RESUMO
Omega-3 polyunsaturated fatty acids (PUFAs) may benefit migraine improvement, though prior studies are inconclusive. This study evaluated the effect of eicosapentaenoic acid (EPA) on episodic migraine (EM) prevention. Seventy individuals with EM participated in a 12-week randomized, double-blind, placebo-controlled trial from March 2020 and May 2022. They were randomly assigned to either the EPA (N = 35, 2 g fish oil with 1.8 g of EPA as a stand-alone treatment daily), or the placebo group (N = 35, 2 g soybean oil daily). Migraine frequency and headache severity were assessed using the monthly migraine days, visual analog scale (VAS), Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), and Pittsburgh Sleep Quality Index (PSQI) in comparison to baseline measurements. The EPA group significantly outperformed the placebo in reducing monthly migraine days (-4.4 ± 5.1 days vs. - 0.6 ± 3.5 days, p = 0.001), days using acute headache medication (-1.3 ± 3.0 days vs. 0.1 ± 2.3 days, p = 0.035), improving scores for headache severity (ΔVAS score: -1.3 ± 2.4 vs. 0.0 ± 2.2, p = 0.030), disability (ΔMIDAS score: -13.1 ± 16.2 vs. 2.6 ± 20.2, p = 0.001), anxiety and depression (ΔHADS score: -3.9 ± 9.4 vs. 1.1 ± 9.1, p = 0.025), and quality of life (ΔMSQ score: -11.4 ± 19.0 vs. 3.1 ± 24.6, p = 0.007). Notably, female particularly benefited from EPA, underscoring its potential in migraine management. In conclusion, high-dose EPA has significantly reduced migraine frequency and severity, improved psychological symptoms and quality of life in EM patients, and shown no major adverse events, suggesting its potential as a prophylactic for EM.
Assuntos
Ácido Eicosapentaenoico , Transtornos de Enxaqueca , Feminino , Humanos , Método Duplo-Cego , Ácido Eicosapentaenoico/uso terapêutico , Cefaleia , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Qualidade de Vida , Resultado do Tratamento , MasculinoRESUMO
Hydroxyapatite (HA) is a major component of the inorganic minerals in the hard tissues of humans and has been widely used as a biomedical ceramic material in orthopedic and dentistry applications. Because human bone contains several impurities, including carbonates, chlorides, fluorides, magnesium, and strontium, human bone minerals differ from stoichiometric HA. Additionally, natural bone is composed of nano-sized HA, and the nanoscale particles exhibit a high level of biological activity. In this paper, HA is prepared via the hydrothermal process because its reaction conditions are easy to control and it has been shown to be quite feasible for large-scale production. Therefore, the hydrothermal process is an effective and convenient method for the preparation of HA. Furthermore, eggshell is adopted as a source of calcium, and mulberry leaf extract is selectively added to synthesize HA. The eggshell accounts for 11% of the total weight of a whole egg, and it consists of calcium carbonate, calcium phosphate, magnesium carbonate, and organic matter. Eggshell contains a variety of trace elements, such as magnesium and strontium, making the composition of the synthesized HA similar to that of the human skeleton. These trace elements exert considerable benefits for bone growth. Moreover, the use of eggshell as a raw material can permit the recycling of biowaste and a reduction in process costs. The purpose of this study is to prepare HA powder via the hydrothermal method and to explore the effects of hydrothermal conditions on the structure and properties of the synthesized HA. The room-temperature precipitation method is used for the control group. Furthermore, the results of an immersion test in simulated body fluid confirm that the as-prepared HA exhibits good apatite-forming bioactivity, which is an essential requirement for artificial materials to bond to living bones in the living body and promote bone regeneration. In particular, it is confirmed that the HA synthesized with the addition of the mulberry leaf extract exhibits good in vitro biocompatibility. The morphology, crystallite size, and composition of the carbonated nano-HA obtained herein are similar to those of natural bones. The carbonated nano-HA appears to be an excellent material for bioresorbable bone substitutes or drug delivery. Therefore, the nano-HA powder prepared in this study has great potential in biomedical applications.
