RESUMEN
Although the Achilles tendon is the largest and strongest tendon in the body, healing of the Achilles tendon is the most common injury, and this process is difficult due to poor tendon circulation; moreover, the underlying mechanism has not been fully elucidated. In our study, we aimed to investigate the effects of pentoxifylline and alpha-tocopherol administered separately or in combination on rats with Achilles tendon injury. Forty-eight male Wistar rats weighing 230 ± 30 g were used in the study. The rats were randomly divided into eight groups of six animals each. Tendons were evaluated histopathologically and biomechanically. According to the statistical analysis, the vascularity density in the pentoxifylline group on day 14 was significantly greater than that in the other groups (p < 0.05). The collagen arrangement in the pentoxifylline and alpha-tocopherol groups on day 14 was found to be firmer and smoother than that in the control group (p < 0.05). The collagen arrangement in the pentoxifylline group on day 28 was greater than that in the other groups (p < 0.05). The biomechanical results were significantly greater in all groups (p < 0.05). Pentoxifylline contributed to tendon healing both through neovascularization in the early period and by improving collagen orientation in the late period, while alpha-tocopherol had a positive effect on collagen orientation in the early period. No beneficial effects were observed when pentoxifylline and alpha-tocopherol were used together. We believe that further research is needed to understand the effects of this combination therapy on tendon healing.
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Tendón Calcáneo , Pentoxifilina , Ratas Wistar , Traumatismos de los Tendones , alfa-Tocoferol , Pentoxifilina/uso terapéutico , Pentoxifilina/farmacología , Animales , Tendón Calcáneo/lesiones , Tendón Calcáneo/efectos de los fármacos , alfa-Tocoferol/uso terapéutico , alfa-Tocoferol/farmacología , Masculino , Ratas , Traumatismos de los Tendones/tratamiento farmacológico , Rotura/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Fenómenos Biomecánicos , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Colágeno/metabolismo , Quimioterapia CombinadaRESUMEN
Substantial advancements have been achieved in the realm of cardiac tissue repair utilizing functional hydrogel materials. Additionally, drug-loaded hydrogels have emerged as a research hotspot for modulating adverse microenvironments and preventing left ventricular remodeling after myocardial infarction (MI), thereby fostering improved reparative outcomes. In this study, diacrylated Pluronic F127 micelles were used as macro-cross-linkers for the hydrogel, and the hydrophobic drug α-tocopherol (α-TOH) was loaded. Through the in situ synthesis of polydopamine (PDA) and the incorporation of conductive components, an injectable and highly compliant antioxidant/conductive composite FPDA hydrogel was constructed. The hydrogel exhibited exceptional stretchability, high toughness, good conductivity, cell affinity, and tissue adhesion. In a rabbit model, the material was surgically implanted onto the myocardial tissue, subsequent to the ligation of the left anterior descending coronary artery. Four weeks postimplantation, there was discernible functional recovery, manifesting as augmented fractional shortening and ejection fraction, alongside reduced infarcted areas. The findings of this investigation underscore the substantial utility of FPDA hydrogels given their proactive capacity to modulate the post-MI infarct microenvironment and thereby enhance the therapeutic outcomes of myocardial infarction.
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Hidrogeles , Infarto del Miocardio , Animales , Conejos , Hidrogeles/uso terapéutico , alfa-Tocoferol/uso terapéutico , Infarto del Miocardio/terapia , Miocardio , Remodelación VentricularRESUMEN
Present research work reports the development of doxorubicin (DOX) loaded α-tocopherol polyethylene glycol 1000 succinate (TPGS)-coated cationic liposomes. The developed formulation was evaluated for its anticancer potential and intracellular uptake against the MDA-MB-231 breast cancer cell line. Moreover, hemocompatibility studies were also done on human blood red blood cells for the determination of blood compatibility. The prepared doxorubicin-loaded TPGS liposomes (DOX-LIPO-TPGS) and doxorubicin-loaded cationic liposomes (DOX-LIPO+-TPGS) reveal vesicle size (177.5 ± 2.5 and 201.7 ± 2.3 nm), polydispersity index (0.189 ± 0.01 and 0.218 ± 0.02), zeta potential (-36.9 ± 0.7 and 42 ± 0.9 mv), and % entrapment efficiency (65.88% ± 3.7% and 74.5% ± 3.9%). Furthermore, in vitro, drug release kinetics of the drug alone and drug from formulation shows sustained release behavior of developed formulation with 99.98% in 12 h and 80.98% release of the drug in 72 h, respectively. In addition, cytotoxicity studies and cellular DOX uptake on the MDA-MB-231 breast cancer cell line depict higher cytotoxic and drug uptake potential with better hemocompatibility of DOX-LIPO+-TPGS with respect to DOX. The data from the study revealed that TPGS plays an important role in enhancing the formulation's quality attributes like stability, drug release, cytotoxicity, and hemocompatibility behavior. This may serve that TPGS-coated cationic liposome as a vital candidate for the treatment of cancer and drug delivery in case of breast cancer.
