RESUMEN

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders worldwide. It is caused by the degeneration of dopaminergic neurons from the substantia nigra pars compacta. This neuronal loss causes the dopamine deficiency that leads to a series of functional changes within the basal ganglia, producing motor control abnormalities. L-DOPA is considered the gold standard for PD treatment, and it may alleviate its clinical manifestations for some time. However, its prolonged administration produces tolerance and several severe side effects, including dyskinesias and gastrointestinal disorders. Thus, there is an urgent need to find effective medications, and current trends have proposed some natural products as emerging options for this purpose. Concerning this, curcumin represents a promising bioactive compound with high therapeutic potential. Diverse studies in cellular and animal models have suggested that curcumin could be employed for the treatment of PD. Therefore, the objective of this narrative mini-review is to present an overview of the possible therapeutic effects of curcumin and the subjacent molecular mechanisms. Moreover, we describe several possible nanocarrier-based approaches to improve the bioavailability of curcumin and enhance its biological activity.

Asunto(s)

Encéfalo/efectos de los fármacos , Curcumina/administración & dosificación , Nanopartículas/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Disponibilidad Biológica , Encéfalo/metabolismo , Curcumina/química , Curcumina/farmacocinética , Liberación de Fármacos , Glutatión Peroxidasa/metabolismo , Humanos , NADPH Oxidasas/antagonistas & inhibidores , NADPH Oxidasas/metabolismo , Nanopartículas/química , Fármacos Neuroprotectores/administración & dosificación , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacocinética , Enfermedad de Parkinson/metabolismo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Resultado del Tratamiento , Regulación hacia Arriba/efectos de los fármacos

RESUMEN

Furazolidone (FZD) is a widely used drug in human and veterinary medicine, and has antibacterial and antiprotozoal action. Although it is widely used as a therapy in various pathological conditions, studies on the efficacy of FZD associated with immune responses are still limited. In this review, we seek to describe which immunopharmacological responses are caused by the administration of FZD. The study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A systematic review of clinical trials and in vitro and in vivo experimental studies was carried out, which resulted in 943 papers, of which 35 were considered eligible and, of these 35, 4 were selected for analysis. The studies listed indicated that administration of FZD can modulate pro- or anti-inflammatory pathways, with a probable increase in the expression of reactive oxygen species and a modulation of apoptotic pathways.

Asunto(s)

Inmunidad Adaptativa/inmunología , Antiinfecciosos Locales/farmacología , Apoptosis/inmunología , Furazolidona/farmacología , Inmunidad Innata/inmunología , Inmunidad Adaptativa/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Humanos , Inmunidad Innata/efectos de los fármacos , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/inmunología , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

Astrocytes are crucial for the maintenance of brain homeostasis by actively participating in the metabolism of glucose, which is the main energy substrate for the central nervous system (CNS), in addition to other supportive functions. More specifically, astrocytes support neurons through the metabolic coupling of synaptic activity and glucose utilization. As such, diabetes mellitus (DM) and consequent glucose metabolism disorders induce astrocyte damage, affecting CNS functionality. Glioprotective molecules can promote protection by improving glial functions and avoiding toxicity in different pathological conditions, including DM. Therefore, this review discusses specific pathomechanisms associated with DM/glucose metabolism disorder-induced gliotoxicity, namely astrocyte metabolism, redox homeostasis/mitochondrial activity, inflammation, and glial signaling pathways. Studies investigating natural products as potential glioprotective strategies against these deleterious effects of DM/glucose metabolism disorders are also reviewed herein. These products include carotenoids, catechins, isoflavones, lipoic acid, polysaccharides, resveratrol, and sulforaphane.

Asunto(s)

Astrocitos/efectos de los fármacos , Encéfalo/metabolismo , Diabetes Mellitus/metabolismo , Glucosa/antagonistas & inhibidores , Estrés Oxidativo/efectos de los fármacos , Animales , Astrocitos/metabolismo , Encéfalo/efectos de los fármacos , Diabetes Mellitus/tratamiento farmacológico , Glucosa/metabolismo , Humanos , Isoflavonas/administración & dosificación , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Resveratrol/administración & dosificación , Ácido Tióctico/administración & dosificación

