RESUMO
In order to understand antidiabetic potential and toxicity, this study aimed to evaluate the acute toxicity and antidiabetic activity of ethanolic extract and ethyl acetate fraction obtained from Coutoubea spicata "nicolau" shoots. Chemical constituents and acute toxicity were investigated. In alloxan-induced diabetic rats, extract and fraction were tested at dose of 100 mg/kg, p.o. Body weight gain, glucose, lipid profile and oxidative stress markers in serum and tissues were determined. In vitro antioxidant activity was performed. Swertiamarin, gentiopicrin, deoxyloganic acid, clovin and robinin, and their p-coumaric ester were identified. Extract and fraction were classified as safe (category 5). In diabetic rats, Coutoubea spicata reduced glycaemia, which was accompanied by body weight recovery gain and attenuation in oxidative stress markers. Fraction showed scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical (ABTS) radicals and reducing power higher than that of the extract. Extract and fraction of Coutoubea spicata didn't present significant toxicity and it can be investigated as a therapeutic alternative in diabetes.
Con el fin de conocer el potencial antidiabético y la toxicidad, este estudio tuvo como objetivo evaluar la toxicidad aguda y la actividad antidiabética del extracto etanólico y la fracción de acetato de etilo obtenidos de los brotes de Coutoubea spicata "Nicolau". Se investigaron los componentes químicos y la toxicidad aguda. En ratas diabéticas inducidas por alloxan, se probaron el extracto y la fracción en dosis de 100 mg/kg, p.o. Se determinó el aumento de peso corporal, la glucosa, el perfil lipídico y los marcadores de estrés oxidativo en suero y tejidos. Se realizó una actividad antioxidante in vitro. Se identificaron la suertiamarina, la gentiopicrina, el ácido desoxilogánico, la clovina y la robinina, así como su éster p-cumárico. El extracto y la fracción se clasificaron como seguros (categoría 5). En ratas diabéticas, Coutoubea spicata redujo la glicemia, lo que se acompañó de una recuperación del peso corporal y de la atenuación de los marcadores de estrés oxidativo. La fracción mostró una actividad de barrido contra los radicales 1,1-difenil-2-picrilhidrazilo (DPPH) y 2,2'-azino-bis (ácido 3-etilbenzotiazolina-6-sulfónico) y un poder reductor superior al del extracto. El extracto y la fracción de Coutoubea spicata no presentaron una toxicidad significativa y pueden ser investigados como alternativa terapéutica en la diabetes.
Assuntos
Extratos Vegetais/toxicidade , Extratos Vegetais/farmacologia , Diabetes Mellitus/tratamento farmacológico , Etanol/química , Extratos Vegetais/química , Fracionamento Químico , Hiperglicemia/tratamento farmacológicoRESUMO
UV radiation can cause damages, such as erythema, skin photoaging, and carcinogenesis. The adoption of protective measures against sun exposure is essential to prevent these damages, and the interest in using natural substances as an alternative for photoprotection is growing. Thus, hesperetin with antioxidant, anti-inflammatory, and anticancer properties is a promising substance to be used with photochemopreventive action and to protect the skin from damage induced by UV radiation. Therefore, the present study aimed to develop a topical formulation based on AAMVPC gel containing hesperetin and evaluate its photoprotective effect on the skin of rats exposed to UVA-UVB radiation. The animals were submitted to the irradiation protocol UVA-UVB, and at the end, erythema, lipid peroxidation, and activity of the antioxidant enzyme catalase and superoxide dismutase were evaluated. Additionally, it evaluated the activity of myeloperoxidase and histological changes. The formulation presented a rheological and spreadability profile suitable for cutaneous application. In vivo results demonstrated that the topical formulation of AAMVPC gel containing hesperetin at a concentration of 10% protected the skin from damage induced by UVA-UVB radiation, with the absence of erythema, lipid lipoperoxidation, and inflammation (low myeloperoxidase activity), and increased catalase and superoxide dismutase activities. The morphology and architecture of the dermo-epidermal tissue of these animals were like those observed under normal conditions (non-irradiated animals). Thus, the results showed that hesperetin was able to protect the animals' skin against UV radiation-induced skin damage and the protection mechanisms may be related to the antioxidant and anti-inflammatory properties of this natural product.
