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Evidence exists that heart failure (HF) has an overall impact of 1-2 % in the global population being often associated with comorbidities that contribute to increased disease prevalence, hospitalization, and mortality. Recent advances in pharmacological approaches have significantly improved clinical outcomes for patients with vascular injury and HF. Nevertheless, there remains an unmet need to clarify the crucial role of nitric oxide/cyclic guanosine 3',5'-monophosphate (NO/cGMP) signalling in cardiac contraction and relaxation, to better identify the key mechanisms involved in the pathophysiology of myocardial dysfunction both with reduced (HFrEF) as well as preserved ejection fraction (HFpEF). Indeed, NO signalling plays a crucial role in cardiovascular homeostasis and its dysregulation induces a significant increase in oxidative and nitrosative stress, producing anatomical and physiological cardiac alterations that can lead to heart failure. The present review aims to examine the molecular mechanisms involved in the bioavailability of NO and its modulation of downstream pathways. In particular, we focus on the main therapeutic targets and emphasize the recent evidence of preclinical and clinical studies, describing the different emerging therapeutic strategies developed to counteract NO impaired signalling and cardiovascular disease (CVD) development.
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Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/tratamento farmacológico , Óxido Nítrico/metabolismo , Volume Sistólico , Coração , GMP Cíclico/metabolismoRESUMO
The clinical use of anthracycline Doxorubicin as an antineoplastic drug in cancer therapy is limited by cardiotoxic effects that can lead to congestive heart failure. Recent studies have shown several promising activities of different species of the genus Ferula belonging to the Apiaceae Family. Ferula communis is the main source of Ferutinin-a bioactive compound isolated from many species of Ferula-studied both in vitro and in vivo because of their different effects, such as estrogenic, antioxidant, anti-inflammatory, and also antiproliferative and cytotoxic activity, performed in a dose-dependent and cell-dependent way. However, the potential protective role of Ferutinin in myocardium impairment, caused by chemotherapeutic drugs, still represents an unexplored field. The aim of this study was to test the effects of Ferutinin rich-Ferula communis L. root extract (FcFE) at different concentrations on H9C2 cells. Moreover, we evaluated its antioxidant properties in cardiomyocytes in order to explore new potential therapeutic activities never examined before in other experimental works. FcFE, at a concentration of 0.25 µM, in the H9C2 line, significantly reduced the ROS production induced by H2O2 (50 µM and 250 µM) and traced the cell mortality of the H9C2 co-treated with Ferutinin 0.25 µM and Doxorubicin (0.5 µM and 1 µM) to control levels. These results showed that FcFE could protect against Doxorubicin-induced cardiotoxicity. Further molecular characterization of this natural compound may open the way for testing FcFE at low concentrations in vivo and in clinical studies as an adjuvant in cancer therapy in association with anthracyclines to prevent side effects on heart cells.
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Ferula , Neoplasias , Antioxidantes/farmacologia , Peróxido de Hidrogênio , Doxorrubicina/efeitos adversos , Pontos de Checagem do Ciclo Celular , Antraciclinas , Cardiotoxicidade/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Extratos Vegetais/farmacologiaRESUMO
Skeletal muscle atrophy is a condition characterized by a loss of muscle mass and muscle strength caused by an imbalance between protein synthesis and protein degradation. Muscle atrophy is often associated with a loss of bone mass manifesting as osteoporosis. The aim of this study was to evaluate if chronic constriction injury (CCI) of the sciatic nerve in rats can be a valid model to study muscle atrophy and consequent osteoporosis. Body weight and body composition were assessed weekly. Magnetic resonance imaging (MRI) was performed on day zero before ligation and day 28 before sacrifice. Catabolic markers were assessed via Western blot and Quantitative Real-time PCR. After the sacrifice, a morphological analysis of the gastrocnemius muscle and Micro-Computed Tomography (Micro-CT) on the tibia bone were performed. Rats that underwent CCI had a lower body weight increase on day 28 compared to the naive group of rats (p < 0.001). Increases in lean body mass and fat mass were also significantly lower in the CCI group (p < 0.001). The weight of skeletal muscles was found to be significantly lower in the ipsilateral hindlimb compared to that of contralateral muscles; furthermore, the cross-sectional area of muscle fibers decreased significantly in the ipsilateral gastrocnemius. The CCI of the sciatic nerve induced a statistically significant increase in autophagic and UPS (Ubiquitin Proteasome System) markers and a statistically significant increase in Pax-7 (Paired Box-7) expression. Micro-CT showed a statistically significant decrease in the bone parameters of the ipsilateral tibial bone. Chronic nerve constriction appeared to be a valid model for inducing the condition of muscle atrophy, also causing changes in bone microstructure and leading to osteoporosis. Therefore, sciatic nerve constriction could be a valid approach to study muscle-bone crosstalk and to identify new strategies to prevent osteosarcopenia.