RESUMEN

SUMMARY: A large body of evidence supports the protective role of the flavonol antioxidant compound quercetin in mammals. We tested the hypothesis that quercetin can protect against the hypothalamus-pituitary-gonadal (HPG) axis defect like a reduction in gonadotropins and testicular hormones and abnormal semen analysis induced by chronic unpredictable stress (CUS), possibly via the downregulation of oxidative stress (ROS) and p53-Bax-caspase-3 pathways. Rats were either exposed to a variety of unpredictable stressors daily before being sacrificed after 3 weeks (model group) or were treated with quercetin (50 mg/kg body weight/day) at the same time the CUS were induced (treated group). Harvested testicular tissues were stained with basic histological staining, and testis homogenates were assayed for the tumor suppressor p53, apoptosis regulator Bax, B-cell lymphoma 2 (Bcl-2), caspase-3, malondialdehyde (MDA), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, harvested epididymis tissues were used to assess semen analysis, and blood samples were assayed for the testicular hormone testosterone, the adrenal cortex hormone corticosterone, and the anterior pituitary gonadotropins, follicular stimulating hormone (FSH) and luteinizing hormone (LH). CUS induced profound testicular damage and significantly (p<0.05) induced p53, Bax, caspase-3, MDA, and corticosterone, which were significantly (p<0.05) inhibited by quercetin except corticosterone. Whereas, quercetin significantly (p<0.05) increased FSH, LH, testosterone, Bcl-2, GPx, and SOD levels that were inhibited by CUS. In addition, CUS induced oligozoospermia, asthenozoospermia, and teratozoospermia, which were significantly (p<0.05) protected by quercetin. Thus, Quercetin protects against CUS-induced HPG defects in rats, which is associated with the inhibition of ROS-p53-Bax-caspase-3 axis.

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RESUMEN: El papel protector del compuesto antioxidante flavonol quercetina en los mamíferos ha sido ampliamente reportado. Probamos la hipótesis que la quercetina puede proteger contra el defecto del eje hipotálamo-hipofisiario- gonadal (HHG) como una reducción de gonadotropinas y hormonas testiculares y análisis de semen anormal inducido por estrés crónico impredecible (ECI), posiblemente a través de la regulación reducida del estrés oxidativo (REO) y las vías p53- Bax-caspasa-3. Las ratas fueron expuestas a una variedad de fac- tores estresantes impredecibles diariamente antes de ser sacrificadas después de 3 semanas (grupo modelo) o fueron tratadas con quercetina (50 mg / kg de peso corporal / día) al mismo tiempo que se indujo la ECI (grupo tratado). Los tejidos testiculares fueron teñidos con tinción histológica básica y los homogeneizados de testículo se analizaron para determinar el supresor de tumores p53, el regulador de apoptosis Bax, el linfoma de células B 2 (Bcl-2), la caspasa-3, el malondialdehído (MDA), la glutatión peroxidasa (GPx) y superóxido dismutasa (SOD). Además, se utilizaron tejidos del epidídimo recolectados para evaluar el análisis de semen y se analizaron muestras de sangre para determinar la hormona testicular testosterona, la hormona corticosterona de la corteza suprarrenal y las gonadotropinas de la hipófisis anterior, la hormona estimulante folicular (FSH) y la hormona luteinizante (LH). El ECI indujo daño testicular importante e indujo significativamente niveles de (p <0,05) p53, Bax, caspasa-3, MDA y corticosterona, que fueron inhibidos (p <0,05) por la quercetina. La quercetina aumentó significativamente (p <0,05) los niveles de FSH, LH, testosterona, Bcl-2, GPx y SOD que fueron inhibidos por ECI. Además, ECI indujo oligozoospermia, astenozoospermia y teratozoospermia, protegidos de manera significativa (p <0,05) por la quercetina. Por lo tanto, la quercetina protege contra los defectos de HHG inducidos por ECI en ratas, lo que está asociado con la inhibición del eje ROS-p53-Bax-caspasa-3.

Asunto(s)

Animales , Masculino , Ratas , Quercetina/administración & dosificación , Estrés Fisiológico , Enfermedades Testiculares/etiología , Testículo/efectos de los fármacos , Antioxidantes/administración & dosificación , Testículo/lesiones , Enfermedad Crónica , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Ratas Wistar , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Proteína X Asociada a bcl-2/antagonistas & inhibidores , Caspasa 3/efectos de los fármacos , Eje Hipotálamico-Pituitario-Gonadal/efectos de los fármacos

RESUMEN

Hypertension is a risk factor for erectile dysfunction (ED) and both conditions are associated with oxidative stress. Given that nitrite is described to display antioxidant effects, we hypothesized that treatment with nitrite would exert antioxidant effects attenuating both reactive oxygen species (ROS) generation in the corpora cavernosa (CC) and ED induced by hypertension. Two kidney, one clip (2K1C) hypertension was induced in male Wistar rats. Treatment with sodium nitrite (15 mg/kg/day, p.o., gavage) was initiated two weeks after surgery to induce hypertension and maintained for four weeks. Nitrite abrogated both the decrease in intracavernosal pressure and endothelial dysfunction of the CC induced by hypertension. Treatment with nitrite decreased hypertension-induced ROS generation in the CC assessed in situ using the fluorescent dye dihidroethidium (DHE) and with the lucigenin assay. Western immunoblotting analysis revealed that nitrite prevented the increase in Nox1 expression in the CC from 2K1C rats. Decreased concentrations of hydrogen peroxide (H2O2) were found in the CC from hypertensive rats and treatment with nitrite prevented this response. Treatment with nitrite increased the fluorescence of DAF-2DA in the CC from sham-operated rats and restored nitric oxide (NO) levels in the CC from 2K1C rats. In summary, we found novel evidence that nitrite reversed the decrease in intracavernosal pressure induced by 2K1C hypertension. This response was partially attributed to the antioxidant effect of nitrite that blunted ROS generation and endothelial dysfunction in the CC. In addition, nitrite-derived NO may have promoted direct protective actions against hypertension-induced CC dysfunction.