Assuntos
Peroxidase , Raios Ultravioleta , Animais , Anti-Inflamatórios/metabolismo , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Catalase , Hesperidina , Hidrogéis/metabolismo , Estresse Oxidativo , Peroxidase/metabolismo , Peroxidase/farmacologia , Ratos , Pele/metabolismo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Raios Ultravioleta/efeitos adversosRESUMO
The objective of the present study was to evaluate the renal function of rural workers in a city of northeastern Brazil. A cross-sectional study was carried out with 208 workers in Boquim, Sergipe, Brazil. Renal function markers and butyrylcholinesterase (BChE) were evaluated and the glomerular filtration rate (GFR) was determined. The sample consisted mainly of illiterate males with a low usage of personal protective equipment and no training. Approximately 40% had some level of renal failure. Relative risk (1.59) of GFR alteration was higher in workers with more than 5 yr of exposure, mainly to organophosphates. Workers more than 60 yr of age presented a 17.06 greater risk for manifesting acute intoxication. Butyrylcholinesterase reduction was associated with reports of intoxication (relative risk of 11.36). We concluded that exposure to pesticides represented a risk factor for the development of nephrotoxic effects and alteration of renal function, which reinforced the need to implement measures to protect rural workers. Environ Toxicol Chem 2021;40:1132-1138. © 2020 SETAC.
Assuntos
Nefropatias , Doenças Profissionais , Exposição Ocupacional , Praguicidas , Agroquímicos , Brasil , Butirilcolinesterase , Estudos Transversais , Humanos , Nefropatias/induzido quimicamente , Masculino , Doenças Profissionais/induzido quimicamenteRESUMO
Farnesol is a sesquiterpene found in several plants, with multiple pharmacological activities. However, pharmacological actions of farnesol in the treatment of cardiac hypertrophy are not yet reported. This study aimed to investigate the effect and regulatory mechanisms of farnesol against isoproterenol-induced pathological cardiac hypertrophy. Male Wistar rats were treated for 8 days with isoproterenol (4.5 mg/kg; i. p.) and with farnesol (50 µM; i. p.). Hearts were subjected to evaluation of left ventricular developed pressure (LVDP), coronary pressure, electrocardiogram, histopathological analysis, reactive oxygen species (ROS) generation, antioxidant enzyme activity, and pro- and anti-apoptosis protein expression. The results showed that severe impairment of LVDP induced by cardiac hypertrophy was significantly prevented by farnesol treatment. Moreover, farnesol attenuated electrocardiographic changes that are characteristic of cardiac hypertrophy, as well as prevented the increase of fibrosis and migration of inflammatory cells in cardiac tissue. Additionally, farnesol treatment prevented the increase of cardiac ROS generation and restored the activity of endogenous antioxidant enzymes, such as SOD and catalase. It was also evidenced that farnesol decreased the ERK1/2, Bax and Caspase 3 activation, and an increase of AKT and Bcl-2 protein expression, which can be associated with the pathological cardiac remodeling and also with cardioprotection mediated by farnesol, respectively. These results suggest that farnesol is a novel therapeutic agent for amelioration of cardiac hypertrophy in rats.
Assuntos
Cardiomegalia/prevenção & controle , Farneseno Álcool/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Agonistas Adrenérgicos beta , Animais , Antioxidantes/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/induzido quimicamente , Eletrocardiografia/efeitos dos fármacos , Isoproterenol , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Dexamethasone is the most clinically used glucocorticoid with an established role in the treatment of a wide spectrum of inflammatory-related diseases. While the therapeutic actions are well known, dexamethasone treatment causes a number of cardiovascular side effects, which are complex, frequent and, in some cases, clinically unnoticeable. Here, we investigated whether a therapeutic regimen of dexamethasone affects cardiac arrhythmogenesis, focusing on the contribution of Nox-derived reactive oxygen species (ROS). Male Wistar rats were treated with dexamethasone (2 mg/kg, i.p.) for 7 days. Afterward, hemodynamic measurements, autonomic modulation, left ventricular function, cardiac fibrosis, reactive oxygen species (ROS) generation, Nox protein expression, superoxide dismutase (SOD) and catalase activities, and arrhythmias incidence were evaluated. Here, we show that dexamethasone increases blood pressure, associated with enhanced cardiac and vascular sympathetic modulation. Moreover, a marked increase in the cardiac ROS generation was observed, whereas the enhanced SOD activity did not prevent the higher levels of lipid peroxidation in the dexamethasone group. On the other hand, increased cardiac Nox 4 expression and hydrogen peroxide decomposition rate was observed in dexamethasone-treated rats, while Nox 2 remained unchanged. Interestingly, although preserved ventricular contractility and ß-adrenergic responsiveness, we found that dexamethasone-treated rats displayed greater interstitial and perivascular fibrosis than control. Surprisingly, despite the absence of arrhythmias at basal condition, we demonstrated, by in vivo and ex vivo approaches, that dexamethasone-treated rats are more susceptible to develop harmful forms of ventricular arrhythmias when challenged with pharmacological drugs or burst pacing-induced arrhythmias. Notably, concomitant treatment with apocynin, an inhibitor of NADPH oxidase, prevented these ectopic ventricular events. Together, our results reveal that hearts become arrhythmogenic during dexamethasone treatment, uncovering the pivotal role of ROS-generating NADPH oxidases for arrhythmias vulnerability.