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Neoplasias de la Mama , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Liposomas , alfa-Tocoferol/farmacología , alfa-Tocoferol/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Doxorrubicina/farmacología , Succinatos/uso terapéutico , Línea Celular , Línea Celular TumoralRESUMEN
Introdução: As doenças cardiovasculares (DCV) são a principal causa de morbimortalidade no mundo. Diante disso, são estudadas estratégias de prevenção e tratamento de eventos cardiovasculares. Dentre elas, a vitamina E destaca-se por suas propriedades antioxidantes e anti-inflamatórias, apoiado por descobertas de que maior ingestão dietética de vitamina E e maiores concentrações de α-tocoferol (α-TOH) sérico estão associados com menor risco de eventos cardiovasculares. Com isso, dados sobre o estado nutricional de vitamina E da população e a sua relação com os fatores de risco cardiovascular são estratégias importantes para subsidiar programas e políticas públicas voltadas a prevenção e tratamento das DCV. Objetivo: Avaliar o estado nutricional de vitamina E e a relação com fatores de risco cardiovascular em adultos e idosos do Estudo Brazuca Natal. Métodos: Trata-se de um estudo de diferentes métodos. 1) A revisão narrativa que investigou na literatura estudos populacionais sobre a relação da vitamina E e as DCV, buscando compreender se a deficiência de vitamina E (DVE) também deve ser considerada um problema de saúde pública. 2) Estudo transversal que se decompõe, a partir das variáveis dependentes, em dois artigos científicos. O primeiro artigo desse estudo buscou avaliar a prevalência de DVE e os fatores de risco cardiovascular que estão associados ao status do α-TOH sérico em adultos e idosos do estudo Brazuca Natal. Análise de regressão linear múltipla foi realizada entre o αTOH sérico (variável dependente) e fatores de risco cardiovascular. O segundo artigo do estudo transversal objetivou avaliar o consumo de vitamina E, e identificar as principais fontes alimentares consumidas do micronutriente pela população avaliada. Para tanto, foram analisadas as condições socioeconômicas e demográficas (sexo, idade, cor/raça, escolaridade, renda per capita e distrito sanitário de moradia) e o consumo alimentar de vitamina E (variável dependente). Resultados: Na revisão narrativa foi observado que a DVE pode ser um problema de saúde pública, por ocorrer uma variação de 0,6% a 55,5% de DVE em todo o mundo, com percentuais mais elevados na Ásia e na Europa, onde se destacam as elevadas taxas de mortalidade por DCV. Estudos populacionais sugerem efeitos protetores da vitamina E nas DCV, porém, estudos de intervenção com suplementação de α-TOH não confirmaram a sua ação cardioprotetora. No artigo 2 do estudo transversal foi observado que 24,8% dos adultos e idosos de Natal apresentavam DVE e 89% apresentaram baixas concentrações de αTOH circulante (abaixo de 30 µmol/L). Verificamos que as pessoas do sexo feminino tinham maiores valores médios de α-TOH sérico. Além disso, o índice de adiposidade visceral elevado e maiores valores do escore de risco global foram associados a maiores concentrações de α-TOH sérico. O artigo 3 demonstrou que 95,7% dos indivíduos apresentavam baixa ingestão de vitamina E, considerando a Estimated Average Requirement (EAR) de 12 mg/dia, com menores valores de ingestão em indivíduos acima de 40 anos, mulheres, naqueles com renda per capita menor que um salário-mínimo e com menor escolaridade. O óleo de soja, polpa de açaí e carne vermelha forneceram o maior teor de vitamina E ingerida. Conclusão: A partir da revisão narrativa, foi demonstrado que a DVE pode ser um problema de saúde pública. O estudo transversal observou uma elevada prevalência de DVE na população estudada, em que o sexo, o índice de adiposidade visceral e o escore de risco global estão associados ao α-TOH sérico. Além disso, foi observado um baixo consumo de vitamina E, principalmente, em indivíduos mais velhos, mulheres e com baixa condição socioeconômica. A maior parte da vitamina E consumida era proveniente do óleo de soja, polpa de açaí e carne vermelha, destacando-se também a vitamina E proveniente de alimentos ultraprocessados, principalmente, na população de menor renda (AU).