Assuntos
Durapatita , Oligoelementos , Animais , Humanos , Durapatita/química , Magnésio/análise , Casca de Ovo/química , Oligoelementos/análise , Pós/análise , Materiais Biocompatíveis/química , Carbonatos/química , Estrôncio , Extratos Vegetais/análiseRESUMO
Previous studies demonstrated that resveratrol (RES) is able to enhance antioxidant, anti-inflammatory and insulin actions in humans. It is unclear whether RES can be used as ergogenic aids to enhance high-intensity cycling exercise performance and attenuate the high-intensity exercise-induced oxidative stress and inflammation. This study investigated the effect of RES supplementation on oxidative stress, inflammation, exercise-induced fatigue, and endurance performance. Eight male athletes participated in this single-blind crossover designed study and randomly instructed to receive four days of either oral RES (480 mg per day, totally 1920mg) or placebo supplementation. The cycling exercise challenge at 80% maximal oxygen consumption with 60 rpm was performed following 4 days of either RES or placebo supplementation. The total cycling performance time was recorded. In addition, blood samples were obtained to analyze the changes in blood glucose, plasma non-esterified fatty acid, serum lactate dehydrogenase, creatine kinase, uric acid, total antioxidant capacity, malondialdehyde, tumor necrosis factor-α, and interleukin-6. The exhausting time of cycling exercise challenge was not significantly increased in RES compared to that in placebo. However, IL-6 response was significantly decreased during exercise challenge in RES trial, and there were no differences in blood biomarkers, fatigue factors, and antioxidative response. Oral RES supplementation can attenuate exercise-induced IL-6 response but not fatigue and oxidative stress, inflammation response. However, we infer that 4-day oral RES supplementation has no ergogenic property on enhancing the high-intensity cycling exercise performance.
Assuntos
Ciclismo/fisiologia , Fadiga/diagnóstico , Interleucina-6/sangue , Substâncias para Melhoria do Desempenho/administração & dosagem , Resveratrol/administração & dosagem , Administração Oral , Adolescente , Atletas , Desempenho Atlético/fisiologia , Estudos Cross-Over , Fadiga/sangue , Fadiga/imunologia , Fadiga/prevenção & controle , Humanos , Inflamação/sangue , Inflamação/imunologia , Inflamação/prevenção & controle , Interleucina-6/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Método Simples-Cego , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: This study was performed to determine the effects of probiotic supplementation on cholesterol-triglyceride ratio, an indirect marker of insulin resistance, protein-bound uremic toxins, biomarkers of inflammation, and microbial translocation in end-stage renal disease patients on hemodialysis. METHODS: Fifty-six patients aged 39-75 years were assigned into two groups to receive either probiotic sachets (n = 28) or a placebo (n = 28) in a randomized double-blinded placebo-controlled clinical trial. The patients in the probiotic group received twice daily sachets that contained a mixture of three viable and freeze-dried strains: Lactococcus lactis subsp. Lactis LL358, Lactobaccillus salivarius LS159, and Lactobaccillus pentosus LPE588 at high dose (100 billion; 1 × 1011 cfu/day) for 6 months. RESULTS: A total of 50 patients were available for final analysis. Probiotic supplementation did not have a significant influence on cholesterol-triglyceride ratio. Probiotic supplementation for 6 months caused a significant decrease in serum levels of indoxyl sulfate. Compared with the placebo, probiotic supplementation did not result in significant changes in hemoglobin levels, blood urea nitrogen, blood glucose, serum p-cresyl sulfate, inflammatory, and microbial translocation markers. No clinically significant changes in body composition were observed between the two groups during the study period. The probiotic supplementation was well tolerated by all subjects with minimal adverse effects during the 6-month-long study. CONCLUSION: Our results suggest that high-dose multistrain lactobaccillus probiotic supplementation over 6 months as a monotherapy did not significantly decrease markers of insulin resistance, cholesterol-triglyceride ratio, and most of the studied markers, with the exception of levels of indoxyl sulfate in patients on HD.