Assuntos
Arritmias Cardíacas , NADPH Oxidases , Animais , Arritmias Cardíacas/induzido quimicamente , Dexametasona/toxicidade , Masculino , NADPH Oxidases/genética , Ratos , Ratos Wistar , Espécies Reativas de OxigênioRESUMO
Myocardial infarction (MI) leads to high mortality, and pharmacological or percutaneous primary interventions do not significantly inhibit ischemia/reperfusion injuries, particularly those caused by oxidative stress. Recently, research groups have evaluated several naturally occurring antioxidant compounds for possible use as therapeutic alternatives to traditional treatments. Studies have demonstrated that d-limonene (DL), a monoterpene of citrus fruits, possesses antioxidant and cardiovascular properties. Thus, this work sought to elucidate the mechanisms of protection of DL in an isoproterenol-induced murine MI model. It was observed that DL (10 µmol) attenuated 40% of the ST elevation, reduced the infarct area, prevented histological alterations, abolished completely oxidative stress damage, restored superoxide dismutase activity, and suppressed pro-apoptotic enzymes. In conclusion, the present study demonstrated that DL produces cardioprotective effects from isoproterenol-induced myocardial infarction in Swiss mice through suppression of apoptosis.
Assuntos
Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Limoneno/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Animais , Proteínas Reguladoras de Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Eletrocardiografia/efeitos dos fármacos , Síndrome do QT Longo/prevenção & controle , Masculino , Camundongos , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
Obesity is a metabolic disorder associated with adverse health consequences that has increased worldwide at an epidemic rate. This has encouraged many people to utilize nonprescription herbal supplements for weight loss without knowledge of their safety or efficacy. However, mounting evidence has shown that some herbal supplements used for weight loss are associated with adverse effects. Guarana seed powder is a popular nonprescription dietary herb supplement marketed for weight loss, but no study has demonstrated its efficacy or safety when administered alone. Wistar rats were fed four different diets (low-fat diet and Western diet with or without guarana supplementation) for 18 weeks. Metabolic parameters, gut microbiota changes, and toxicity were then characterized. Guarana seed powder supplementation prevented weight gain, insulin resistance, and adipokine dysregulation induced by Western diet compared with the control diet. Guarana induced brown adipose tissue expansion, mitochondrial biogenesis, uncoupling protein-1 overexpression, AMPK activation, and minor changes in gut microbiota. Molecular docking suggested a direct activation of AMPK by four guarana compounds tested here. We propose that brown adipose tissue activation is one of the action mechanisms involved in guarana supplementation-induced weight loss and that direct AMPK activation may underlie this mechanism. In summary, guarana is an attractive potential therapeutic agent to treat obesity.