Introduction: Cardiovascular diseases (CVD) are the principal cause of morbidity and mortality in the world. Therefore, experts have studied strategies for preventing and treating cardiovascular events. One of this knowledge is vitamin E stands out for its antioxidant and anti-inflammatory properties, supported by findings that higher dietary intake of vitamin E and higher concentrations of serum α-tocopherol (α-TOH) are associated with a lower risk of cardiovascular events. Therefore, data on the nutritional status of vitamin E in the population and its relationship with cardiovascular risk factors are relevant strategies to support programs and public policies aimed at preventing and treating CVD. Objective: To evaluate the nutritional status of vitamin E and its association with cardiovascular risk factors in adults and older adults in the Brazuca Natal Study. Methods: This is a study of different methodological strategies. 1) The narrative review aimed to verify if surveys could demonstrate an association between serum vitamin E and the occurrence of CVD. Moreover, we would like to understand whether vitamin E deficiency (VED) should also be considered a public health problem. 2) Cross-sectional study, divided into two scientific articles. The first article of this study sought to evaluate the prevalence of VED and cardiovascular risk factors that are associated with serum α-TOH status in adults and elderly people from the Brazuca Natal study. We performed a multiple linear regression analysis between serum α-TOH (dependent variable) and cardiovascular risk factors. The second article aimed to evaluate vitamin E intake, and we would like to identify the principal food sources of this micronutrient intake. To this end, we analyzed socioeconomic and demographic conditions (sex, age, color/race, education, per capita income, and health district of residence), and vitamin E intake (dependent variable). Results: In the narrative review, we observed that VED could be a public health problem. The prevalence of VED varies from 0.6% to 55.5% in the world, with higher percentages in Asia and Europe, where the high mortality rates from CVD stand out. Population studies suggest the protective effects of vitamin E on CVD. However, intervention studies with α-TOH supplementation have not confirmed its cardioprotective action. In article 2 of the crosssectional study, we observed that 24.8% of adults and older adults in Natal had VED, and 89% had low concentrations of circulating α-TOH (below 30 µmol/L). Furthermore, high visceral adiposity index and higher global risk score values were associated with higher serum α-TOH concentrations. Article 3 demonstrated that 95.7% of individuals had a low intake of vitamin E, considering the Estimated Average Requirement (EAR) of 12 mg/day, with lower intake values in individuals over 40 years of age, women, those who have a per capita income of less than the minimum wage and with less education. Soybean oil, açaí pulp, and red meat provided the highest content of ingested vitamin E. Conclusion: From the narrative review, it was demonstrated that VED can be a public health problem. The cross-sectional study observed a high prevalence of VED in the studied population, in which sex, visceral adiposity index and global risk score are associated with serum α-TOH. Furthermore, a low consumption of vitamin E was observed, mainly in older individuals, women and those with low socioeconomic status. Most of the vitamin E consumed came from soybean oil, açaí pulp and red meat, with vitamin E also coming from ultra-processed foods, especially in the lowerincome population (AU).
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Vitamina E/uso terapéutico , alfa-Tocoferol/uso terapéutico , Ingestión de Alimentos , Factores de Riesgo de Enfermedad Cardiaca , Deficiencia de Vitamina E/patología , Brasil/epidemiología , Modelos Lineales , Indicadores de Morbimortalidad , Estado Nutricional , Estudios Transversales/métodos , Estudios Poblacionales en Salud PúblicaRESUMEN
Alcoholism affects about 2 billion people worldwide. Withdrawal causes a neuroinflammatory response that increases anxiety. α-tocopherol is the most important antioxidant that has its in vivo action currently known. Therefore, this study aimed to evaluate the effect of α-tocopherol on the neuroinflammatory process in brain regions involved in anxiety and its anxiolytic potential during alcohol withdrawal. For this, male Wistar rats were divided into four groups and submitted to a procedure of forced and chronic self-administration of liquid diet containing 6% and 8% ethanol for 15 days, followed by abrupt interruption of treatment. Animals in the control group received the liquid diet without ethanol. Twenty-four or 48 h after ethanol discontinuation, and 30 min after the last administration of α-tocopherol or saline, animals were evaluated in the elevated plus maze, light/dark box, and open field tests. At the end of the tests, each experimental group underwent brain tissue collection for analysis of cytokine levels. The results showed that: alcohol induces the neuroinflammatory process and anxiety; the stress generated by withdrawal can induce oxidative stress, which alters the production of inflammatory cytokines in the amygdaloid nuclei (AN) and medial hypothalamic nucleus (mHN); α-tocopherol exhibited anxiolytic and anti-inflammatory activity, attenuating the anxious behavior of abstinent animals and reducing neuroinflammation in AN and mHN; and the intensity of the anxiolytic and anti-inflammatory effect of α-tocopherol is dose-dependent. These results identify α-tocopherol as a potential therapeutic target supporting the fight against relapse during alcohol withdrawal.