Asunto(s)

Disfunción Eréctil/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Pene/efectos de los fármacos , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Animales , Antihipertensivos , Antioxidantes , Disfunción Eréctil/metabolismo , Hipertensión/metabolismo , Masculino , Nitritos , Pene/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

BACKGROUND: In general, fungal species are characterized by their opportunistic character and can trigger various infections in immunocompromised hosts. The emergence of infections associated with high mortality rates is due to the resistance mechanisms that these species develop. METHODS: This phenomenon of resistance denotes the need for the development of new and effective therapeutic approaches. In this paper, we report the investigation of the antioxidant and antifungal behavior of dimeric naphthoquinones derived from lawsone whose antimicrobial and antioxidant potential has been reported in the literature. RESULTS: Seven fungal strains were tested, and the antioxidant potential was tested using the combination of the methodologies: reducing power, total antioxidant capacity and cyclic voltammetry. Molecular docking studies (PDB ID 5V5Z and 1EA1) were conducted which allowed the derivation of structureactivity relationships (SAR). Compound 1-i, derived from 3-methylfuran-2-carbaldehyde showed the highest antifungal potential with an emphasis on the inhibition of Candida albicans species (MIC = 0.5 µg/mL) and the highest antioxidant potential. CONCLUSION: A combination of molecular modeling data and in vitro assays can help to find new solutions to this major public health problem.

Asunto(s)

Antifúngicos/farmacología , Antioxidantes/farmacología , Candida albicans/efectos de los fármacos , Simulación del Acoplamiento Molecular , Naftoquinonas/farmacología , Teoría Cuántica , Antifúngicos/síntesis química , Antifúngicos/química , Antioxidantes/síntesis química , Antioxidantes/química , Reparación del ADN , Dimerización , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Naftoquinonas/síntesis química , Naftoquinonas/química , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad

RESUMEN

Recently, cardiotonic steroids (CTS) have been shown to lead to the activation of Na,K-ATPase at low concentrations in brain, promoting neuroprotection against ischemia. We report here the results of the use of digoxin and its semisynthetic derivatives BD-14, BD-15, and BD-16 against partial chemical ischemic induction followed by reperfusion in murine neuroblastoma cells neuro-2a (N2a). For chemical ischemic induction, sodium azide (5 mM) was used for 5 hours, and then reperfusion was induced for 24 hours. Na,K-ATPase activity and protein levels were analyzed in membrane preparation of N2a cells pretreated with the compounds (150 nM), in the controls and in induced chemical ischemia. In the Na,K-ATPase activity and protein levels assays, the steroids digoxin and BD-15 demonstrated a capacity to modulate the activity of the enzyme directly, increasing its levels of expression and activity. Oxidative parameters, such as superoxide dismutase (SOD) activity, lipid peroxidation (thiobarbituric acid reactive substance), glutathione peroxidase (GPx), glutathione (GSH) levels, hydrogen peroxide content, and the amount of free radicals (reactive oxygen species) during induced chemical ischemia were also evaluated. Regarding the redox state, lipid peroxidation, hydrogen peroxide content, and GPx activity, we have observed an increase in the chemical ischemic group, and a reduction in the groups treated with CTS. SOD activity increased in all treated groups when compared to control and GSH levels decreased when treated with sodium azide and did not change with CTS treatments. Regarding the lipid profile, we saw a decrease in the content of phospholipids and cholesterol in the chemical ischemic group, and an increase in the groups treated with CTS. In conclusion, the compounds used in this study demonstrate promising results, since they appear to promote neuroprotection in cells exposed to chemical ischemia.

Asunto(s)

Digoxina/farmacología , Expresión Génica/efectos de los fármacos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Animales , Isquemia Encefálica/prevención & control , Células CACO-2 , Hipoxia de la Célula/efectos de los fármacos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Colesterol/metabolismo , Digoxina/análogos & derivados , Digoxina/síntesis química , Glutatión/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Humanos , Peroxidación de Lípido/efectos de los fármacos , Ratones , Modelos Biológicos , Neuronas/metabolismo , Neuronas/patología , Fármacos Neuroprotectores/síntesis química , Estrés Oxidativo/efectos de los fármacos , Fosfolípidos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Azida Sódica/antagonistas & inhibidores , Azida Sódica/farmacología , ATPasa Intercambiadora de Sodio-Potasio/genética , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo

