antioxidant compounds. In contrast, diterpenes and caffeine may produce harmful effects by raising lipid fraction and affecting endothelial function, respectively. Studying the mechanism of action of coffee components may help understanding whether coffee's impact on health is beneficial or hazardous. In this article, we reviewed the available information about coffee compounds and their mechanism of action. Furthermore, benefits and risks for cardiovascular system associated with coffee consumption will be discussed.
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Alcaloides/farmacología , Cafeína/farmacología , Sistema Cardiovascular/efectos de los fármacos , Ácido Clorogénico/farmacología , Café/química , Diterpenos/farmacología , Polímeros/farmacología , Alcaloides/efectos adversos , Alcaloides/uso terapéutico , Cafeína/efectos adversos , Cafeína/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Ácido Clorogénico/efectos adversos , Ácido Clorogénico/uso terapéutico , Café/efectos adversos , Diabetes Mellitus Tipo 2/prevención & control , Diterpenos/efectos adversos , Diterpenos/uso terapéutico , Humanos , Extractos Vegetales/efectos adversos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Polímeros/efectos adversos , Polímeros/uso terapéutico , Polifenoles/efectos adversos , Polifenoles/farmacología , Polifenoles/uso terapéuticoRESUMEN
OBJECTIVE: To investigate the role of heme oxygenase (HO) system in moderate to severe benign prostatic hyperplasia and lower urinary tract symptom patients and the influence of metabolic syndrome (MetS) components on HO-1 or HO-2 prostatic levels. METHODS: One hundred thirty-two consecutive patients who underwent transurethral resection of the prostate were prospectively enrolled. MetS was defined by the International Diabetes Federation. Patients were divided in 2 groups: group A (high-density lipoprotein-cholesterol [HDL-C]≥40 mg/dL and triglycerides<150 mg/dL) and group B (HDL-C<40 mg/dL and triglycerides≥150 mg/dL). Surgical specimens were collected for HO level determination. HO-1 levels were determined by enzyme-linked immunosorbent assay and HO-1 levels by Western blotting. RESULTS: Patients with MetS showed lower levels of HO-1 (5.29 vs 6.28 ng/mL; P=.04), HO-2 (1.01 vs 1.83 ng/mL; P=.04), phosphorylated activated protein kinase (pAMPK; 0.62 vs 1.11 AUI; P<.01), and HO-activity (61.43 vs 70.22 AUI; P<.01) with respect to normal. The Pearson correlation analysis showed that HO-1, HO-2, and HO activity were negatively associated with waist circumference (P<.05), body mass index (P<.05), triglycerides (P<.05) and positively with HDL-C (P<.05). Group B showed lower levels of HO-1 (4.7 vs 6.6 ng/mL; P<.05), HO-2 (1.4 vs 0.4 ng/mL; P=.03), HO-activity (69.63 vs 58.42 AUI; P=.04), and higher International Prostate Symptoms Score (21.4 vs 25.0; P<.05) with respect to group A. The enzyme-linked immunosorbent assay showed that HO-1 and HO activity levels were significantly lower in group B compared with group A. Reduced HDL-C and elevated triglyceride levels decreased HO-1 expression in the prostate tissue. Western blot analysis of tissue samples showed significant differences in basal protein expression levels of HO-2 and pAMPK in group B compared with group A. CONCLUSION: Alteration of serum triglycerides and HDL-C significantly impairs HO-1 and HO-2 levels in benign prostatic hyperplasia patients.