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Doenças Ósseas Metabólicas , Atrofia Muscular , Osteoporose , Nervo Isquiático , Animais , Ratos , Peso Corporal , Doenças Ósseas Metabólicas/patologia , Constrição , Músculo Esquelético/patologia , Atrofia Muscular/patologia , Osteoporose/patologia , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Microtomografia por Raio-XRESUMO
Evidence exists that the gut microbiota contributes to the alterations of lipid metabolism associated with high-fat diet (HFD). Moreover, the gut microbiota has been found to modulate the metabolism and absorption of dietary lipids, thereby affecting the formation of lipoproteins occurring at the intestinal level as well as systemically, though the pathophysiological implication of altered microbiota composition in HFD and its role in the development of atherosclerotic vascular disease (ATVD) remain to be better clarified. Recently, evidence has been collected indicating that supplementation with natural polyphenols and fibres accounts for an improvement of HFD-associated intestinal dysbiosis, thereby leading to improved lipidaemic profile. This study aimed to investigate the protective effect of a bergamot polyphenolic extract (BPE) containing 48% polyphenols enriched with albedo and pulp-derived micronized fibres (BMF) in the gut microbiota of HFD-induced dyslipidaemia. In particular, rats that received an HFD over a period of four consecutive weeks showed a significant increase in plasma cholesterol, triglycerides and plasma glucose compared to a normal-fat diet (NFD) group. This effect was accompanied by body weight increase and alteration of lipoprotein size and concentration, followed by high levels of MDA, a biomarker of lipid peroxidation. Treatment with a combination of BPE plus BMF (50/50%) resulted in a significant reduction in alterations of the metabolic parameters found in HFD-fed rats, an effect associated with increased size of lipoproteins. Furthermore, the effect of BPE plus BMF treatment on metabolic balance and lipoprotein size re-arrangement was associated with reduced gut-derived lipopolysaccharide (LPS) levels, an effect subsequent to improved gut microbiota as expressed by modulation of the Gram-negative bacteria Proteobacteria, as well as Firmicutes and Bacteroidetes. This study suggests that nutraceutical supplementation of HFD-fed rats with BPE and BMP or with their combination product leads to restored gut microbiota, an effect associated with lipoprotein size re-arrangement and better lipidaemic and metabolic profiles.
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Dieta Hiperlipídica , Microbioma Gastrointestinal , Animais , Ratos , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta , Lipoproteínas , Extratos Vegetais/farmacologiaRESUMO
The maintenance of the physiological values of blood pressure is closely related to unchangeable factors (genetic predisposition or pathological alterations) but also to modifiable factors (dietary fat and salt, sedentary lifestyle, overweight, inappropriate combinations of drugs, alcohol abuse, smoking and use of psychogenic substances). Hypertension is usually characterized by the presence of a chronic increase in systemic blood pressure above the threshold value and is an important risk factor for cardiovascular disease, including myocardial infarction, stroke, micro- and macro-vascular diseases. Hypertension is closely related to functional changes in the endothelium, such as an altered production of vasoconstrictive and vasodilator substances, which lead to an increase in vascular resistance. These alterations make the endothelial tissue unresponsive to autocrine and paracrine stimuli, initially determining an adaptive response, which over time lead to an increase in risk or disease. The gut microbiota is composed of a highly diverse bacterial population of approximately 1014 bacteria. A balanced intestinal microbiota preserves the digestive and absorbent functions of the intestine, protecting from pathogens and toxic metabolites in the circulation and reducing the onset of various diseases. The gut microbiota has been shown to produce unique metabolites potentially important in the generation of hypertension and endothelial dysfunction. This review highlights the close connection between hypertension, endothelial dysfunction and gut microbiota.