RESUMEN

INTRODUCTION: Neurodegenerative diseases (NDDs) are progressive, directly affecting the central nervous system (CNS), the most common and recurrent are Alzheimer's disease (AD) and Parkinson's disease (PD). One factor frequently mentioned in the etiology of NDDs is the generation of free radicals and oxidative stress, producing cellular damages. Studies have shown that the consumption of foods rich in polyphenols, especially those of the flavonoid class, has been related to the low risk in the development of several diseases. Due to the antioxidant properties present in the food, a fruit that has been gaining prominence among these foods is the Euterpe oleracea Mart. (açaí), because it presents in its composition significant amounts of a subclass of the flavonoids, the anthocyanins. METHODS: In the case review, the authors receive a basic background on the most common NDDs, oxidative stress and antioxidants. In addition, revisiting the various studies related to NDDs, including flavonoids and consumption of açaí. RESULTS: Detailed analysis of the recently reported case studies reveal that dietary consumption of flavonoid-rich foods, such as açaí fruits, suggests the efficacy to attenuate neurodegeneration and prevent or reverse the age-dependent deterioration of cognitive function. CONCLUSION: This systematic review points out that flavonoids presenting in açaí have the potential for the treatment of diseases such as PD and AD and are candidates for drugs in future clinical research. However, there is a need for in vitro and in vivo studies with polyphenol that prove and ratify the therapeutic potential of this fruit for several NDDs.

Asunto(s)

Antioxidantes/uso terapéutico , Euterpe , Flavonoides/uso terapéutico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Animales , Antioxidantes/química , Antioxidantes/farmacología , Flavonoides/química , Flavonoides/farmacología , Humanos , Enfermedades Neurodegenerativas/metabolismo , Estrés Oxidativo/fisiología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Resultado del Tratamiento

RESUMEN

PURPOSE: Management of male infertility is always a difficult task, with pathophysiology and available treatments often poorly understood. The purpose of this review was to summarize current evidence regarding the use of protective agents against reactive oxygen species (ROS), such as antioxidants that may be useful in the treatment of male factor infertility. METHODS: For this publication, a search of studies concerning oxidative stress, male infertility and antioxidant therapy was performed using the search engines ScienceDirect, OVID, PubMed and MEDLINE. Articles published in languages other than English were not considered. RESULTS: An interest in the physiologic and pathologic effects of ROS has grown. Nevertheless, use of antioxidants is challenging, considering the balance between physiological ROS activity and detrimental oxidative stress level. Several studies have shown positive outcomes in terms of semen parameters, with others having failed to do so. Available evidence is still limited in pregnancy and live birth rates. CONCLUSIONS: Protective agents against ROS, such as antioxidants, may have positive effects on semen parameters in some patients, although a widespread indication is still restricted by practical aspects, including unknown physiological levels of ROS and controversy regarding different concentrations and combinations of drugs.

Asunto(s)

Antioxidantes/uso terapéutico , Infertilidad Masculina/tratamiento farmacológico , Infertilidad Masculina/metabolismo , Estrés Oxidativo , Humanos , Masculino , Especies Reactivas de Oxígeno/antagonistas & inhibidores

RESUMEN

Jabuticaba has a high concentration of phenolic compounds, which have a significant antioxidant capacity. Methodologies have been developed to evaluate the ability of plant extracts to fight free radicals such as H2O2, O2•-, HOCl, ONOO- and ROO•. Thus, the capacity of deactivation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in peel and seed extracts of five varieties of jabuticaba was evaluated. Sabará peel (SFP) deactivated HOCl with IC50 9.24 µg. mL-1; Paulista seed (PF) deactivated O2•- with IC50 16.15 µg. mL-1; Coroada seed (CFP) deactivated ONOO- with IC50 3.84 µg. mL-1; the peel of CFP deactivated ONOO- with IC50 5.88 µg. mL-1; the peel of SFP deactivated the ROO• at 918.16 µmol TE. g-1; and Sabará seed deactivated H2O2 with 49.11% inhibition at a concentration of 125 µg. mL-1 of extract. These results demonstrate the high antioxidant potential of this fruit, indicating that it could be extremely beneficial to human health.

Asunto(s)

Antioxidantes/farmacología , Myrtaceae/química , Extractos Vegetales/farmacología , Especies de Nitrógeno Reactivo/antagonistas & inhibidores , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Frutas/química , Humanos , Extractos Vegetales/química , Semillas/química