Assuntos
Lactobacillus , Probióticos , Método Duplo-Cego , Humanos , Lactobacillus acidophilus , Diálise Renal , Toxinas UrêmicasRESUMO
Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified ß-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.
Assuntos
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , PPAR gama/metabolismo , Extratos Vegetais/uso terapêutico , Proteínas Quinases/metabolismo , Sirtuína 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Quinases Proteína-Quinases Ativadas por AMP , Administração Oral , Animais , Antrodia/química , Dieta Hiperlipídica/efeitos adversos , Frutose/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Extratos Vegetais/administração & dosagem , Transdução de SinaisRESUMO
Cardiomyocyte apoptosis is the major risk factor for the development of heart failure (HF). The purpose of this study was to evaluate the effects of Gamma-aminobutyric acid (GABA) tea on hypertension-induced cardiac apoptotic pathways in spontaneously hypertensive rats (SHR). In order to reveal the mechanisms, 36 male SHR at eight weeks of age, 200 g were divided into six groups. One group was fed water as a control group. Other rats were administered one of the following treatments: GABA tea at dose 150 and 300 mg/kg/day as low GABA tea (LGT) and high GABA tea (HGT) groups, respectively, pure GABA at dose 150 and 300 mg/kg/day as LG and HG groups, respectively, green tea (GT) as control of LGT and HGT groups. After 12 weeks, cardiac tissues were analyzed by histological analysis, western blotting, and TUNEL assays. GABA tea, GT, and pure GABA decreased hypertension-induced cardiac abnormalities, including abnormal myocardial architecture. In addition, GABA tea, GT, and pure GABA dramatically increased anti-apoptotic protein, Bcl2. Furthermore, GABA tea, GT, and pure GABA also decreased activated-caspase 9 and activated-caspase 3. Additionally, the survival associated protein IGF-I and PI3K/Akt were enhanced in cardiac tissues upon treatment. Our results showed an optimistic anti-apoptotic and pro-survival effects of GABA tea treatment against hypertensive rat hearts.
Assuntos
Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Chá/química , Ácido gama-Aminobutírico/farmacologia , Animais , Caspase 3/metabolismo , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo , Hipertensão/patologia , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Endogâmicos SHR , Receptores de Somatomedina/metabolismo , Chá/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
High-fat diets induce obesity, leading to cardiomyocyte fibrosis and autophagy imbalance. In addition, no previous studies have indicated that probiotics have potential health effects associated with cardiac fibrosis and autophagy in obese rats. This study investigates the effects of probiotics on high-fat (HF) diet-induced obesity and cardiac fibrosis and autophagy in rat hearts. Eight-week-old male Wistar rats were separated randomly into five equally sized experimental groups: Normal diet (control) and high-fat (HF) diet groups and groups fed a high-fat diet supplemented with low (HL), medium (HM) or high (HH) doses of multi-strain probiotic powders. These experiments were designed for an 8-week trial period. The myocardial architecture of the left ventricle was evaluated using Masson's trichrome staining and immunohistochemistry staining. Key probiotics-related pathway molecules were analyzed using western blotting. Abnormal myocardial architecture and enlarged interstitial spaces were observed in HF hearts. These interstitial spaces were significantly decreased in groups provided with multi-strain probiotics compared with HF hearts. Western blot analysis demonstrated that key components of the TGF/MMP2/MMP9 fibrosis pathways and ERK5/uPA/ANP cardiac hypertrophy pathways were significantly suppressed in probiotic groups compared to the HF group. Autophagy balance is very important in cardiomyocytes. In this study, we observed that the beclin-1/LC3B/Atg7 autophagy pathway in HF was increased after probiotic supplementation was significantly decreased. Together, these results suggest that oral administration of probiotics may attenuate cardiomyocyte fibrosis and cardiac hypertrophy and the autophagy-signaling pathway in obese rats.