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Microbioma Gastrointestinal , Hipertensão , Animais , Bactérias , Pressão Sanguínea , Disbiose/microbiologia , Humanos , Hipertensão/microbiologia , Intestinos/microbiologia , Modelos AnimaisRESUMO
In recent decades, interest in natural compounds has increased exponentially due to their numerous beneficial properties in the treatment of various acute and chronic diseases. A group of plant derivatives with great scientific interest is terpenic compounds. Among the plants richest in terpenes, the genus Ferula L. is one of the most representative, and ferutinin, the most common sesquiterpene, is extracted from the leaves, rhizome, and roots of this plant. As reported in the scientific literature, ferutinin possesses antioxidant and anti-inflammatory properties, as well as valuable estrogenic properties. Neurodegenerative and demyelinating diseases are devastating conditions for which a definite cure has not yet been established. The mechanisms involved in these diseases are still poorly understood, and oxidative stress is considered to be both a key modulator and a common denominator. In the proposed experimental system, co-cultured human neurons (SH-SY5Y) and human oligodendrocytes (MO3.13) were treated with the pro-inflammatory agent lipopolysaccharide at a concentration of 1 µg/mL for 24 h or pretreated with ferutinin (33 nM) for 24 h and subsequently exposed to lipopolysaccharide 1 µg/mL for 24 h. Further studies would, however, be needed to establish whether this natural compound can be used as a support strategy in pathologies characterized by progressive inflammation and oxidative stress phenomena.
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Benzoatos/farmacologia , Cicloeptanos/farmacologia , Inflamação/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Neurônios/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Estresse Oxidativo , Sesquiterpenos/farmacologia , Compostos Bicíclicos com Pontes/farmacologia , Linhagem Celular , Técnicas de Cocultura , Escherichia coli , Humanos , Inflamação/induzido quimicamente , Neurônios/metabolismo , Neurônios/patologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Substâncias Protetoras/farmacologiaRESUMO
The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases. In particular, we focused our attention on the role of inflammatory signaling in brown adipose tissue (BAT) thermogenic activity and the browning of white adipose tissue (WAT), which represent a relevant component of adipose alterations during obesity. Furthermore, we reported the most recent evidence in the literature on nutraceutical supplementation in the management of the adipose inflammatory state, and in particular on their potential effect on common inflammatory mediators and pathways, responsible for WAT and BAT dysfunction. Although further research is needed to demonstrate that targeting pro-inflammatory mediators improves adipose tissue dysfunction and activates thermogenesis in BAT and WAT browning during obesity, polyphenols supplementation could represent an innovative therapeutic strategy to prevent progression of obesity and obesity-related metabolic diseases.