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Hemo Oxigenasa (Desciclizante)/sangre , Síntomas del Sistema Urinario Inferior/sangre , Hiperplasia Prostática/sangre , Hiperplasia Prostática/patología , Triglicéridos/sangre , Anciano , Anciano de 80 o más Años , Western Blotting , HDL-Colesterol/sangre , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática , Humanos , Síntomas del Sistema Urinario Inferior/complicaciones , Síntomas del Sistema Urinario Inferior/patología , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/cirugía , Sensibilidad y Especificidad , Resección Transuretral de la Próstata/métodosRESUMEN
Coffee consumption is inversely related to the degree of liver injury in patients with nonalcoholic fatty liver disease (NAFLD). Molecular mediators contributing to coffee's beneficial effects in NAFLD remain to be elucidated. In this study, we administrated decaffeinated espresso coffee or vehicle to rats fed an high-fat diet (HFD) for 12 weeks and examined the effects of coffee on liver injury by using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) proteomic analysis combined with mass spectrometry. Rats fed an HFD and water developed panacinar steatosis, lobular inflammation, and mild fibrosis, whereas rats fed an HFD and coffee exhibited only mild steatosis. Coffee consumption increased liver expression of the endoplasmic reticulum chaperones glucose-related protein 78 and protein disulfide-isomerase A3; similarly, coffee drinking enhanced the expression of the mitochondrial chaperones heat stress protein 70 and DJ-1. Furthermore, in agreement with reduced hepatic levels of 8-isoprostanes and 8-hydroxy-2'-deoxyguanosine, proteomic analysis showed that coffee consumption induces the expression of master regulators of redox status (i.e., peroxiredoxin 1, glutathione S-transferase α2, and D-dopachrome tautomerase). Last, proteomics revealed an association of coffee intake with decreased expression of electron transfer flavoprotein subunit α, a component of the mitochondrial respiratory chain, involved in de novo lipogenesis. In this study, we were able to identify by proteomic analysis the stress proteins mediating the antioxidant effects of coffee; moreover, we establish for the first time the contribution of specific coffee-induced endoplasmic reticulum and mitochondrial chaperones ensuring correct protein folding and degradation in the liver.
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Café , Hígado Graso/dietoterapia , Hígado Graso/metabolismo , Chaperonas Moleculares/metabolismo , Animales , Antioxidantes/metabolismo , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Electroforesis en Gel Bidimensional , Retículo Endoplásmico/metabolismo , Hígado Graso/genética , Expresión Génica , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas de Choque Térmico/biosíntesis , Proteínas de Choque Térmico/genética , Masculino , Mitocondrias Hepáticas/metabolismo , Enfermedad del Hígado Graso no Alcohólico , Proteína Disulfuro Isomerasas/genética , Proteína Disulfuro Isomerasas/metabolismo , Proteómica , Ratas , Ratas Wistar , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Espectrometría de Masas en Tándem , Investigación Biomédica TraslacionalRESUMEN
Maternal antenatal therapy with glucocorticoids (GC) is routinely used to prevent lung immaturity. The potential harmful effects on other organs, including in particular the central nervous system (CNS), are still controversial. In the present review we aimed to investigate: i) the beneficial and detrimental effects of antenatal GC treatment in both human and animal models; ii) the potential usefulness of biochemical markers such as calcium binding proteins (S100B, synaptophysin) and cytoskeletal protein of neurons and dendrites (MAP2) in the perinatal period, and iii) whether the assessment of brain markers in different biological fluids could constitute a promising tool for the monitoring of CNS function and/or developmental in fetuses and newborns whose mothers assumed GC antenatally.
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Sistema Nervioso Central/efectos de los fármacos , Glucocorticoides/uso terapéutico , Intercambio Materno-Fetal , Animales , Sistema Nervioso Central/embriología , Femenino , Glucocorticoides/farmacología , Humanos , Recién Nacido , Embarazo , Receptores de Glucocorticoides/metabolismo , Síndrome de Dificultad Respiratoria del Recién Nacido/prevención & controlRESUMEN
Identification of imatinib mesylate as a potent inhibitor of the Abl kinase and the subsequent findings that this compound displays growth inhibitory and pro-apoptotic effects in Bcr-Abl+ cells, has deeply conditioned CML treatment. Unfortunately the initial striking efficacy of this drug has been overshadowed by the development of clinical resistance. A wide variety of molecular mechanisms can underlie such resistance mechanisms. In the recent years, heme oxygenase-1 (HO-1) expression has been reported as an important protective endogenous mechanism against physical, chemical and biological stress and this cytoprotective role has already been demonstrated for several solid tumors and acute leukemias. The aim of the present study was to investigate the effect of HO-1 expression on cell proliferation and apoptosis in chronic myeloid leukemia cells, K562 and LAMA-84 cell lines following imatinib treatment. Cells were incubated for 24h with Imatinib (1 µM) alone or in combination with Hemin (10µM), an inducer of HO-1. In addition, cells were also treated with HO byproducts, bilirubin and carbon monoxide (CO), or with a protease inhibitor (Ed64) to inhibit HO-1 nuclear translocation. Pharmacological induction of HO-1 was able to overcome the effect of imatinib. The cytoprotective effect of HO-1 was further confirmed after silencing HO-1 by siRNA. Interestingly, neither bilirubin nor CO was able to protect cells from Imatinib-induced toxicity. By contrast, the protective effect of HO-1 was mitigated by the addition of E64d, preventing HO-1 nuclear translocation. Finally, imatinib was able to increase the formation of cellular reactive oxygen species (ROS) and this effect was reversed by HO-1 induction or the addition of N-acetylcisteine (NAC). In conclusion, the protective effect of HO-1 on imatinib-induced cytotoxicity does not involve its enzymatic byproducts, but rather the nuclear translocation of HO-1 following proteolytic cleavage.