Assuntos
Cardiomegalia/dietoterapia , Cardiomiopatias/dietoterapia , Traumatismos Cardíacos/dietoterapia , Obesidade/dietoterapia , Probióticos/administração & dosagem , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Cardiomegalia/fisiopatologia , Cardiomiopatias/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Traumatismos Cardíacos/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Obesidade/fisiopatologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacosRESUMO
Topical hydroquinone serves as a skin whitener and is usually available in cosmetics or on prescription based on the hydroquinone concentration. Quantification of hydroquinone content therefore becomes an important issue in topical agents. High-performance liquid chromatography (HPLC) is the commonest method for determining hydroquinone content in topical agents, but this method is time-consuming and uses many solvents that can become an environmental issue. We report a rapid method for quantifying hydroquinone content by chemiluminescent analysis. Hydroquinone induces the production of hydrogen peroxide in the presence of basic compounds. Hydrogen peroxide induced by hydroquinone oxidized light-emitting materials such as lucigenin, resulted in the production of ultra-weak chemiluminescence that was detected by a chemiluminescence analyzer. The intensity of the chemiluminescence was found to be proportional to the hydroquinone concentration. We suggest that the rapid (measurement time, 60 s) and virtually solvent-free (solvent volume, <2 mL) chemiluminescent method described here for quantifying hydroquinone content may be an alternative to HPLC analysis.
Assuntos
Hidroquinonas/análise , Medições Luminescentes , Cromatografia Líquida de Alta Pressão , Peróxido de Hidrogênio/química , Estrutura Molecular , OxirreduçãoRESUMO
Present study examined the effects of conjugated linoleic acid (CLA) supplementation on glycogen resynthesis in exercised human skeletal muscle. Twelve male participants completed a cross-over trial with CLA (3.8 g/day for 8 week) or placebo supplements by separation of 8 weeks. CLA is a mixture of trans-10 cis-12 and cis-9 trans-11 isomers (50:50). On experiment day, all participants performed 60-min cycling exercise at 75% VO2 max, then consumed a carbohydrate meal immediately after exercise and recovered for 3 h. Biopsied muscle samples from vastus lateralis were obtained immediately (0 h) and 3 h following exercise. Simultaneously, blood and gaseous samples were collected for every 30 min during 3-h recovery. Results showed significantly increased muscle glycogen content with CLA after a single bout of exercise (P < 0.05). Muscle glucose transporter type 4 expression was significantly elevated immediately after exercise, and this elevation was continued until 3 h after exercise in CLA trial. However, P-Akt/Akt ratio was not significantly altered, while glucose tolerance was impaired with CLA. Gaseous exchange data showed no beneficial effect of CLA on fat oxidation, instead lower non-esterified fatty acid and glycerol levels were found at 0 h. Our findings conclude that CLA supplementation can enhance the glycogen resynthesis rate in exercised human skeletal muscle.