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Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Suplementos Nutricionais , Inflamação/metabolismo , Obesidade/metabolismo , Termogênese , Adipogenia , Tecido Adiposo/metabolismo , Animais , Curcumina/química , Dieta , Retículo Endoplasmático/metabolismo , Ácidos Graxos Insaturados/metabolismo , Humanos , Resistência à Insulina , Intestinos/química , Lipídeos/química , Macrófagos/metabolismo , Polifenóis/química , Resveratrol/farmacologia , Transdução de SinaisRESUMO
Evidence has been accumulated demonstrating that heavy metals may accumulate in various organs, leading to tissue damage and toxic effects in mammals. In particular, the Central Nervous System (CNS) seems to be particularly vulnerable to cumulative concentrations of heavy metals, though the pathophysiological mechanisms is still to be clarified. In particular, the potential role of oligodendrocyte dysfunction and myelin production after exposure to subtoxic concentration I confirmed. It is ok of heavy metals is to be better assessed. Here we investigated on the effect of sub-toxic concentration of several essential (Cu2 +, Cr3 +, Ni2 +, Co2+) and non-essential (Pb2 +, Cd2+, Al3+) heavy metals on human oligodendrocyte MO3.13 and human neuronal SHSY5Y cell lines (grown individually or in co-culture). MO3.13 cells are an immortal human-human hybrid cell line with the phenotypic characteristics of primary oligodendrocytes but following the differentiation assume the morphological and biochemical features of mature oligodendrocytes. For this reason, we decided to use differentiated MO3.13 cell line. In particular, exposure of both cell lines to heavy metals produced a reduced cell viability of co-cultured cell lines compared to cells grown separately. This effect was more pronounced in neurons that were more sensitive to metals than oligodendrocytes when the cells were grown in co-culture. On the other hand, a significant reduction of lipid component in cells occurred after their exposure to heavy metals, an effect accompanied by substantial reduction of the main protein that makes up myelin (MBP) in co-cultured cells. Finally, the effect of heavy metals in oligodendrocytes were associated to imbalanced intracellular calcium ion concentration as measured through the fluorescent Rhod-2 probe, thus confirming that heavy metals, even used at subtoxic concentrations, lead to dysfunctional oligodendrocytes. In conclusion, our data show, for the first time, that sub-toxic concentrations of several heavy metals lead to dysfunctional oligodendrocytes, an effect highlighted when these cells are co-cultured with neurons. The pathophysiological mechanism(s) underlying this effect is to be better clarified. However, imbalanced intracellular calcium ion regulation, altered lipid formation and, finally, imbalanced myelin formation seem to play a major role in early stages of heavy metal-related oligodendrocyte dysfunction.
Assuntos
Metais Pesados/toxicidade , Proteína Básica da Mielina/metabolismo , Neurônios/metabolismo , Oligodendroglia/metabolismo , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular , Sistema Nervoso Central , Humanos , Metais Pesados/química , Bainha de Mielina/metabolismo , Neurogênese/efeitos dos fármacos , Neurônios/química , Neurônios/efeitos dos fármacos , Neurônios/patologia , Oligodendroglia/química , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/patologiaRESUMO
Neurodegenerative diseases (NDs) affect millions of people worldwide, and to date, Alzheimer's and Parkinson's diseases are the most common NDs. Of the many risk factors for neurodegeneration, the aging process has the most significant impact, to the extent that it is tempting to consider neurodegenerative disease as a manifestation of accelerated aging. However, genetic and environmental factors determine the course of neurodegenerative disease progression. It has been proposed that environmental stimuli influence neuroplasticity. Some clinical studies have shown that healthy lifestyles and the administration of nutraceuticals containing bioactive molecules possessing antioxidant and anti-inflammatory properties have a preventive impact or mitigate symptoms in previously diagnosed patients. Despite ongoing research efforts, the therapies currently used for the treatment of NDs provide only marginal therapeutic benefits; therefore, the focus is now directly on the search for natural products that could be valuable tools in combating these diseases, including the natural compound Andrographis paniculata (Ap) and its main constituent, andrographolide (Andro). Preclinical studies have shown that the aqueous extract of Ap can modulate neuroinflammatory and neurodegenerative responses, reducing inflammatory markers and oxidative stress in various NDs. Therefore, in this review, we will focus on the molecular mechanisms by which Ap and Andro can modulate the processes of neurodegeneration and neuroinflammation, which are significant causes of neuronal death and cognitive decline.