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Alcoholismo , Ansiolíticos , Síndrome de Abstinencia a Sustancias , Animales , Ratas , Masculino , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Alcoholismo/complicaciones , Etanol , alfa-Tocoferol/farmacología , alfa-Tocoferol/uso terapéutico , Ratas Wistar , Ansiedad/tratamiento farmacológico , DietaRESUMEN
This study aimed to analyze the effects of the quercetin (100 mg/kg), 1% glutamine and 1% α-tocopherol antioxidants in the myocardium of rats with streptozotocin-induced diabetes mellitus. Twenty male rats were subdivided into four groups (n = 5): N (normoglycemic); D (diabetic); NT (normoglycemic treated with antioxidants); and DT (diabetic treated with antioxidants) treated for 60 days. Clinical parameters, oxidative stress markers, inflammatory cytokines, myocardial collagen fibers and immunoexpression of superoxide dismutase 1 (SOD-1), glutathione peroxidase-1 (GPx-1), interleukin-1ß (IL-1-ß), transforming growth factor-beta (TGF-ß), and fibroblast growth factor-2 (FGF-2) were evaluated. Results showed reduced body weight, hyperphagia, polydipsia and hyperglycemic state in groups D and DT. The levels of glutathione (GSH) were higher in NT and DT compared to N (p < 0.01) and D (p < 0.001) groups, respectively. Greater GSH levels were found in DT when compared to N animals (p < 0.001). In DT, there was an increase in IL-10 in relation to N, D and NT (p < 0.05), while GPx-1 expression was similar to N and lower compared to D (p < 0.001). TGF-ß expression in DT was greater than N (p < 0.001) group, whereas FGF-2 in DT was higher than in the other groups (p < 0.001). A significant reduction in collagen fibers (type I) was found in DT compared to D (p < 0.05). The associated administration of quercetin, glutamine and α-tocopherol increased the levels of circulating interleukin-10 (IL-10) and GSH, and reduced the number of type I collagen fibers. Combined use of systemic quercetin, glutamine and alpha-tocopherol attenuates myocardial fibrosis in diabetic rats.
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Diabetes Mellitus Experimental , Quercetina , Animales , Antioxidantes/metabolismo , Colágeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Fibrosis , Glutamina/metabolismo , Glutatión/metabolismo , Interleucina-10/metabolismo , Masculino , Estrés Oxidativo , Quercetina/farmacología , Quercetina/uso terapéutico , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , alfa-Tocoferol/farmacología , alfa-Tocoferol/uso terapéuticoRESUMEN
α-tocopherol showed antioxidant, anti-inflammatory and anti-apoptotic abilities in rat brain tissue, thus alleviating cerebral ischemia-reperfusion injury-induced nerve damage.
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Isquemia Encefálica , Daño por Reperfusión , Animales , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Apoptosis , Isquemia Encefálica/tratamiento farmacológico , Estrés Oxidativo , Ratas , Daño por Reperfusión/tratamiento farmacológico , alfa-Tocoferol/farmacología , alfa-Tocoferol/uso terapéuticoRESUMEN
OBJECTIVE: Evaluate the effect of pentoxifylline and α-tocopherol administration in the prevention or treatment of medication-related jaw osteonecrosis (MRONJ). METHODOLOGY: Sixty Wistar rats were divided into three prevention (C-prev, BP-prev and BP/PT-prev) and three treatment groups (C-treat, BP-treat and BP/PT-treat), n = 10. The animals in the BP-prev, BP/PT-prev, BP-treat and BP/PT-treat groups received zoledronic acid (0.1 mg/kg) for 12 weeks, while the animals in the C-prev and C-treat groups received saline solution. At week 6, all animals underwent tooth extraction. Between week 5 and week 12, the BP/PT-prev group was treated with pentoxifylline (50 mg/kg/day) and α-tocopherol (80 mg/kg/day), with euthanasia at the end of week 12. The BP/PT-treat group received the same drug protocol, but it was performed between week 12 and week 16, with euthanasia at the end of week 16. Afterwards, the presence of osteonecrosis was evaluated by clinical analysis, radiographic and histological. RESULTS: BP/PT-treat group showed a reduction in the histological incidence of osteonecrosis by 50%, decrease the percentage of empty osteocyte gaps and the necrotic area, decrease the presence of bone sequestration and increase the number of osteocytes and alveolar blood flow (p < 0.05). However, BP/PT-prev group showed only a reduction in the necrotic area percentage when compared to BP-prev (p < 0.05). CONCLUSIONS: Pentoxifylline and α-tocopherol administration before tooth extraction was not effective in preventing MRONJ. However, this drug protocol was able to reduce MRONJ manifestation when administrate after discontinuation of bisphosphonate, thus it can be considered as a viable strategy for the treatment of this pathological condition.