RESUMEN

Any spinal cord injury carries the potential for persistent disability affecting motor, sensory and autonomic functions. To prevent this outcome, it is highly desirable to block a chain of deleterious reactions developing in the spinal areas immediately around the primary lesion. Thus, early timing of pharmacological neuroprotection should be one major strategy whose impact may be first studied with preclinical models. Using a simple in vitro model of the rat spinal cord it is possible to mimic pathological processes like excitotoxicity that damages neurons because of excessive glutamate receptor activation due to injury, or hypoxic/dysmetabolic insult that preferentially affects glia following vascular dysfunction. While ongoing research is exploring the various components of pathways leading to cell death, current treatment principally relies on the off-label use of riluzole (RLZ) or methylprednisolone sodium succinate (MPSS). The mechanism of action of these drugs is diverse as RLZ targets mainly neurons and MPSS targets glia. Even when applied after a transient excitotoxic stimulus, RLZ can provide effective prevention of secondary excitotoxic damage to premotoneurons, although not to motoneurons that remain very vulnerable. This observation indicates persistent inability to express locomotor activity despite pharmacological treatment conferring some histological protection. MPSS can protect glia from dysmetabolic insult, yet it remains poorly effective to prevent neuronal death. In summary, it appears that these pharmacological agents can produce delayed protection for certain cell types only, and that their combined administration does not provide additional benefit. The search should continue for better, mechanism-based neuroprotective agents.

Asunto(s)

Antiinflamatorios/uso terapéutico , Metilprednisolona/uso terapéutico , Neuroprotección/fisiología , Fármacos Neuroprotectores/uso terapéutico , Riluzol/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Humanos , Metilprednisolona/farmacología , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Riluzol/farmacología , Traumatismos de la Médula Espinal/metabolismo

RESUMEN

As espécies reativas de oxigênio (EROs) são radicais livres derivadas do oxigênio. O fármaco Alopurinol (ALO) possui um efeito inibidor da enzima Xantina Oxidase, uma das vias da produção de EROs. Para combater esse ataque oxidativo no nosso organismo, existe uma defesa antioxidante enzimática, composta pelas enzimas Superóxido dismutase (SOD), Catalase (CAT) e Glutationa Peroxidase (GPX). O objetivo do presente estudo foi analisar os efeitos do alopurinol na defesa antioxidante no fígado de ratos Wistar. Foram utilizados 20 ratos machos divididos em dois grupos: Controle (C) e Alopurinol (ALO). A droga foi administrada para os animais do grupo ALO, enquanto que no grupo C houve uma administração de veículo (salina), ambos durante 3 dias. Os resultados apontaram uma redução significativa na atividade das enzimas antioxidantes no grupo ALO em comparação ao grupo C. A partir desses resultados sugeriu-se que o alopurinol foi eficiente na inibição de EROs.

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Reactive oxygen species (ROS) are free radicals derived from oxygen. The drug Allopurinol (ALO) has an inhibitory effect of the enzyme Xanthine Oxidase, one of the routes of ROS production. To combat this oxidative attack in our body, there is an enzymatic antioxidant defense, composed by the enzymes Superoxide dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPX). The aim of the present study was to analyze the effects of allopurinol on the antioxidant defense in the liver of Wistar rats. Twenty male rats were divided into two groups: Control (C) and Allopurinol (ALO). The drug was administered to the animals of the ALO group, while in group C there was a vehicle (saline) administration, both for 3 days. The results indicated a significant reduction in the activity of the antioxidant enzymes in the ALO group compared to the group C. From these results it was suggested that allopurinol was efficient in inhibiting ROS.

Asunto(s)

Masculino , Animales , Ratas , Alopurinol/administración & dosificación , Alopurinol/uso terapéutico , Antioxidantes , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Hígado , Ratas Wistar/metabolismo

RESUMEN

As espécies reativas de oxigênio (EROs) são radicais livres derivadas do oxigênio. O fármaco Alopurinol (ALO) possui um efeito inibidor da enzima Xantina Oxidase, uma das vias da produção de EROs. Para combater esse ataque oxidativo no nosso organismo, existe uma defesa antioxidante enzimática, composta pelas enzimas Superóxido dismutase (SOD), Catalase (CAT) e Glutationa Peroxidase (GPX). O objetivo do presente estudo foi analisar os efeitos do alopurinol na defesa antioxidante no fígado de ratos Wistar. Foram utilizados 20 ratos machos divididos em dois grupos: Controle (C) e Alopurinol (ALO). A droga foi administrada para os animais do grupo ALO, enquanto que no grupo C houve uma administração de veículo (salina), ambos durante 3 dias. Os resultados apontaram uma redução significativa na atividade das enzimas antioxidantes no grupo ALO em comparação ao grupo C. A partir desses resultados sugeriu-se que o alopurinol foi eficiente na inibição de EROs.(AU)

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Reactive oxygen species (ROS) are free radicals derived from oxygen. The drug Allopurinol (ALO) has an inhibitory effect of the enzyme Xanthine Oxidase, one of the routes of ROS production. To combat this oxidative attack in our body, there is an enzymatic antioxidant defense, composed by the enzymes Superoxide dismutase (SOD), Catalase (CAT) and Glutathione Peroxidase (GPX). The aim of the present study was to analyze the effects of allopurinol on the antioxidant defense in the liver of Wistar rats. Twenty male rats were divided into two groups: Control (C) and Allopurinol (ALO). The drug was administered to the animals of the ALO group, while in group C there was a vehicle (saline) administration, both for 3 days. The results indicated a significant reduction in the activity of the antioxidant enzymes in the ALO group compared to the group C. From these results it was suggested that allopurinol was efficient in inhibiting ROS.(AU)