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Andrographis , Doenças Neurodegenerativas , Humanos , Andrographis paniculata , Doenças Neuroinflamatórias , Doenças Neurodegenerativas/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
Ferula L., belonging to the Apiaceae family, is represented by about 170 species predominantly present in areas with a mild-warm-arid climate, including the Mediterranean region, North Africa and Central Asia. Numerous beneficial activities have been reported for this plant in traditional medicine, including antidiabetic, antimicrobial, antiproliferative, anti-dysentery, stomachache with diarrhea and cramps remedies. FER-E was obtained from the plant F. communis, and precisely from the root, collected in Sardinia, Italy. A total of 25 g of root was mixed with 125 g of acetone (ratio 1:5, room temperature). The solution was filtered, and the liquid fraction was subjected to high pressure liquid chromatographic separation (HPLC). In particular, 10 mg of dry root extract powder, from F. communis, was dissolved in 10.0 mL of methanol, filtered with a 0.2 µm PTFE filter and subjected to HPLC analysis. The net dry powder yield obtained was 2.2 g. In addition, to reduce the toxicity of FER-E, the component ferulenol was removed. High concentrations of FER-E have demonstrated a toxic effect against breast cancer, with a mechanism independent of the oxidative potential, which is absent in this extract. In fact, some in vitro tests were used and showed little or no oxidizing activity by the extract. In addition, we appreciated less damage on the respective healthy cell lines (breast), assuming that this extract could be used for its potential role against uncontrolled cancer growth. The results of this research have also shown that F. communis extract could be used together with tamoxifen, increasing its effectiveness, and reducing side effects. However, further confirmatory experiments should be carried out.
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Olea europaea L. is a plant belonging to the Oleaceae family, widely grown around the Mediterranean Basin and its leaves are a source of phenolic compounds with antioxidant and anti-inflammatory capacity. Among these, oleuropein and luteolin-7-O-glucoside represent two major polyphenolic compounds in olive-leaf extract. Herein, a polystyrene resin was used to recover the polyphenolic fraction from the acetone-water leaf extract from Nocellara del Belice cultivar, which showed the higher level of analysed bioactive compounds, compared to Carolea cultivar. The antioxidant activity of the extract concentrated in phenolic compounds (OLECp) was evaluated through a classical assay and electron paramagnetic resonance (EPR) for DPPH and hydroxyl radicals scavenging. Thus, the anti-inflammatory activity and the potential beneficial effects in reducing lipid accumulation in an in vitro model of NAFLD using McA-RH7777 cells exposed to oleic acid (OA) were evaluated. Nile Red and Oil Red O have been used to stain the lipid accumulation, while the inflammatory status was assessed by Cytokines Bioplex Assay. OLECp (TPC: 92.93 ± 9.35 mg GAE/g, TFC: 728.12 ± 16.04 mg RE/g; 1 g of extract contains 315.250 mg of oleuropein and 17.44 mg of luteolin-7-O-glucoside) exerted a good radical scavenging capability (IC50: 2.30 ± 0.18 mg/mL) with a neutralizing power against DPPH and hydroxyl radicals, as confirmed by the decreased signal area of the EPR spectra. Moreover, OLECp at concentration of 25, 50 and 100 µg/mL counteracted the intracellular inflammatory status, as result of decreased intracellular lipid content. Our results highlighted the multiple properties and applications of an O. europaea extract concentrated in polyphenols, and the possibility to formulate novel nutraceuticals with antioxidant properties, destined to ameliorate human health.
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Ferula communis L. (F. communis) belongs to the Apiaceae family and is a herbaceous plant with various pharmaceutical properties, due to the different contents of bioactive compounds extracted mainly from its roots, as well as its leaves and rhizome. To date, this plant extract has demonstrated estrogenic, anti-inflammatory, antiproliferative, cytotoxic, antimicrobial and anti-neoplastic properties. Its estrogenic activity is justified by the presence of ferutinin, an ester of a sesquiterpenic alcohol that acts as an agonist for estrogen receptors, with a chemical formula equal to C22H3O4. The component present in F. communis responsible for the toxicity of the plant is ferulenol, a prenylated coumarin with the chemical formula C24H30O3. This compound is capable of inducing mortality via its strong anti-coagulant properties, leading to a lethal hemorrhagic syndrome, ferulosis, in animals that feed on a chemotype of F. communis containing a high amount of ferulenol. The removal of the component ferulenol makes extracts of Ferula non-toxic. In fact, the remaining prenylated coumarins are not present in concentrations sufficient to induce toxicity. The intake of high concentrations of the extract of this plant leads a double dose-dependent effect that is typical of sesquiterpenes such as ferutinin. Here, we assessed the cytotoxicity and the estrogenic properties of the F. communis phytocomplex obtained through extraction using a mixture of acetone and water. Among the active constituents of F. communis, the identification of ferutinin and ferulenol was performed using HPLC. The effects of the extract were evaluated, following the removal of ferulenol, on three cell lines: human breast cancer MCF-7, human cervical cancer HeLa and human osteoblastic sarcoma Saos-2. The choice of these cell lines was justified by the need to mimic certain processes which may occur in vivo and which are estrogen-dependent. The obtained results demonstrated that F. communis extract, in addition to possessing an estrogenic-like property, showed a dose-dependent effect. Low concentrations (0.1-0.8 µM) demonstrated a hyperproliferative effect, whereas higher concentrations (1.6-50 µM) were toxic. Therefore, this extract could be an excellent candidate to make up for a reduction or lack of estrogen.