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Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Osteonecrosis , Pentoxifilina , Animales , Osteonecrosis de los Maxilares Asociada a Difosfonatos/patología , Osteonecrosis de los Maxilares Asociada a Difosfonatos/prevención & control , Conservadores de la Densidad Ósea/farmacología , Difosfonatos , Osteonecrosis/tratamiento farmacológico , Pentoxifilina/farmacología , Pentoxifilina/uso terapéutico , Ratas , Ratas Wistar , Extracción Dental/métodos , alfa-Tocoferol/farmacología , alfa-Tocoferol/uso terapéuticoRESUMEN
Aims: To address the limitations of IR780 by preparing hydrophilic polymer-IR780 conjugates and to employ these conjugates in the assembly of nanoparticles (NPs) intended for cancer photothermal therapy. Materials & methods: The cyclohexenyl ring of IR780 was conjugated for the first time with thiol-terminated poly(2-ethyl-2-oxazoline) (PEtOx). This novel poly(2-ethyl-2-oxazoline)-IR780 (PEtOx-IR) conjugate was combined with D-α-tocopheryl succinate (TOS), leading to the assembly of mixed NPs (PEtOx-IR/TOS NPs). Results: PEtOx-IR/TOS NPs displayed optimal colloidal stability as well as cytocompatibility in healthy cells at doses within the therapeutic range. In turn, the combination of PEtOx-IR/TOS NPs and near-infrared light reduced heterotypic breast cancer spheroid viability to just 15%. Conclusion: PEtOx-IR/TOS NPs are promising agents for breast cancer photothermal therapy.
Conventional anticancer approaches are often associated with severe side effects. Herein, the authors assembled a novel nanoparticle whose therapeutic effect is triggered by laser light. In in vitro assays, the produced nanomaterial was able to, after interacting with laser light, reduce the viability of classic and advanced cancer models. In these conditions, but in the absence of laser light, no cytotoxicity was observed. In this way, the on-demand effect (triggered by laser light) may contribute to reduced side effects. Moreover, the produced nanoparticle revealed good stability, which is important for its future translation.
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Neoplasias de la Mama , Nanopartículas , Fotoquimioterapia , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Fototerapia , Nanopartículas/uso terapéutico , alfa-Tocoferol/uso terapéutico , Línea Celular TumoralRESUMEN
The term vitamin E describes tocopherols and tocotrienols, whose chemical variations result in different biological activities including antioxidants. Neuroprotective effects of alpha-tocopherol against different toxins are assumed, therefore, it is discussed as a possible protective factor for adverse effects in cancer treatment. In July 2020, a systematic search was conducted searching five databases (Embase, Cochrane, PsychInfo, Cinahl, Medline) to find studies concerning the impact of α-tocopherol application and its potential harm on cancer patients. From 7546 search results, 22 publications referring to 20 studies with 1941 patients were included. Included patients were diagnosed with various cancer types and stages. Outcome variables were overall survival of cancer, symptom management of mucositis and chemotherapy-induced peripheral neuropathy (CIPN). The studies had different methodological qualities (mainly acceptable) and reported heterogeneous results: some reported significant improvement of mucositis and CIPN while others did not find changes concerning these endpoints. Due to heterogeneous results and methodical limitations of the included studies, a clear statement regarding the effectiveness of α-tocopherol as complementary treatment for cancer patients is not possible. Despite findings regarding reduction of oral side effects, usage of α-tocopherol during therapy must be discouraged because of potential negative influence on survival rates.
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Mucositis , Neoplasias , Tocotrienoles , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Humanos , Mucositis/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Isoformas de Proteínas , Tocotrienoles/farmacología , Vitamina E/farmacología , alfa-Tocoferol/uso terapéuticoRESUMEN
INTRODUCTION: The aim of this study was to examine the potential application of a targeted proteomic predictive biomarker comprised predominantly of inflammatory proteins in distinguishing those who responded to a previously conducted clinical trial for Parkinson's disease (PD). METHODS: Plasma samples obtained from a biorepository were assayed from a total of n = 520 DATATOP (Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism) clinical trial participants across treatment arms. Support vector machine analyses were conducted to distinguish responder status on primary (need for Levodopa) and secondary trial endpoints (UPDRS Motor and Total Scores). RESULTS: For the α-tocopherol and deprenyl placebo treatment arm (TOC), the targeted proteomic biomarker was able to distinguish responder status with an accuracy (area under the curve [AUC]) of 91% for the primary endpoint while it was 100% across secondary endpoints. For the deprenyl and α-tocopherol placebo treatment arm (DEP), the AUC was 93% for the primary endpoint and 99-100% for the secondary endpoints. For the combined treatment arm, AUC was 87% for the primary and 94-96% for the secondary endpoints. DISCUSSION: The targeted proteomic predictive biomarker was highly accurate in distinguishing responder status across treatment arms thereby supporting the application of a precision medicine approach to treating PD.