Assuntos
Adipocinas/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Resistência à Insulina , Paullinia/química , Animais , Dieta Hiperlipídica/efeitos adversos , Dieta Ocidental , Suplementos Nutricionais , Humanos , Masculino , Simulação de Acoplamento Molecular , Obesidade/metabolismo , Ratos , Ratos Wistar , Aumento de Peso , Redução de Peso/efeitos dos fármacosRESUMO
The receptor for advanced glycation endproducts (RAGE) is a transmembrane, immunoglobulin-like receptor that interacts with a broad repertoire of extracellular ligands. RAGE belongs to a family of cell adhesion molecules and is considered a key receptor in the inflammation axis and a potential contributor to the neurodegeneration. The present study aimed to investigate the content and cell localization of RAGE in the brain of Wistar rats subjected to systemic inflammation induced by a single dose of lipopolysaccharide (LPS, 5 mg/kg, i.p.). Fifteen days after LPS administration, the content of RAGE was analyzed in the prefrontal cortex (PFC), hippocampus (HIPP), cerebellum (CB), and substantia nigra (SN) were investigated. RAGE levels increased in all structures, except HIPP; however, immunohistochemistry analysis demonstrated that the cell site of RAGE expression changed from blood vessel-like structures to neuronal cells in all brain areas. Besides, the highest level of RAGE expression was found in SN. Immunofluorescence analysis in SN confirmed that RAGE expression was mainly co-localized in endothelial cells (RAGE/PECAM-1 co-staining) in untreated animals, while LPS-treated animals had RAGE expression predominantly in dopaminergic neurons (RAGE/TH co-staining). Decreased TH levels, as well as increased pro-inflammatory markers (TNF-α, IL-1ß, Iba-1, GFAP, and phosphorylated ERK1/2) in SN, occurred concomitantly to RAGE stimulation in the same site. These results suggest a role for RAGE in the establishment of a neuroinflammation-neurodegeneration axis that develops as a long-term response to systemic inflammation by LPS.
Assuntos
Encéfalo/metabolismo , Encéfalo/patologia , Células Endoteliais/metabolismo , Inflamação/metabolismo , Neurônios/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Biomarcadores/metabolismo , Neurônios Dopaminérgicos/metabolismo , Inflamação/patologia , Lipopolissacarídeos/farmacologia , Masculino , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Ratos Wistar , Substância Negra/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
OBJECTIVES: The treatment of wounds accounts for a considerable fraction of health expenses as well as serious socioeconomic problems. The use of natural substances stands out as a source of new therapeutic discoveries for the wound healing. Thus, this review compiled scientific findings on the applicability of carvacrol and thymol, or essential oils containing at least one of these compounds, for the treatment of wounds. METHODS: This review was performed at PubMed, SCOPUS, Web of Science databases using keywords as wound healing, thymol/carvacrol and essential oils. Thirteen studies were selected for discussion. KEY FINDINGS: Thymol/carvacrol was able to act in the three phases of wound healing. In the first phase, they showed modulatory effect of the inflammatory cytokines, oxidative stress and antimicrobial power. In the second phase, they promoted re-epithelialization, angiogenesis and development of granulation tissue. Finally, in the third phase, they improve the collagen deposition and modulated the growth of fibroblasts and keratinocytes. CONCLUSIONS: These compounds present a high potential for the development of new therapeutic for wound repair. However, dose, efficacy and safety of these compounds for the treatment of wounds, as well as the mechanisms by which those effects can be observed, are challenges for future studies.
Assuntos
Monoterpenos/farmacologia , Óleos Voláteis/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Cimenos , Citocinas/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Timol/farmacologiaRESUMO
BACKGROUND: Currently viewed as a complementary non-pharmacological intervention for preventing cardiac disorders, long-term aerobic training produces cardioprotection through remote ischemic preconditioning (RIPC) mechanisms. However, RIPC triggered by acute exercise remains poorly understood. Although resistance exercise (RE) has been highly recommended by several public health guidelines, there is no evidence showing that RE mediates RIPC. Hence, we investigated whether RE induces cardiac RIPC through nitric oxide synthase (NOS)-dependent mechanism. METHODS AND RESULTS: Acute RE at 40% of the maximal load augmented systemic nitrite levels, associated with increased cardiac eNOS phosphorylation, without affecting nNOS activity. Using an experimental model of myocardial infarction (MI) through ischemia-reperfusion (IR), RE fully prevented the loss of cardiac contractility and the extent of MI size compared to non-exercised (NE) rats. Moreover, RE mitigated aberrant ST-segment and reduced life-threatening arrhythmias induced by IR. Importantly, inhibition of NOS abolished the RE-mediated cardioprotection. After IR, NE rats showed increased cardiac eNOS activity, associated with reduced dimer/monomer ratio. Supporting the pivotal role of eNOS coupling during MI, non-exercised rats displayed a marked generation of reactive oxygen species (ROS) and oxidative-induced carbonylation of proteins, whereas RE prevented these responses. We validated our data demonstrating a restoration of physiological ROS levels in NEâ¯+â¯IR cardiac sections treated with BH4, a cofactor oxidatively depleted during eNOS uncoupling, while cardiac ROS generation from exercised rats remained unchanged, suggesting no physiological needs of supplemental eNOS cofactors. CONCLUSION: Together, our findings strongly indicate that RE mediates RIPC by limiting eNOS uncoupling and mitigates myocardial IR injury.