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Antineoplásicos/uso terapéutico , Benzamidas/uso terapéutico , Núcleo Celular/metabolismo , Hemo-Oxigenasa 1/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Resistencia a Antineoplásicos , Silenciador del Gen , Hemo-Oxigenasa 1/genética , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
This study investigated the effect of cyanidin-3-O-ß-glucoside on an experimental model of partial/transient cerebral ischemia in the rats in order to verify the effectiveness of both pre- and posttreatments. Cyanidin-3-O-ß-glucoside-pretreated rats were injected with 10 mg/Kg i.p. 1 h before the induction of cerebral ischemia; in posttreated rats, the same dosage was injected during reperfusion (30 min after restoring blood flow). Cerebral ischemia was induced by bilateral clamping of common carotid arteries for 20 min. Ischemic rats were sacrificed immediately after 20 min ischemia; postischemic reperfused animals were sacrificed after 3 or 24 h of restoring blood flow. Results showed that treatment with cyanidin increased the levels of nonproteic thiol groups after 24 h of postischemic reperfusion, significantly reduced the lipid hydroperoxides, and increased the expression of heme oxygenase and γ-glutamyl cysteine synthase; a significant reduction in the expression of neuronal and inducible nitric oxide synthases and the equally significant increase in the endothelial isoform were observed. Significant modifications were also detected in enzymes involved in metabolism of endogenous inhibitors of nitric oxide. Most of the effects were observed with both pre- and posttreatments with cyanidin-3-O-ß-glucoside suggesting a role of anthocyanin in both prevention and treatment of postischemic reperfusion brain damage.
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OBJECTIVE: There is growing evidence on the usefulness of biomarkers in the early detection of preterm infants at risk for brain damage. However, among different tools Activin A, S100B protein and adrenomedullin assessment offer the possibility to investigate brain/multiorgan function and development. This could be especially useful in perinatal medicine that requires even more non-invasive techniques in order to fulfill the minimal handling in diagnostic and therapeutic strategy performance. MATERIALS AND METHODS: The concept of Unconventional Biological Fluid (UBF: urine and saliva) is becoming even stronger and regards the assessment in non-invasive biological fluids of biochemical markers involved in the cascade of events leading to brain damage. RESULTS: Activin A, S100B protein and adrenomedullin in UBF were increased in preterm newborns developing brain damage and/or ominous outcome. CONCLUSIONS: The present manuscript offers an update on the usefulness of Activin A, S100B protein an adrenomedullin in UBF as brain damage markers. The findings open a new cue on the use of these markers in daily neonatal intensive care unit (NICU) activities.
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Biomarcadores/análisis , Lesiones Encefálicas/diagnóstico , Enfermedades del Prematuro/diagnóstico , Recien Nacido Prematuro , Activinas/análisis , Activinas/genética , Activinas/metabolismo , Adrenomedulina/análisis , Adrenomedulina/genética , Adrenomedulina/metabolismo , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/metabolismo , Biomarcadores/orina , Lesiones Encefálicas/líquido cefalorraquídeo , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/orina , Humanos , Recién Nacido , Recien Nacido Prematuro/líquido cefalorraquídeo , Recien Nacido Prematuro/metabolismo , Recien Nacido Prematuro/orina , Enfermedades del Prematuro/líquido cefalorraquídeo , Enfermedades del Prematuro/metabolismo , Enfermedades del Prematuro/orina , Factores de Crecimiento Nervioso/análisis , Factores de Crecimiento Nervioso/genética , Factores de Crecimiento Nervioso/metabolismo , Subunidad beta de la Proteína de Unión al Calcio S100 , Proteínas S100/análisis , Proteínas S100/genética , Proteínas S100/metabolismo , Saliva/química , Saliva/metabolismoRESUMEN
BACKGROUND: Nonalcoholic fatty liver disease is a chronic metabolic disorder with significant impact on cardiovascular and liver mortality. AIMS: In this study, we examined the effects of silibinin on liver and myocardium injury in an experimental model of nonalcoholic fatty liver disease. METHODS: A four-week daily dose of silibinin (20 mg/kg i.p.) was administrated to db/db mice fed a methionine-choline deficient diet. Hepatic and myocardial histology, oxidative stress and inflammatory cytokines were evaluated. RESULTS: Silibinin administration decreased HOMA-IR, serum ALT and markedly improved hepatic and myocardial damage. Silibinin reduced isoprostanes, 8-deoxyguanosine and nitrites/nitrates in the liver and in the heart of db/db fed the methionine-choline deficient diet, whereas glutathione levels were restored to lean mice levels in both tissues. Consistently, liver mitochondrial respiratory chain activity was significantly impaired in untreated mice and was completely restored in silibinin-treated animals. TNF-α was increased whereas IL-6 was decreased both in the liver and heart of db/db fed methionine-choline deficient diet. Silibinin reversed heart TNF-α and IL-6 expression to control mice levels. Indeed, liver JNK phosphorylation was reduced to control levels in treated animals. CONCLUSIONS: This study demonstrates a combined effectiveness of silibinin on improving liver and myocardial injury in experimental nonalcoholic fatty liver disease.