Assuntos
Suplementos Nutricionais , Exercício Físico/fisiologia , Glicogênio/biossíntese , Ácidos Linoleicos Conjugados/administração & dosagem , Músculo Esquelético/metabolismo , Glicemia/metabolismo , Estudos Cross-Over , Ácidos Graxos não Esterificados/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Homeostase , Humanos , Insulina/sangue , Masculino , Proteínas Serina-Treonina Quinases/metabolismo , Ventilação Pulmonar , Adulto JovemRESUMO
Lactic acid bacteria (LAB) are microorganisms that benefit animals with allergic diseases and intestinal disorders such as inflammatory bowel disease. We propose that LAB can prevent cardiomyocytes inflammation and apoptosis in BALB/c mice using an ovalbumin (OVA)-induced allergy. Thirty-nine male BALB/c mice were divided into five groups: normal control, allergy control and three allergy groups each treated with Kefir I (Kefir I), Kefir II (Kefir II) or GM080 products (GM080). The myocardial architecture and apoptotic molecules in the excised left ventricle from these mice were investigated and post-treatment effects were evaluated. The inflammatory pathway, including toll-like receptor 4 (TLR4), phospholate-Jun-N-terminal kinase (p-JNK), JNK1/2 and tumor necrosis factor- alpha (TNF-α) and the mitochondria-dependent apoptosis phospholate-p38 (p-p38), Bcl-2 associated agonist of cell death (Bad), Bcl-2 associated X (Bax) and activated caspase 3, were found to be significant- ly increased in the hearts of allergy mice. The expression of phospholate-nuclear factor-κB (p-NFκB), TNF-α, p-p38 and Bad protein products were reduced or retarded in the Kefir I- or II-treated allergy group. The GM080-treated allergy group exhibited significantly lower p-JNK, JNK1/2, phospholate- Ikappa B (p-IκB), Bax and Bad protein products than the Kefir I and Kefir II allergy groups. These results indicate that LAB can reduce inflammation and prevent apoptosis of cardiomyocytes in the heart of OVA-induced allergy mice.
Assuntos
Hipersensibilidade/prevenção & controle , Lactobacillus , Miocardite/prevenção & controle , Miocárdio/metabolismo , Probióticos/uso terapêutico , Animais , Apoptose , Caspase 3/metabolismo , Citocromos c/metabolismo , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hipersensibilidade/complicações , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias Cardíacas/metabolismo , Miocardite/induzido quimicamente , Miocardite/metabolismo , Miocardite/patologia , Miocárdio/patologia , Ovalbumina , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
Hypercholesterolemia diets are considered as major sources to cause cardiac hypertrophy. This study intends to evaluate the effects of Li-Fu formula on cardiac hypertrophy induced by hypercholesterolemia diet. Twenty-four male Golden Syrian hamsters were randomly divided into control, cholesterol and Li-Fu formula groups and fed with different experimental diets for 2 months. Histopathological analysis and western blotting were performed to measure the myocardial architecture, and various cardiac hypertrophy-associated molecules in the excised left ventricle from hamsters. The ratios of whole heart weight/body weight (BW) and left ventricle weight/BW were significantly higher in the cholesterol group but significantly lower in the Li-Fu formula group. The protein levels of both atrial natriuretic peptide and brain natriuretic peptide were significantly increased in the cholesterol group but significantly reduced in the Li-Fu formula group. Additionally, significantly increased interleukin-6, STAT3, MEK5, p-ERK5 and non-cardiomyocyte proliferate signal molecules such as p-MEK and p-ERK, were detected in the cholesterol group but significantly reduced in the Li-Fu formula group. Notably, no significant variations of inflammatory signaling molecules, including p-P38 and p-JNK, were detected in all groups. Our experimental results demonstrated the significant reductions of cardiac hypertrophy and related eccentric hypertrophy signaling, non-cardiomyocyte proliferate signaling in the excised left ventricle of hamsters from the Li-Fu formula. We suggested the protective effects of Li-Fu formula on cardiac hypertrophy that may be useful in prevention or treatment of hypertrophy-associated cardiovascular diseases.