Assuntos
Precondicionamento Isquêmico/métodos , Óxido Nítrico Sintase Tipo III/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patologia , Western Blotting , Eletrocardiografia , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Rice bran is obtained from the rice polishing process, and this by-product contains many bioactive compounds. In this study, the composition of phenolic compounds from red and black rice brans was determined by HPLC-DAD-MS. Additionally, the neuroprotective ability of these brans in SH-SY5Y cells insulted with hydrogen peroxide (H2O2) was evaluated. The phenolic constituents of rice bran were separated into hydrophilic and pellet fractions. The major phenolic compound in both samples was ferulic acid. Cyanidin 3-glucoside was the main anthocyanin in black rice bran. The hydrophilic and pellet fractions showed a protective effect (38-94%) on SH-SY5Y cells insulted by H2O2 in DCFH-DA assay. No extract showed cytotoxicity in the SRB assay. These results suggest a neuroprotective effect of red and black rice brans extracts due to their high antioxidant capacity, along with the absence of cytotoxicity. Thus, they may potentially be used as sources of bioactive compounds.
Assuntos
Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Oryza/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Sementes/química , Antocianinas/análise , Antioxidantes , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Cumáricos/análise , Glucosídeos/análise , Humanos , Fenóis/análise , Compostos Fitoquímicos/análise , Extratos Vegetais/químicaRESUMO
α-Terpineol (TP) is present in a wide range of essential oils of the genus Eucalyptus, with recognized potential for a range of biological effects, such as analgesic. Hence, our study aimed to investigate the effect of TP on cancer pain induced by sarcoma 180 in Swiss mice. Our results showed that TP reduced significantly mechanical hyperalgesia and spontaneous and palpation-induced nociception, improved paw use without reducing tumor growth and grip strength. Importantly, no evident biochemical and hematological toxicity was oberved. Furthermore, TP increased the tissue antioxidant capacity due to ferric-reducing antioxidant power (FRAP) and glutathione (GSH). TP also reduced inducible nitric oxide synthase (iNOS) immunocontent in the tumors. Molecular docking estimated that TP binds within the same range of iNOS regions (other iNOS inhibitors), such as N-Nitroarginine methyl ester (L-NAME). These data provide strong evidence that TP may be an interesting candidate for the development of new safe analgesic drugs that are effective for cancer pain control.
Assuntos
Analgésicos/uso terapêutico , Dor do Câncer/tratamento farmacológico , Cicloexenos/uso terapêutico , Monoterpenos/uso terapêutico , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Sarcoma 180 , Analgésicos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Monoterpenos Cicloexânicos , Cicloexenos/farmacologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Monoterpenos/farmacologia , Nociceptividade/efeitos dos fármacos , Ligação ProteicaRESUMO
BACKGROUND: Individuals with chronic diseases have persistent pain as the main symptom, which can often reduce their life quality and functional capacity. The suffering of patients results from the interaction of aversive perception of pain with physical disability, social and family isolation, financial worries and fear of mutilation and death. As an individual and subjective phenomenon that involves many complex aspects, chronic pain should be evaluated and treated in its various components. Several drugs are currently used, but besides the high cost, they have side effects that are harmful to patients. Therefore, there is the need to search for new options for pain relief. Natural products as monoterpenes have been the target of many researchers. OBJECTIVE: This systematic review aimed to briefly summarize the knowledge of the analgesic potential of monoterpenes facing chronic pain. RESULTS: After a search in PubMed, Lilacs, Scopus and Cochrane, 27 articles were selected, which described the analgesic potential of 16 monoterpenes for relief of chronic pain. CONCLUSION: After analyzing the data, it can be suggested that these compounds are strong candidates for the treatment of painful states.