Asunto(s)

Animales , Masculino , Ratas , Ratas Wistar/metabolismo , Hígado , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Alopurinol/administración & dosificación , Alopurinol/uso terapéutico , Antioxidantes

RESUMEN

This study was designed to investigate the effect of pterostilbene (PTS) on cardiac oxidative stress in vitro, as this is a simple and promising methodology to study cardiac disease. Cardiac myoblasts (H9c2 cells) and homogenised cardiac tissue were incubated with the PTS and cyclodextrin (PTS + HPßCD) complex for 1 and 24 h, respectively, at concentrations of 50µM for the cells and 25 and 50µM for cardiac tissue. The PTS + HPßCD complex was used to increase the solubility of PTS in water. After the pretreatment period, cardiomyoblasts were challenged with hydrogen peroxide (6.67µM) for 10 min, while cardiac tissue was submitted to a hydroxyl radical generator system (30 min). Cellular viability, oxidative stress biomarkers (e.g. total reactive oxygen species (ROS), carbonyl assay and lipoperoxidation) and the antioxidant response (e.g. sulfhydryl and the antioxidant enzyme activities of superoxide dismutase, catalase and glutathione peroxidase) were evaluated. In cardiomyoblasts, the PTS + HPßCD complex (50µM) increased cellular viability. Moreover, the PTS + HPßCD complex also significantly increased sulfhydryl levels in the cells submitted to an oxidative challenge. In cardiac tissue, lipid peroxidation, carbonyls and ROS levels were significantly increased in the groups submitted to oxidative damage, while the PTS + HPßCD complex significantly reduced ROS levels in these groups. In addition, the PTS + HPßCD complex also provoked increased catalase activity in both experimental protocols. These data suggest that the PTS + HPßCD complex may play a cardioprotective role through a reduction of ROS levels associated with an improved antioxidant response.

Asunto(s)

Antioxidantes/farmacología , Corazón/efectos de los fármacos , Homeostasis/efectos de los fármacos , Mioblastos Cardíacos/efectos de los fármacos , Estilbenos/farmacología , Animales , Antioxidantes/química , Apoptosis/efectos de los fármacos , Catalasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Ciclodextrinas/química , Glutatión Peroxidasa/metabolismo , Homeostasis/fisiología , Peróxido de Hidrógeno/antagonistas & inhibidores , Peróxido de Hidrógeno/farmacología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Mioblastos Cardíacos/citología , Mioblastos Cardíacos/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Oxidación-Reducción , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Estilbenos/química , Superóxido Dismutasa/metabolismo

RESUMEN

Physical exercise induces inflammatory and oxidative markers production in the skeletal muscle and this process is under the control of both endogenous and exogenous modulators. Recently, molecular hydrogen (H2) has been described as a therapeutic gas able to reduced oxidative stress in a number of conditions. However, nothing is known about its putative role in the inflammatory and oxidative status during a session of acute physical exercise in sedentary rats. Therefore, we tested the hypothesis that H2 attenuates both inflammation and oxidative stress induced by acute physical exercise. Rats ran at 80% of their maximum running velocity on a closed treadmill inhaling either the H2 gas (2% H2, 21% O2, balanced with N2) or the control gas (0% H2, 21% O2, balanced with N2) and were euthanized immediately or 3 h after exercise. We assessed plasma levels of inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6] and oxidative markers [superoxide dismutase (SOD), thiobarbituric acid reactive species (TBARS) and nitrite/nitrate (NOx)]. In addition, we evaluated the phosphorylation status of intracellular signaling proteins [glycogen synthase kinase type 3 (GSK3α/ß) and the cAMP responsive element binding protein (CREB)] that modulate several processes in the skeletal muscle during exercise, including changes in exercise-induced reactive oxygen species (ROS) production. As expected, physical exercise increased virtually all the analyzed parameters. In the running rats, H2 blunted exercise-induced plasma inflammatory cytokines (TNF-α and IL-6) surges. Regarding the oxidative stress markers, H2 caused further increases in exercise-induced SOD activity and attenuated the exercise-induced increases in TBARS 3 h after exercise. Moreover, GSK3α/ß phosphorylation was not affected by exercise or H2 inhalation. Otherwise, exercise caused an increased CREB phosphorylation which was attenuated by H2. These data are consistent with the notion that H2 plays a key role in decreasing exercise-induced inflammation, oxidative stress, and cellular stress.