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Enfermedad de Parkinson , Antiparkinsonianos/uso terapéutico , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Medicina de Precisión , Proteómica , Selegilina/uso terapéutico , alfa-Tocoferol/uso terapéuticoRESUMEN
Clinical trials show that insulin administered intranasally is a promising drug to treat neurodegenerative diseases, but at high doses its use may result in cerebral insulin resistance. Identifying compounds which could enhance the protective effects of insulin, may be helpful to reduce its effective dose. Our aim was thus to study the efficiency of combined use of insulin and α-tocopherol (α-T) to increase the viability of cultured cortical neurons under oxidative stress conditions and to normalize the metabolic disturbances caused by free radical reaction activation in brain cortex of rats with two-vessel forebrain ischemia/reperfusion injury. Immunoblotting, flow cytometry, colorimetric, and fluorometric techniques were used. α-T enhanced the protective and antioxidative effects of insulin on neurons in oxidative stress, their effects were additive. At the late stages of oxidative stress, the combined action of insulin and α-T increased Akt-kinase activity, inactivated GSK-3beta and normalized ERK1/2 activity in cortical neurons, it was more effective than either drug action. In the brain cortex, ischemia/reperfusion increased the lipid peroxidation product content and caused Na+,K+-ATPase oxidative inactivation. Co-administration of insulin (intranasally, 0.25 IU/rat) and α-T (orally, 50 mg/kg) led to a more pronounced normalization of the levels of Schiff bases, conjugated dienes and trienes and Na+,K+-ATPase activity than administration of each drug alone. Thus, α-T enhances the protective effects of insulin on cultured cortical neurons in oxidative stress and in the brain cortex of rats with cerebral ischemia/reperfusion injury.
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Isquemia Encefálica/tratamiento farmacológico , Insulina/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , alfa-Tocoferol/uso terapéutico , Animales , Encéfalo/citología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Células Cultivadas , Sinergismo Farmacológico , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Daño por Reperfusión/metabolismoRESUMEN
Arsenic is considered a worldwide pollutant that can be present in drinking water. Arsenic exposure is associated with various diseases, including cancer. Antioxidants as selenite and α-tocopherol-succinate have been shown to modulate arsenic toxic effects. Since changes in STAT3 and PSMD10 gene expression have been associated with carcinogenesis, the aim of this study was to evaluate the effect of arsenic exposure and co-treatments with selenite or α-tocopherol-succinate on the expression of these genes, in the livers of chronically exposed Syrian golden hamsters. Animals were divided into six groups: (i) control, (ii) chronically treated with 100 ppm arsenic, (iii) treated with 6 ppm α-tocopherol-succinate (α-TOS), (iv) treated with 8.5 ppm selenite, (v) treated with arsenic + α-TOS, and (vi) treated with arsenic + selenite. Urine samples and livers were collected after 20 weeks of continuous exposure. The urine samples were analyzed for arsenic species by atomic absorption spectrophotometry, and real-time RT-qPCR analysis was performed for gene expression evaluation. A reduction in STAT3 expression was observed in the selenite-treated group. No differences in PSMD10 expression were found among groups. Histopathological analysis revealed hepatic lymphocytosis in selenite-treated animals. As a conclusion, long-term exposure to arsenic does not significantly alter the expression of STAT3 and PSMD10 oncogenes in the livers of hamsters; however, selenite down-regulates STAT3 expression and provokes lymphocytosis.
Asunto(s)
Antioxidantes/farmacología , Arsénico/efectos adversos , Hígado/efectos de los fármacos , Linfocitosis/inducido químicamente , Factor de Transcripción STAT3/genética , Ácido Selenioso/farmacología , Administración Oral , Animales , Antioxidantes/administración & dosificación , Arsénico/administración & dosificación , Arsénico/orina , Regulación hacia Abajo/efectos de los fármacos , Estimación de Kaplan-Meier , Hígado/patología , Masculino , Mesocricetus , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Factor de Transcripción STAT3/metabolismo , Ácido Selenioso/administración & dosificación , Aumento de Peso/efectos de los fármacos , alfa-Tocoferol/farmacología , alfa-Tocoferol/uso terapéuticoRESUMEN
The study aim was to evaluate the potential anti-inflammatory effects of vitamin E analogs, especially α-tocopherol and δ-tocopherol. We used male C57BL/6JJcl mice, which were divided into four groups: the control (C), high-fat and high-sucrose diet (H), high-fat and high-sucrose diet+α-tocopherol (Ha) and high-fat and high-sucrose diet+δ-tocopherol (Hd) groups. The mice were fed for 16 weeks. To the high-fat and high-sucrose diet, 800 mg/kg of α-tocopherol or δ-tocopherol was added more. The final body weight was significantly higher in the H group than in the C group. On the other hand, the final body weight was drastically lower in the Ha group and Hd group than in the H group. However, the energy intake was not significantly different among all groups. Therefore, we assumed that α-tocopherol and δ-tocopherol have potential anti-obesity effect. Besides, inflammatory cytokine gene expression was significantly higher in the epididymal fat of the H group than in the C group. These results showed that inflammation was induced by epididymal fat of mice fed a high-fat and high-sucrose diet for 16 weeks. Unfortunately, addition of α-tocopherol or δ-tocopherol to the diet did not restrain inflammation of epididymal fat. Investigation of the anti-inflammatory effects of α-tocopherol or δ-tocopherol in co-cultured 3T3-L1 cells and RAW264.7 cells showed that δ-tocopherol inhibited increased gene expression of the inflammatory cytokines, IL-1ß, IL-6, and iNOS. These results suggest that an anti-inflammatory effect in the δ-tocopherol is stronger than that in the α-tocopherol in vitro. We intend to perform an experiment by in vivo sequentially in the future.