Assuntos
Analgésicos/farmacologia , Dor Crônica/tratamento farmacológico , Monoterpenos/farmacologia , Dor Crônica/fisiopatologia , Dor Crônica/psicologia , Pessoas com Deficiência/psicologia , Desenho de Fármacos , Humanos , Qualidade de VidaRESUMO
Achyrocline satureioides (AS, family Asteraceae) is a plant widely used in traditional medicine for stomach, digestive, and gastrointestinal disorders during pregnancy. Studies regarding the indiscriminate use of plant infusions during pregnancy are limited. Recent reports have shown that chronic flavonoid supplementation induces toxicity in vivo and raises the mortality rates of healthy subjects. Therefore, we investigated whether supplementation of pregnant and lactating Wistar rats with two AS inflorescence extracts, consisting of an aqueous (AQ) extract similar to a tea (47 mg·kg-1·day) and a hydroethanolic (HA) extract (35 mg·kg-1·day-1) with a higher flavonoid content, could induce redox-related side effects. Total reactive antioxidant potential (TRAP), thiobarbituric reactive species (TBARS), and total reduced thiol (SH) content were evaluated. Superoxide dismutase (SOD) and catalase (CAT) activities were additionally quantified. Our data suggest that both AQ and HA of AS inflorescence extracts may induce symptoms of toxicity in concentrations of (47 mg·kg-1·day) and (35 mg·kg-1·day-1), respectively, in mothers regarding the delivery index and further decrease of neonatal survival. Of note, significant tissue-specific changes in maternal (liver, kidney, heart, and hippocampus) and pups (liver and kidney) biochemical oxidative parameters were observed. Our findings provide evidence that may support the need to control supplementation with the AQ of AS inflorescence extracts during gestation due to potential toxicity in vivo, which might be related, at least in part, to changes in tissue-specific redox homeostasis and enzymatic activity.
RESUMO
The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor associated with inflammation in most cell types. RAGE up-regulates the expression of proinflammatory mediators and its own expression via activation of NF-kB. Recent works have proposed a role for RAGE in Parkinson's disease (PD). In this study, we used the multimodal blocker of RAGE FPS-ZM1, which has become available recently, to selectively inhibit RAGE in the substantia nigra (SN) of rats intracranially injected with 6-hydroxydopamine (6-OHDA). FPS-ZM1 (40 µg per rat), injected concomitantly with 6-OHDA (10 µg per rat) into the SN, inhibited the increase in RAGE, activation of ERK1/2, Src and nuclear translocation of NF-kB p65 subunit in the SN. RAGE inhibition blocked glial fibrillary acidic protein and Iba-1 upregulation as well as associated astrocyte and microglia activation. Circulating cytokines in serum and CSF were also decreased by FPS-ZM1 injection. The loss of tyrosine hydroxylase and NeuN-positive neurons was significantly inhibited by RAGE blocking. Finally, FPS-ZM1 attenuated locomotory and exploratory deficits induced by 6-OHDA. Our results demonstrate that RAGE is an essential component in the neuroinflammation and dopaminergic denervation induced by 6-OHDA in the SN. Selective inhibition of RAGE may offer perspectives for therapeutic approaches.
Assuntos
Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Oxidopamina/efeitos adversos , Receptor para Produtos Finais de Glicação Avançada/antagonistas & inibidores , Substância Negra/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/patologia , Mediadores da Inflamação/metabolismo , Masculino , NF-kappa B/metabolismo , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Ratos , Substância Negra/efeitos dos fármacos , Substância Negra/patologia , Quinases da Família src/metabolismoRESUMO
Exercise training intensity is the major variant that influences the relationship between exercise, redox balance, and immune response. Supplement intake is a common practice for oxidative stress prevention; the effects of vitamin A (VA) on exercise training are not yet described, even though this molecule exhibits antioxidant properties. We investigated the role of VA supplementation on redox and immune responses of adult Wistar rats subjected to swimming training. Animals were divided into four groups: sedentary, sedentary + VA, exercise training, and exercise training + VA. Over eight weeks, animals were submitted to intense swimming 5 times/week and a VA daily intake of 450 retinol equivalents/day. VA impaired the total serum antioxidant capacity acquired by exercise, with no change in interleukin-1ß and tumor necrosis factor-α levels. In skeletal muscle, VA caused lipid peroxidation and protein damage without differences in antioxidant enzyme activities; however, Western blot analysis showed that expression of superoxide dismutase-1 was downregulated, and upregulation of superoxide dismutase-2 induced by exercise was blunted by VA. Furthermore, VA supplementation decreased anti-inflammatory interleukin-10 and heat shock protein 70 expression, important factors for positive exercise adaptations and tissue damage prevention. Our data showed that VA supplementation did not confer any antioxidative and/or protective effects, attenuating exercise-acquired benefits in the skeletal muscle.