Asunto(s)

Antiinflamatorios/farmacología , Antioxidantes/farmacología , Hidrógeno/farmacología , Músculo Esquelético/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Administración por Inhalación , Animales , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/sangre , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Glucógeno Sintasa Quinasa 3 beta/sangre , Glucógeno Sintasa Quinasa 3 beta/genética , Interleucina-1beta/antagonistas & inhibidores , Interleucina-1beta/sangre , Interleucina-1beta/genética , Interleucina-6/antagonistas & inhibidores , Interleucina-6/sangre , Interleucina-6/genética , Isoenzimas/sangre , Isoenzimas/genética , Masculino , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatología , Nitratos/antagonistas & inhibidores , Nitratos/sangre , Nitritos/antagonistas & inhibidores , Nitritos/sangre , Condicionamiento Físico Animal/métodos , Esfuerzo Físico/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/sangre , Carrera , Superóxido Dismutasa/sangre , Superóxido Dismutasa/genética , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética

RESUMEN

Mitochondrial dysfunction characterized by impaired bioenergetics, oxidative stress and aldehydic load is a hallmark of heart failure. Recently, different research groups have provided evidence that selective activation of mitochondrial detoxifying systems that counteract excessive accumulation of ROS, RNS and reactive aldehydes is sufficient to stop cardiac degeneration upon chronic stress, such as heart failure. Therefore, pharmacological and non-pharmacological approaches targeting mitochondria detoxification may play a critical role in the prevention or treatment of heart failure. In this review we discuss the most recent findings on the central role of mitochondrial dysfunction, oxidative stress and aldehydic load in heart failure, highlighting the most recent preclinical and clinical studies using mitochondria-targeted molecules and exercise training as effective tools against heart failure.

Asunto(s)

Antioxidantes/uso terapéutico , Materiales Biomiméticos/uso terapéutico , Cardiotónicos/uso terapéutico , Insuficiencia Cardíaca/terapia , Mitocondrias Cardíacas/efectos de los fármacos , Ubiquinona/análogos & derivados , Aldehídos/antagonistas & inhibidores , Aldehídos/metabolismo , Animales , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Metabolismo Energético/efectos de los fármacos , Ejercicio Físico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , Humanos , Malondialdehído/antagonistas & inhibidores , Malondialdehído/metabolismo , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/patología , Estrés Oxidativo/efectos de los fármacos , Especies de Nitrógeno Reactivo/antagonistas & inhibidores , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/química , Ubiquinona/uso terapéutico

RESUMEN

A large number of researches have led to a substantial growth of knowledge about exercise and oxidative stress. Initial investigations reported that physical exercise generates free radical-mediated damages to cells; however, in recent years, studies have shown that regular exercise can upregulate endogenous antioxidants and reduce oxidative damage. Yet, strenuous exercise perturbs the antioxidant system by increasing the reactive oxygen species (ROS) content. These alterations in the cellular environment seem to occur in an exercise type-dependent manner. The source of ROS generation during exercise is debatable, but now it is well established that both contracting and relaxing skeletal muscles generate reactive oxygen species and reactive nitrogen species. In particular, exercises of higher intensity and longer duration can cause oxidative damage to lipids, proteins, and nucleotides in myocytes. In this review, we summarize the ROS effects and interplay of antioxidants in skeletal muscle during physical exercise. Additionally, we discuss how ROS-mediated signaling influences physical exercise in antioxidant system.

Asunto(s)

Antioxidantes/uso terapéutico , Ejercicio Físico , Estilo de Vida Saludable , Músculo Esquelético/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Daño por Reperfusión/prevención & control , Animales , Antiinflamatorios no Esteroideos/metabolismo , Antiinflamatorios no Esteroideos/uso terapéutico , Antioxidantes/metabolismo , Supervivencia Celular , Dieta Saludable , Suplementos Dietéticos , Humanos , Mitocondrias Musculares/enzimología , Mitocondrias Musculares/inmunología , Mitocondrias Musculares/metabolismo , Fatiga Muscular , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/inmunología , Músculo Esquelético/fisiopatología , Mialgia/etiología , Mialgia/prevención & control , Miositis/inmunología , Miositis/prevención & control , Consumo de Oxígeno , Esfuerzo Físico , Especies de Nitrógeno Reactivo/antagonistas & inhibidores , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/inmunología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatología