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Diabetes is a complex chronic disease, and among the affected patients, cardiovascular disease (CVD)is the most common cause of death. Consequently, the evidence for the cardiovascular benefit of glycaemic control may reduce long-term CVD rates. Over the years, multiple pharmacological approaches aimed at controlling blood glucose levels were unable to significantly reduce diabetes-related cardiovascular events. In this view, a therapeutic strategy combining SGLT2 inhibitors and plant extracts might represent a promising solution. Indeed, countering the main cardiometabolic risk factor using plant extracts could potentiate the cardioprotective action of SGLT2 inhibitors. This review highlights the main molecular mechanisms underlying these beneficial effects that could contribute to the better management of diabetic patients.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Glicemia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Transportador 2 de Glucose-Sódio/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêuticoRESUMO
Doxorubicin is an anthracycline that is commonly used as a chemotherapy drug due to its cytotoxic effects. The clinical use of doxorubicin is limited due to its known cardiotoxic effects. Treatment with anthracyclines causes heart failure in 15-17% of patients, resulting in mitochondrial dysfunction, the accumulation of reactive oxygen species, intracellular calcium dysregulation, the deterioration of the cardiomyocyte structure, and apoptotic cell death. Polyphenols have a wide range of beneficial properties, and particular importance is given to Bergamot Polyphenolic Fraction; Oleuropein, one of the main polyphenolic compounds of olive oil; and Cynara cardunculus extract. These natural compounds have particular beneficial characteristics, owing to their high polyphenol contents. Among these, their antioxidant and antoproliferative properties are the most important. The aim of this paper was to investigate the effects of these three plant derivatives using an in vitro model of cardiotoxicity induced by the treatment of rat embryonic cardiomyoblasts (H9c2) with doxorubicin. The biological mechanisms involved and the crosstalk existing between the mitochondria and the endoplasmic reticulum were examined. Bergamot Polyphenolic Fraction, Oleuropein, and Cynara cardunculus extract were able to decrease the damage induced by exposure to doxorubicin. In particular, these natural compounds were found to reduce cell mortality and oxidative damage, increase the lipid content, and decrease the concentration of calcium ions that escaped from the endoplasmic reticulum. In addition, the direct involvement of this cellular organelle was demonstrated by silencing the ATF6 arm of the Unfolded Protein Response, which was activated after treatment with doxorubicin.
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Cardiotoxicidade/tratamento farmacológico , Cynara/química , Doxorrubicina/efeitos adversos , Olea/química , Extratos Vegetais/farmacologia , Animais , Antraciclinas , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Suplementos Nutricionais , Glucosídeos Iridoides , Mitocôndrias , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo , Polifenóis/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Doxorubicin (Doxo) is a widely used antineoplastic drug which often induces cardiomyopathy, leading to congestive heart failure through the intramyocardial production of reactive oxygen species (ROS). Icariin (Ica) is a flavonoid isolated from Epimedii Herba (Berberidaceae). Some reports on the pharmacological activity of Ica explained its antioxidant and cardioprotective effects. The aim of our study was to assess the protective activities of Ica against Doxo-detrimental effects on rat heart-tissue derived embryonic cardiac myoblasts (H9c2 cells) and to identify, at least in part, the molecular mechanisms involved. Our results showed that pretreatment of H9c2 cells with 1 µM and 5 µM of Ica, prior to Doxo exposure, resulted in an improvement in cell viability, a reduction in ROS generation, the prevention of mitochondrial dysfunction and mPTP opening. Furthermore, for the first time, we identified one feasible molecular mechanism through which Ica could exerts its cardioprotective effects. Indeed, our data showed a significant reduction in Caveolin-1(Cav-1) expression levels and a specific inhibitory effect on phosphodiesterase 5 (PDE5a) activity, improving mitochondrial function compared to Doxo-treated cells. Besides, Ica significantly prevented apoptotic cell death and downregulated the main pro-autophagic marker Beclin-1 and LC3 lipidation rate, restoring physiological levels of activation of the protective autophagic process. These results suggest that Ica might have beneficial cardioprotective effects in attenuating cardiotoxicity in patients requiring anthracycline chemotherapy through the inhibition of oxidative stress and, in particular, through the modulation of Cav-1 expression levels and the involvement of PDE5a activity, thereby leading to cardiac cell survival.