RESUMO
BACKGROUND: Very limited information has been published regarding cardiac apoptosis in menopausal women or in those after bilateral oophorectomy. The purpose of this study was to evaluate whether cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways are activated in ovariectomized rats. METHODS: Thirty-two female Wistar rats at 6-7 months of age were randomly divided into sham-operated group (Sham) and bilateral ovariectomized group (OVX). Two months after the operation, the cardiac characteristics, myocardial architecture, and two major apoptotic pathways in the excised left ventricle from rats were measured by histopathological analysis, Western blotting and reverse transcription polymerase chain reaction (RT-PCR), and positive TUNEL assays. RESULTS: The whole heart weight, the left ventricular weight, the ratios of whole heart weight to tibia length, and the ratios of left ventricle to tibia length were significantly increased in OVX relative to Sham. Abnormal myocardial architecture, enlarged interstitial spaces, more minor cardiac fibrosis, and more cardiac TUNEL-positive apoptotic cells were observed in OVX. The key components of Fas-dependent apoptosis (TNF-alpha, Fas ligand, Fas death receptors, Fas-associated death domain (FADD), activated caspase 8, and activated caspase 3) and key components of mitochondria-dependent apoptosis (Bad, Bax, Bax-to-Bcl2 ratio, cytosolic cytochrome c, activated caspase 9, and activated caspase 3) were significantly increased in OVX hearts. CONCLUSIONS: The absence of female ovaries will activate the cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which might provide one of possible mechanism for developing heart failure in post-menopause women.
Assuntos
Apoptose/fisiologia , Menopausa/fisiologia , Mitocôndrias Cardíacas/fisiologia , Miocárdio/citologia , Ovário/fisiologia , Receptor fas/fisiologia , Animais , Peso Corporal , Feminino , Mitocôndrias Cardíacas/metabolismo , Miocárdio/metabolismo , Tamanho do Órgão , Ovariectomia , Distribuição Aleatória , Ratos , Ratos Wistar , Receptor fas/metabolismoRESUMO
It is unknown if short-term and long-term intermittent hypobaric hypoxic challenges both exert pro-apoptotic effects on Fas death receptor-dependent apoptotic pathway in rat hearts. Seventy-two Sprague-Dawley rats were randomly assigned into two groups. First, short-term intermittent hypobaric hypoxia (STIHH)-normobaric normoxia (n = 12), hypobaric hypoxia (380 mmHg, 12% O2, 8 hrs/day) for 1 day (n = 12), and for 4 days (n = 12) and second, long-term intermittent hypobaric hypoxia (LTIHH)-normobaric normoxia (n = 12), hypobaric hypoxia for 1 week (n = 12) and 2 weeks (n = 12). After STIHH or LTIHH challenge, Fas receptor related pathway and histopathological analysis in the excised left ventricle was determined by Western blotting, RT-PCR, Hematoxylin-eosin staining, Masson trichrome staining and TUNEL assay. Fas death receptor and TNFalpha were significantly decreased after STIHH whereas Fas receptor, TNFalpha, FAS-associated death domain (FADD), and caspase 8 were increased after LTIHH. In addition, cardiomyocyte disarray and fibrosis were observed in 1 week LTIHH. Cardiac hypertrophy and more severe disarray, fibrosis and cardiac apoptotic activities were observed in 2 week LTIHH. STIHH exerts anti-apoptotic effects on hearts such as downregulation of TNFalpha and Fas receptor whereas LTIHH exerts pro-apoptotic effects such as upregulation of TNFalpha and Fas-mediated apoptotic pathways and lead to cardiac fibrosis and apoptosis. Our findings imply that short-term versus long-term intermittent hypobaric hypoxia exerted protective versus deleterious effects on hearts.
Assuntos
Apoptose , Hipóxia/patologia , Receptor fas/fisiologia , Animais , Cardiomiopatias/patologia , Proteína Ligante Fas/metabolismo , Proteína de Domínio de Morte Associada a Fas/metabolismo , Fibrose , Coração/fisiologia , Hipóxia/fisiopatologia , Masculino , Miocárdio/patologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
Aristolochic acid (AA) is a component identified in traditional Chinese remedies for the treatment of arthritic pain, coughs and gastrointestinal symptoms. However, previous studies have indicated that AA can induce oxidative stress in renal cells leading to nephropathy. αtocopherol exists in numerous types of food, such as nuts, and belongs to the vitamin E isoform family. It possesses antioxidant activities and has been used previously for clinical applications. Therefore, the aim of the present study was to determine whether αtocopherol could reduce AAinduced oxidative stress and renal cell cytotoxicity, determined by cell survival rate, reactive oxygen species detection and apoptotic features. The results indicated that AA markedly induced H2O2 levels and caspase3 activity in renal tubular epithelial cells. Notably, the presence of αtocopherol inhibited AAinduced H2O2 and caspase3 activity. The present study demonstrated that antioxidant mechanisms of αtocopherol may be involved in the increased survival rates from AAinduced cell injury.