Asunto(s)
Adipocitos/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Inflamación/tratamiento farmacológico , Tocoferoles/farmacología , Células 3T3-L1 , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Animales , Antiinflamatorios , Fármacos Antiobesidad , Peso Corporal/efectos de los fármacos , Dieta Alta en Grasa/efectos adversos , Sacarosa en la Dieta/efectos adversos , Expresión Génica/efectos de los fármacos , Inflamación/etiología , Inflamación/genética , Mediadores de Inflamación/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7 , Tocoferoles/uso terapéutico , alfa-Tocoferol/farmacología , alfa-Tocoferol/uso terapéuticoRESUMEN
Current challenge of using cytokines is its poor distribution and systemic side effects. To avoid this issue, we prepared the tumor-targeted and microenvironment-responsive nanocarriers (TRN), which were consisted of α-tocopheryl succinate (α-TOS) loaded mesoporous silica nanoparticles as cores, and surface-modified by thioketal-linkage, electrostatically coated with carboxymethyl chitin, and further anchored glucose-regulated protein 78-binding peptide as shells for encapsulating IL-12. TRN showed a size of 260 nm after encapsulated IL-12 and α-TOS with loading content of 0.0206% and 7.21%, respectively, and exhibited good biocompatibility to 4 T1 cells and macrophages. Moreover, IL-12/α-TOS loaded TRN displayed obvious anti-tumor efficacy on BALB/c nude mice bearing 4 T1 tumors, which was derived from promoted targeting to tumor tissue, endocytosed by macrophages and locally release IL-12 to subsequently repolarize tumor-associated macrophages into tumoricidal M1 phenotype with reduced side effects. The nanosystem exhibited as a promising strategy with functional conversion of macrophages in tumor microenvironment for anti-tumor therapy.
Asunto(s)
Antineoplásicos/uso terapéutico , Polaridad Celular/efectos de los fármacos , Portadores de Fármacos/química , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Macrófagos Asociados a Tumores/efectos de los fármacos , Animales , Línea Celular Tumoral , Quitina/análogos & derivados , Quitina/química , Quitina/toxicidad , Portadores de Fármacos/toxicidad , Inmunoterapia , Interleucina-12/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanopartículas/toxicidad , Células RAW 264.7 , Dióxido de Silicio/química , Dióxido de Silicio/toxicidad , alfa-Tocoferol/uso terapéuticoRESUMEN
BACKGROUND: Açaí (Euterpe oleracea Mart), a Brazilian fruit, is considered a "superfruit" due its energetic properties and bioactive compounds. The açai's anti-inflammatory effects could attenuate the undesirable metabolic and pro-inflammatory side effects triggered by some antipsychotic drugs, such as Olanzapine (OLZ). It is possible to infer that açai supplement could potentially minimize the adverse effects of OLZ. Aim. This study tested the potential in vitro effects of açai hydroalcoholic extract on the inflammatory activation of the RAW 264.7 macrophage line triggered by OLZ antipsychotic drugs. METHODS: An in vitro protocol was performed using commercial RAW 264.7 macrophages, cultured under sterile conditions at 37°C with 5% CO2 saturation. Initially, a pharmacological curve was defined to determine the concentration of Olanzapine to be used. After this, the cells were supplemented with different concentrations of hydroalcoholic extract of açaí, which had been previously chemically characterized. After 24 and 72 hours of treatment, oxidative and inflammatory tests were performed. Therefore, the aim of this study was to verify whether the hydroalcoholic extract of açaí can modulate the oxy-inflammatory response of olanzapine in vitro. RESULTS: From a preliminary analysis, the açai extract at 5 mg/mL presented higher activity against inflammation triggered by OLZ (0.03 µg/mL). At this concentration, açai was able to reduce several oxidative and inflammatory markers triggered by OLZ (0.03 µg/mL) exposure, such as nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory cytokine levels (IL-1b, IL-6, TNF-a, IFN-g) caused by OLZ (0.03 µg/mL). Moreover, açaí reverted the levels of anti-inflammatory cytokine IL-10 that had been dropped by OLZ exposure to their pre-exposure treatments. CONCLUSIONS: The results suggest that açai extract could be useful in attenuating the peripheral inflammatory states triggered by OLZ. Additional pre-clinical and clinical investigations could be useful in testing therapeutic açai extract supplements.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antipsicóticos/efectos adversos , Euterpe/química , Inflamación/prevención & control , Olanzapina/efectos adversos , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Antocianinas/análisis , Antocianinas/farmacología , Antocianinas/uso terapéutico , Antiinflamatorios/análisis , Antiinflamatorios/farmacología , Antioxidantes/análisis , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Citocinas/metabolismo , Suplementos Dietéticos , Frutas/química , Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , alfa-Tocoferol/análisis , alfa-Tocoferol/farmacología , alfa-Tocoferol/uso terapéuticoRESUMEN