Assuntos
Suplementos Nutricionais/efeitos adversos , Proteínas de Choque Térmico HSP70/antagonistas & inibidores , Interleucina-10/antagonistas & inibidores , Músculo Esquelético/metabolismo , Miosite/etiologia , Estresse Oxidativo , Vitamina A/efeitos adversos , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Western Blotting , Proteínas de Choque Térmico HSP70/metabolismo , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Interleucina-10/metabolismo , Peroxidação de Lipídeos , Masculino , Músculo Esquelético/enzimologia , Músculo Esquelético/imunologia , Miosite/sangue , Miosite/imunologia , Miosite/metabolismo , Oxirredutases/antagonistas & inibidores , Oxirredutases/química , Oxirredutases/metabolismo , Capacidade de Absorbância de Radicais de Oxigênio , Condicionamento Físico Animal/efeitos adversos , Distribuição Aleatória , Ratos WistarRESUMO
Fruit breeding programs have resulted in bioactive compounds increase and health effects. Thus, this study aimed to evaluate the antioxidant activity and neuroprotective effects of the hydroethanolic extracts from six açaí (Euterpe oleracea) genotypes using ABTS, deoxyribose, and glutathione oxidation assays, as well as, SH-SY5Y cells insulted with H2O2. L22P13 genotype showed the highest total content of anthocyanins, while L06P13 showed a high content of total carotenoids. However, the genotypes showed no difference in the antioxidant activity by ABTS and deoxyribose assays. The hydroethanolic extracts from different genotypes of açaí showed a protective effect (13-62%) on SH-SY5Y cells insulted by H2O2 at a concentration of 50µg/mL by DCFH-DA assay. Except L04P16, no genotypes showed cytotoxicity in the SRB assay. These results indicate that açaí genotypes have antioxidant effect against reactive species generated in SH-SY5Y cells, suggesting a neuroprotective effect of the hydroethanolic extracts from these fruits.
Assuntos
Antioxidantes/farmacologia , Euterpe , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Linhagem Celular Tumoral , Euterpe/química , Frutas , Genótipo , Humanos , Neurônios/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND AND AIMS: Shikimic acid (SA) is present in a wide variety of plants and microorganisms used in traditional and folk medicine and also is an essential starting material for the synthesis of the antiviral drug Oseltamivir (Tamiflu®). Some pharmacological actions observed in SA-enriched products include antioxidant and anti-inflammatory activities. Here, we investigated the anti-inflammatory and antinociceptive actions of isolated SA. METHODS: RAW 264.7 macrophage cells were treated with bacterial LPS (1µg/mL) and the effect of SA on the modulation of cell viability, nitric oxide (NO) production, TNF-α, and IL-1ß content and MAPK (ERK1/2 and p38) activation was evaluated. Besides, the anti-hyperalgesic actions of SA on in vivo model of mechanical hyperalgesia induced by carrageenan (CG), dopamine (DA), TNF-α and prostaglandin (PGE2) were assessed. RESULTS: In RAW 264.7 cells, SA suppressed LPS-induced decrease in cell viability and nitrite accumulation to control values and inhibited up-regulation of TNF-α (65%) and IL-1ß (39%). These effects may be mediated at least in part by inhibition of LPS-induced ERK 1/2 (22%) and p38 (17%) phosphorylation. In mice, SA at 50, 100, and 200mg/kg decreased formalin-induced nociceptive behavior (around 50%) and inhibited the inflammatory nociception induced by TNF-α and PGE2 (50 to 75% each). Moreover, SA (100 and 200mg/kg) significantly attenuated the mechanical hyperalgesia induced by CG and DA (25 to 40% each). CONCLUSIONS: These results indicate that SA presents anti-inflammatory actions with potential for development of drugs to treat pro-inflammatory and painful conditions.