Assuntos
Apoptose/efeitos dos fármacos , Ácidos Aristolóquicos/efeitos adversos , Caspase 3/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Túbulos Renais/citologia , Estresse Oxidativo/efeitos dos fármacos , Vitamina E/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Peróxido de Hidrogênio/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , alfa-Tocoferol/farmacologiaRESUMO
OBJECTIVE: To evaluate the effects of Dioscorea on bilateral ovariectomies-induced cardiac Fasdependent and mitochondria-dependent apoptotic pathways. METHODS: Forty-eight female Wistar rats at 6-7 months of age were equally divided into a sham-operated group, and a bilateral ovariectomized (OVX) group for 2 months, and the rats in the OVX group were further fed with 0, 250 or 750 mL/kg Dioscorea spp. daily in the 2nd month. The excised hearts were measured by positive terminal deoxynucleotidyltransferase UTP nick end labeling (TUNEL) assays, western blotting and reverse transcription-polymerase chain reaction. RESULTS: Dioscorea spp. decreased OVX-induced cardiac TUNEL-positive apoptotic cells; decreased OVX-induced TNF-alpha, Fas ligand, Fas death receptors, Fas-associated death domain, activated caspase-8, and -3 (Fas pathways); decreased OVX-induced Bad, Bax, Bax-to-Bcl2 ratio, activated caspase-9, and -3 (mitochondria pathway). CONCLUSIONS: Dioscorea spp. prevented ovariectomy-induced cardiac Fas-dependent and mitochondriadependent apoptotic pathways in rat models. The fifi ndings may provide possible therapeutic effects of dioscorea for potentially preventing cardiac apoptosis after ovariectomy or post-menopause.
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Through a high-fat diet, obesity leads to cardiomyocyte dysfunction and apoptosis. In addition, there is no evidence that probiotics have potential health effects associated with cardiac apoptosis in obese rats. The present study aimed to explore the effects of probiotics on obesity and cardiac apoptosis in rats fed a high-fat diet (HF). Eightweekold male Wistar rats were separated randomly into five equally sized experimental groups: Normal diet (NC) and high-fat diet (HFC) groups, and high-fat diet supplemented with low (HFL), medium (HFM) or high (HFH) doses of multistrain probiotics groups. The rats were subsequently studied for 8 weeks. Food intake and body weights were recorded following sacrifice, and food utilization rates, body fat and serum cholesterol levels were analysed. The myocardial architecture of the left ventricle was evaluated by hematoxylineosin staining, and key apoptoticrelated pathway molecules were analysed by western blotting. Rat weights and triglyceride levels were decreased with oral administration of high doses of probiotics (HFH) compared to the HFC group. Abnormal myocardial architecture and enlarged interstitial spaces were observed in HFC hearts, but were significantly decreased in groups that were provided multistrain probiotics compared with NC hearts. Western blot analysis demonstrated that key components of the Fas receptor and mitochondrialdependent apoptotic pathways were significantly suppressed in multistrain probiotic treated groups compared to the HF group. Additionally, cardiac insulin, such as the insulinlike growth factor I receptor (IGFIR)dependent survival signalling components, were highly induced in left ventricles from rats administered probiotics. Together, these findings strongly suggest that oral administration of probiotics may attenuate cardiomyocyte apoptosis by activation of the phosphatidylinositol3 kinase/AKT survivalsignalling pathway in obese rats.