BACKGROUND: There is no established effective treatment for patients with t(1;22)(p13;q13) acute megakaryoblastic leukemia (AMKL) and hepatic fibrosis. OBSERVATION: Here we report the outcomes of 2 t(1;22)(p13;q13) AMKL patients with hepatic fibrosis. One patient died from liver failure despite the control of leukemia. The other patient was successfully treated with reduced-intensity chemotherapy and antifibrosis therapy with tretinoin and α-tocopheryl acetate, the hepatic fibrosis resolved and leukemia was in remission for 3 years. CONCLUSIONS: Reduced-intensity chemotherapy plus antifibrosis therapy with tretinoin and α-tocopheryl acetate could be a treatment option for these patients with t(1;22)(p13;q13) AMKL and hepatic fibrosis.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 22/genética , Leucemia Megacarioblástica Aguda/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Translocación Genética , Tretinoina/uso terapéutico , alfa-Tocoferol/uso terapéutico , Antioxidantes/uso terapéutico , Preescolar , Quimioterapia Combinada , Femenino , Humanos , Recién Nacido , Queratolíticos/uso terapéutico , Leucemia Megacarioblástica Aguda/complicaciones , Leucemia Megacarioblástica Aguda/genética , Leucemia Megacarioblástica Aguda/patología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/genética , Cirrosis Hepática/patología , PronósticoRESUMEN
BACKGROUND: Alpha-Tocopherol (alpha -TCP), one major form of vitamin E, has been known as a treatment for airway allergic inflammation. However, the role and mechanism of alpha-TCP in treating allergic rhinitis remains unclear. OBJECTIVE: In this study we examined the inhibitory function of alpha-TCP in a mouse model of allergic rhinitis. METHODS: Allergic phenotype was examined by hematoxylin and eosin staining. Total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were examined by ELISA. mRNA expression was measured by qPCR, protein levels were examined by Western Blot. RESULTS: Histological analysis of the nasal membranes revealed that there was a significant reduction in inflammatory cells appearance in cross-sections in alpha-TCP treatment of Ovalbumin (OVA)-sensitized mice compared to OVA sensitized animals. In addition, eosinophils were significantly reduced in nasal mucosa of alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Lower total IgE, OVA-specific IgE, OVA-specific IgG1 and OVA-specific IgG2a levels were found in alpha-TCP treatment of OVA-sensitized mice compared to the OVA group. Furthermore, we found that the subepithelial distribution of tryptase positive mast cells was reduced in the alpha-TCP treatment of OVA-sensitized mice. More importantly, the PI3K-PKB pathway was suppressed by alpha-TCP in mast cells. CONCLUSIONS: Our results demonstrated that α-TCP-mediated suppression of PI3K-PKB activity in mast cells is a potential mechanism of anti-allergic function of alpha-TCP
No disponible
Asunto(s)
Animales , Femenino , Ratones , Rinitis Alérgica/tratamiento farmacológico , alfa-Tocoferol/uso terapéutico , Antioxidantes/uso terapéutico , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Western Blotting , Ratones Endogámicos BALB C , Inmunohistoquímica , Hematoxilina , FenotipoRESUMEN
This study aimed to evaluate the protective effect of a topical antioxidant and ultraviolet (UV) shielding action formulation containing riboflavin and D-α-tocopherol polyethylene glycol succinate (TPGS) vitamin E against corneal UV-induced damage in vivo rabbit eyes. In vivo experiments were performed using male albino rabbits, which were divided into four groups. The control group (CG) did not receive any UV irradiation; the first group (IG) was irradiated with a UV-B-UV-A lamp for 30 min; the second (G30) and third (G60) groups received UV irradiation for 30 and 60 min, respectively, and were topically treated with one drop of the antioxidant and shielding formulation every 15 min, starting one hour before irradiation, until the end of UV exposure. The cornea of the IG group showed irregular thickening, detachment of residual fragments of the Descemet membrane, stromal fluid swelling with consequent collagen fiber disorganization and disruption, and inflammation. The cornea of the G30 group showed edema, a mild thickening of the Descemet membrane without fibrillar collagen disruption and focal discoloration, or inflammation. In the G60 group, the cornea showed a more severe thickening, a more abundant fluid accumulation underneath the Descemet membrane with focal detachment, and no signs of severe tissue alterations, as were recorded in the IG group. Our results demonstrate that topical application of eye drops containing riboflavin and TPGS vitamin E counteracts UV corneal injury in exposed rabbits.