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Antioxidantes/uso terapéutico , Hígado Graso/tratamiento farmacológico , Hígado Graso/patología , Miocardio/patología , Silimarina/uso terapéutico , Alanina Transaminasa/sangre , Alanina Transaminasa/efectos de los fármacos , Análisis de Varianza , Animales , Antioxidantes/farmacología , Deficiencia de Colina/metabolismo , Citocinas/efectos de los fármacos , Citocinas/genética , Citocinas/metabolismo , Dieta , Hígado Graso/sangre , Expresión Génica/efectos de los fármacos , Glutatión/efectos de los fármacos , Glutatión/metabolismo , Resistencia a la Insulina , Isoprostanos/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Hígado/metabolismo , Hígado/patología , Masculino , Metionina/deficiencia , Ratones , Miocardio/metabolismo , Nitratos/metabolismo , Nitritos/metabolismo , Enfermedad del Hígado Graso no Alcohólico , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos , Silibina , Silimarina/farmacología , Estadísticas no ParamétricasRESUMEN
Cancer of the esophagus is the eighth most common cancer by incidence worldwide and ranks sixth as the most common cause of cancer death. It is unique among the gastrointestinal tract malignancies because it embodies two distinct histopatologic types, squamous cell carcinoma and adenocarcinoma. Which type of cancer occurs in a given patient or predominates in a given geographic area depends on many variables, including individual lifestyle, socioeconomic pressures, environmental factors and diet and nutrition. Generally for both squamous cell carcinoma and adenocarcinoma of the esophagus case-control studies provide evidence of a protective effect of fruits and vegetables. Here we review the role of nutrition in the etiology of esophageal cancer.
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Dieta , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/prevención & control , Consumo de Bebidas Alcohólicas , Grasas de la Dieta/administración & dosificación , Frutas , Humanos , Carne , Nitrosaminas/administración & dosificación , Factores de Riesgo , Té , VerdurasRESUMEN
AIM: To evaluate the efficacy of L-carnitine on alleviating anemia, thrombocytopenia and leukopenia, and minimizing dose reductions in patients with chronic hepatitis C virus (HCV) in treatment with Interferon α (IFN-α) plus ribavirin. METHODS: Sixty-nine patients with chronic hepatitis C were enrolled in the study and divided into two groups. group A (n = 35) received Peg-IFN-α 2b plus ribavirin plus L-carnitine, and group B (n = 34) received Peg-IFN-α and ribavirin for 12 mo. All patients underwent laboratory investigations including: red cell count, hemoglobin, white cell count, platelets, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and viremia. RESULTS: After 12 mo in group A compared to group B we observed significant differences in AST 108.8 vs 76.8 (IU/L; P < 0.001), ALT 137.9 vs 112.3 (IU/L; P < 0.001), viremia 4.04 vs 2.36 (× 10(6) copies/mL; P < 0.001), Hb 1 vs 3.5 (g/dL; P < 0.05), red blood cells 0.3 vs 1.1 (× 10(12)/L; P < 0.001), white blood cells 1.5 vs 3 (× 10(9)/L; P < 0.001) and platelets 86 vs 85 (× 10(9)/L; P < 0.001). The end treatment responders were 18 vs 12 (60% vs 44%) and the non responders were 12 vs 15 (40% vs 50%) [odds ratio (OR) 1.65, 95% CI = 0.65-5.37, P < 0.05]. In group A compared to group B there was a significant improvement of sustained virological response in 15 vs 7 patients (50% vs 25%), while the relapsers were 3 vs 5 (10% vs 18%) (OR 3.57, 95% CI = 0.65-19.3, P < 0.001). CONCLUSION: L-carnitine supplementations modulate erythropoiesis, leucopoiesis and thrombocytopoiesis, and may be useful in patients treated for HCV. L-carnitine treatment offers the possibility of achieving a sustained virological response while preventing overtreatment.