RESUMEN

BACKGROUND: Oxygen is involved in a variety of physiological reactions in aerobic organisms, such as those produced in the electron transport chain, hydroxylation, and oxygenation. Reactive oxygen species (ROS) are naturally formed as byproducts from these previously reactions involving the O2 molecule; they are made up of superoxide anion (O2-), hydroxyl radical (HO-), hydrogen peroxide (H2O2), nitric oxide (NO), peroxyl (ROO-), and reactive aldehyde (ROCH). Under certain environmental stress conditions, ROS are accumulated causing cellular damage but also triggering the overexpression of several enzyme classes such as superoxide dismutases (SOD), catalases (CAT) and glutathione peroxidases (GPx), which represent an important intrinsic antioxidant defence line. Liver is a key organ in vertebrates including farm animals and human. The oxidative stress plays an important role in systemic malfunctions including hepatic, renal and immunological, disorders. METHODS: This review presents a brief update about the relationship of oxidative stress with hepatic, renal and immunological malfunctions in stressed organisms. Cellular and exogenous hepatoprotective compounds share also the ability to scavenge ROS acting as antioxidants and in many cases as stimulators of immune response in stressed organisms. We present the effect of some hepatoprotectors on the hepatic, renal and immunological function in stressed mice by the jointed evaluation of biological and oxidative stress markers. CONCLUSION: Hepatoprotective effect of several exogenous compounds is very associated with their antioxidant capacity. This fact is relevant for keeping oxidant/antioxidant balance in the respective organs, but also for maintaining the physiological status of the whole organism.

Asunto(s)

Antioxidantes/farmacología , Factores Inmunológicos/farmacología , Hígado/efectos de los fármacos , Sustancias Protectoras/farmacología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Animales , Antioxidantes/química , Factores Inmunológicos/química , Hígado/inmunología , Ratones , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/inmunología , Sustancias Protectoras/química , Especies Reactivas de Oxígeno/inmunología

RESUMEN

Mori folium, the leaf of Morus alba L. (Moraceae), has been traditionally used for various medicinal purposes from ancient times to the present. In this study, we examined the effects of water extract of Mori folium (WEMF) on the production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. Our data indicated that WEMF significantly suppressed the secretion of NO and PGE2 in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects were accompanied by a marked reduction in their regulatory gene expression at the transcription level. WEMF attenuated LPS-induced intracellular ROS production in RAW 264.7 macrophages. It inhibited the nuclear translocation of the nuclear factor-kappa B p65 subunit and the activation of mitogen-activated protein kinases in LPS-treated RAW 264.7 macrophages. Furthermore, WEMF reduced LPS-induced NO production and ROS accumulation in zebrafish. Although more efforts are needed to fully understand the critical role of WEMF in the inhibition of inflammation, the findings of the present study may provide insights into the approaches for Mori folium as a potential therapeutic agent for inflammatory and antioxidant disorders.

Asunto(s)

Mediadores de Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Morus/química , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Pez Cebra , Animales , Expresión Génica , Genes Reguladores , Mediadores de Inflamación/antagonistas & inhibidores , Lipopolisacáridos , Macrófagos/metabolismo , Ratones , Óxido Nítrico/metabolismo , Prostaglandinas E/metabolismo , Células RAW 264.7 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa

RESUMEN

BACKGROUND: Diabetic gastroparesis is a common complication of diabetes mellitus, which mainly affects women. Previous studies have demonstrated that oxidative stress is involved in its onset and development. AIMS: This study evaluated the role of vitamin C on diabetes-associated gastric dysmotility. METHODS: Female rats with streptozotocin-induced diabetes were treated with vehicle (water, 1 mL/kg, p.o.), vitamin C (300 mg/kg/day, p.o.), or insulin (6 IU/day, s.c.). Gastric emptying, in vitro gastric contractility, and biochemistry parameters were analyzed at the end of the treatment (i.e. 8 weeks after the diabetes induction). RESULTS: Vitamin C reversed the delayed gastric emptying of diabetic rats to normal levels, and avoided the changes in the contractile responses to acetylcholine (0.1 nM-1 µM), but not to 5-hydroxytryptamine (0.1 nM-1 µM), in the pylorus and fundus from diabetic rats. Moreover, the contraction evoked by KCl (40 mM) in the fundus, but not in the pylorus, was intensely increased in diabetic rats treated with vitamin C. Notably, the vitamin C reestablished the reduced glutathione levels by 77% and decreased the reactive oxygen species content by 60% in the gastric tissue from diabetic rats. Despite the effects on gastric motility, vitamin C treatment did not change the fasting glycaemia or the glycated hemoglobin of diabetic rats. Unsurprisingly, insulin treatment normalized all parameters evaluated. CONCLUSIONS: Vitamin C exhibited a remarkable beneficial effect on gastric emptying dysfunction in diabetic rats, which was mediated by attenuation of oxidative stress and maintenance of the cholinergic contractile responses in fundus and pylorus.

Asunto(s)

Antioxidantes/uso terapéutico , Ácido Ascórbico/uso terapéutico , Diabetes Mellitus Experimental/tratamiento farmacológico , Vaciamiento Gástrico/efectos de los fármacos , Gastroparesia/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Relación Dosis-Respuesta a Droga , Femenino , Vaciamiento Gástrico/fisiología , Gastroparesia/metabolismo , Gastroparesia/fisiopatología , Estrés Oxidativo/fisiología , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/antagonistas & inhibidores , Especies Reactivas de Oxígeno/metabolismo , Resultado del Tratamiento