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Hiperalgesia/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Ácido Chiquímico/uso terapêutico , Animais , Antivirais/uso terapêutico , Citocinas/metabolismo , Imunidade Celular/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Oseltamivir/uso terapêutico , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Shikimic acid (SA), originally extracted from Illicium verum Hook. fil., is an indispensable starting material for the synthesis of the antiviral drug Oseltamivir (Tamiflu(®)) with very limited number of studies regarding its biological effects in vitro. Therefore, we here evaluated the thermoanalytical profile, redox properties, and in vitro effects of SA on human neuronal-like cells (SH-SY5Y). The thermoanalytical profile of SA was studied by using differential scanning calorimetry (DSC) and thermogravimetry/derivative thermogravimetry (TG/DTG) characterization. Both antioxidant potential and in vitro lipoperoxidation levels were analyzed. Cell viability and intracellular reactive species (RS) production was determined by DCF and SRB assays, respectively. Our results show in vitro antioxidant activity of SA without exerting cytotoxic effects on SH-SY5Y cells at tested concentrations of 10 nM, 10 µM, and 10 mM. In addition, SA protected the cells against H2O2-induced toxicity; effect that could be related, at least in part, with decreased intracellular RS production and its antioxidant potential. The present study shows evidence for neuroprotective actions of SA against oxidative stress-induced toxicity on SH-SY5Y cells, inviting for further investigation about its potential use in the context of oxidative stress-associated neurodegenerative diseases.
Assuntos
Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo , Ácido Chiquímico/farmacologia , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio/toxicidade , Neurônios/efeitos dos fármacos , Neurônios/metabolismoRESUMO
BACKGROUND: The present study was carried out to evaluate antioxidant, antinociceptive and anti-inflammatory activities of essential oil from R. maritima (RMO) in experimental protocols. METHODS: The essential oil from the roots and rhizomes of RMO were obtained by hydrodistillation using a Clevenger apparatus, and analyzed by gas chromatography/mass spectrometry (GC/MS). Here, we evaluated free radical scavenging activities and antioxidant potential of RMO using in vitro assays for scavenging activity against hydroxyl radicals, hydrogen peroxide, superoxide radicals, and nitric oxide. The total reactive antioxidant potential (TRAP) and total antioxidant reactivity (TAR) indexes and in vitro lipoperoxidation were also evaluated. The ability of RMO to prevent lipid peroxidation was measured by quantifying thiobarbituric acid-reactive substances (TBARS). NO radical generated at physiological pH was found to be inhibited by RMO, that showed scavenging effect upon SNP-induced NO production at all concentrations. Antinociceptive and anti-inflammatory properties were evaluated by acetic acid writhing reflex, Formalin-induced nociception and Carrageenan-induced edema test. RESULTS: The majors compounds identified was remirol (43.2%), cyperene (13.8%), iso-evodionol (5.8%), cyperotundone (5.7%), caryophyllene oxide (4.9%), and rotundene (4.6%). At the TRAP assay, RMO concentration of 1 mg.mL(-1) showed anti-oxidant effects and at concentration of 1 and 10 ng.mL(-1) RMO showed pro-oxidant effect. RMO at 1 mg.mL(-1) also showed significant anti-oxidant capacity in TAR measurement. Concentrations of RMO from 1 ng.mL(-1) to 100 µg.mL(-1) enhanced the AAPH-induced lipoperoxidation. RMO reduced deoxyribose oxidative damage, induced by the Fenton reaction induction system, at concentrations from 1 ng.mL(-1) to 100 µg.mL(-1). We observed that RMO caused a significant increase in rate of adrenaline auto-oxidation. On the other hand RMO did not present any scavenging effect in H2O2 formation in vitro. The results of this study revealed that RMO has both peripheral and central analgesic properties. The RMO, all doses, orally (p.o.) administered significantly inhibited (p < 0.05, p < 0.01 and p < 0.001) the acetic acid-induced writhings and two phases of formalin-induced nociception in mice. CONCLUSION: The RMO demonstrated antioxidant and analgesic profile which may be related to the composition of the oil.