Asunto(s)
Antivirales/uso terapéutico , Carnitina/uso terapéutico , Suplementos Dietéticos , Hepatitis C Crónica/dietoterapia , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Adulto , Carnitina/administración & dosificación , Quimioterapia Combinada , Femenino , Hepacivirus/genética , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
Diabetes mellitus is associated with a higher oxidative stress and reduced activity of the antioxidant defense system in different brain regions. Results from numerous studies reported impaired cognitive and neurochemical function in diabetic patients and streptozotocin induced diabetic rodents. It is well established that polyphenols exert potent antioxidant and protective functions. Based on recent findings, one potential target for the antioxidant/antinflammatory properties of polyphenols is the heme oxygenase (HO)-1 pathway. Among various compounds tested silibinin, the main component of silymarin, has been shown to possess a strong antioxidant effect in various experimental models; however a study on the possible neuroprotective effect of this compound on the brain of diabetic animals is currently lacking. Therefore, we studied and measured in lean mice (db/m) and knock out mice for the leptin receptors mice (db/db) the effect of silibinin on HO-1 protein levels, non proteic thiol groups, isoprostanes and 8-OH deoxyguanosine (markers of lipid peroxidation and DNA damage, respectively) in different brain regions. Our results showed that HO-1 is differently expressed in various brain regions in db/db mice when compared to lean animals. Furthermore, silibinin provides DNA protection and reduces oxidative stress in a brain specific area, in part via the activation of the HO system. Silibinin may provide a valid tool to counteract oxidative stress in the diabetic status in the central nervous system under diabetic condition.
Asunto(s)
Antioxidantes/uso terapéutico , Química Encefálica/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Silimarina/uso terapéutico , Animales , Peso Corporal , Encéfalo/enzimología , Daño del ADN/efectos de los fármacos , Diabetes Mellitus Tipo 2/enzimología , Diabetes Mellitus Tipo 2/genética , Evaluación Preclínica de Medicamentos , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/metabolismo , Metaloporfirinas/farmacología , Ratones , Ratones Noqueados , Ratones Mutantes , Proteínas del Tejido Nervioso/metabolismo , Estrés Oxidativo/efectos de los fármacos , Receptores de Leptina/deficiencia , SilibinaRESUMEN
OBJECTIVES: Nonalcoholic steatohepatitis (NASH) is a known metabolic disorder of the liver. No treatment has been conclusively shown to improve NASH or prevent disease progression. The function of L-carnitine to modulate lipid profile, glucose metabolism, oxidative stress, and inflammatory responses has been shown. The aim of this study was to evaluate the effects of L-carnitine's supplementation on regression of NASH. METHODS: In patients with NASH and control subjects, we randomly dispensed one 1-g L-carnitine tablet after breakfast plus diet and one 1 g tablet after dinner plus diet for 24 weeks or diet alone at the same dosage and regimen. We evaluated liver enzymes, lipid profile, fasting plasma glucose, C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, homeostasis model assessment (HOMA)-IR, body mass index, and histological scores. RESULTS: At the end of the study, L-carnitine-treated patients showed significant improvements in the following parameters: aspartate aminotransferase (P=0.000), alanine aminotransferase (ALT) (P=0.000), gamma-glutamyl-transpeptidase (gamma-GT) (P=0.000), total cholesterol (P=0.000), low-density lipoprotein (LDL) (P=0.000), high-density lipoprotein (HDL) (P=0.000), triglycerides (P=0.000), glucose (P=0.000), HOMA-IR (P=0.000), CRP (P=0.000), TNF-alpha (P=0.000), and histological scores (P=0.000). CONCLUSIONS: L-carnitine supplementation to diet is useful for reducing TNF-alpha and CRP, and for improving liver function, glucose plasma level, lipid profile, HOMA-IR, and histological manifestations of NASH.