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Cardiotoxicidade/prevenção & controle , Caveolina 1/metabolismo , Flavonoides/farmacologia , Mioblastos Cardíacos/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Autofagia/efeitos dos fármacos , Cardiotoxicidade/etiologia , Doxorrubicina , Estresse Oxidativo/efeitos dos fármacos , Ratos , Regulação para Cima/efeitos dos fármacosRESUMO
Aims of the current study were to explore differences in coping between 58 patients with schizoaffective disorder (SAD) and 89 with schizophrenia (SZ) and to identify factors associated with coping in both disorders. The demographic and clinical characteristics of patients with SAD and with SZ were compared using ANOVA and χ(2). Pearson's correlations were calculated between coping styles and socio-demographic and clinical variables in each group. The significant ones were subsequently analyzed using multiple regressions. Patients with SAD used emotion oriented coping more frequently than patients 2016with SZ. In patients with SAD, self-esteem contributed to task-oriented; avolition-anhedonia (AA) to emotion-oriented; duration of illness and years of education to distraction; AA to social diversion. In patients with SZ, AA, the mental component summary score of the Short Form - 36 Health Survey (SF-36) and self-esteem contributed to emotion oriented coping; the mental component summary score of SF-36 to distraction; AA to social diversion. Our results suggest that patients with SAD and SZ use diverse coping strategies. A greater attention must be given to the presence of self-esteem and AA in individuals with both disorders. These factors are potentially modifiable from specific therapeutic interventions, which can produce effects on coping strategies.
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Adaptação Psicológica , Transtornos Psicóticos/psicologia , Esquizofrenia , Psicologia do Esquizofrênico , Adulto , Anedonia , Emoções , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , AutoimagemRESUMO
AIM: The aim of this study was to investigate cognitive functioning and insight of illness in two groups of patients during their stable phases, one with schizophrenia and one with schizoaffective disorder. METHODS: We recruited 104 consecutive outpatients, 64 with schizophrenia, 40 with schizoaffective disorder, in the period between July 2010 and July 2011. They all fulfilled formal Diagnostic and Statistical Manual of Mental disorders (DSM-IV-TR) diagnostic criteria for schizophrenia and schizoaffective disorder. Psychiatric assessment included the Clinical Global Impression Scale-Severity (CGI-S), the Positive and Negative Sindrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Global Assessment of Functioning (GAF). Insight of illness was evaluated using SUMD. Neuropsychological assessment included Winsconsin Card Sorting Test (WCST), California Verbal Learning Test (CVLT), Stroop Test and Trail Making Test (TMT). Differences between the groups were tested using Chi-square test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. All variables significantly different between the two groups of subjects were subsequently analysed using a logistic regression with a backward stepwise procedure using diagnosis (schizophrenia/schizoaffective disorder) as dependent variable. RESULTS: After backward selection of variables, four variables predicted a schizoaffective disorder diagnosis: marital status, a higher number of admission, better attentive functions and awareness of specific signs or symptoms of disease. The prediction model accounted for 55% of the variance of schizoaffective disorder diagnosis. DISCUSSION: With replication, our findings would allow higher diagnostic accuracy and have an impact on clinical decision making, in light of an amelioration of vocational functioning.