Assuntos
Apoptose/efeitos dos fármacos , Gorduras na Dieta/efeitos adversos , Miocárdio/metabolismo , Obesidade/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Probióticos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Gorduras na Dieta/farmacologia , Suplementos Nutricionais , Ingestão de Alimentos/efeitos dos fármacos , Masculino , Miocárdio/patologia , Obesidade/induzido quimicamente , Obesidade/patologia , Ratos , Ratos WistarRESUMO
Retinoic acid (RA), vitamin D and 12-Otetradecanoyl phorbol-13-acetate (TPA) can induce HL-60 cells to differentiate into granulocytes, monocytes and macrophages, respectively. Similar to RA and vitamin D, ascorbic acid also belongs to the vitamin family. Highdose ascorbic acid (>100 µM) induces HL60 cell apoptosis and induces a small fraction of HL60 cells to express the granulocyte marker, CD66b. In addition, ascorbic acid exerts an antioxidative stress function. Oxidative stress is required for HL60 cell differentiation following treatment with TPA, however, the effect of ascorbic acid on HL60 cell differentiation in combination with TPA treatment remains to be fully elucidated. The aim of the present study was to investigate the cellular effects of ascorbic acid treatment on TPA-differentiated HL-60 cells. TPA-differentiated HL-60 cells were used for this investigation, this study and the levels of cellular hydrogen peroxide (H2O2), caspase activity and ERK phosphorylation were determined following combined treatment with TPA and ascorbic acid. The results demonstrated that lowdose ascorbic acid (5 µM) reduced the cellular levels of H2O2 and inhibited the differentiation of HL60 cells into macrophages following treatment with TPA. In addition, the results of the present study further demonstrated that lowdose ascorbic acid inactivates the ERK phosphorylation pathway, which inhibited HL60 cell differentiation following treatment with TPA.
Assuntos
Ácido Ascórbico/farmacologia , Diferenciação Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Peróxido de Hidrogênio/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HL-60 , Humanos , Macrófagos , FosforilaçãoRESUMO
Aristolochic acid (AA) is a component of Chinese medicinal herbs, including asarum and aristolochia and has been used in Traditional Chinese Medicine for a long time. Recent studies found that AA has a cytotoxic effect resulting in nephropathy. These studies indicated that AAinduced cytotoxicity is associated with increases in oxidative stress and caspase3 activation. The present study further demonstrated that AA mainly elevates the H2O2 ratio, leading to increases in oxidative stress. Furthermore, the results indicated that AA induces cell death can via caspasedependent and independent pathways. It is desirable to identify means of inhibiting AAinduced renal damage; therefore, the present study applied an antioxidative nutrient, vitamin C, to test whether it can be employed to reduce AAinduced cell cytotoxicity. The results showed that vitamin C decreased AAinduced H2O2 levels, caspase3 activity and cytotoxicity in renal tubular cells. In conclusion, the present study was the first to demonstrate that AAinduced increases of the H2O2 ratio resulted in renal tubular cell death via caspasedependent and independent pathways, and that vitamin C can decrease AAinduced increases in H2O2 levels and caspase3 activity to attenuate AAinduced cell cytotoxicity.
Assuntos
Apoptose/efeitos dos fármacos , Ácidos Aristolóquicos/toxicidade , Ácido Ascórbico/farmacologia , Túbulos Renais/citologia , Túbulos Renais/efeitos dos fármacos , Estresse Oxidativo , Animais , Aristolochia/química , Asarum/química , Caspase 3/metabolismo , Linhagem Celular , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/toxicidade , Peróxido de Hidrogênio/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/patologia , RatosRESUMO
IGF-IIR plays important roles as a key regulator in myocardial pathological hypertrophy and apoptosis, which subsequently lead to heart failure. Salvia miltiorrhiza Bunge (Danshen) is a traditional Chinese medicinal herb used to treat cardiovascular diseases. Tanshinone IIA is an active compound in Danshen and is structurally similar to 17[Formula: see text]-estradiol (E[Formula: see text]. However, whether tanshinone IIA improves cardiomyocyte survival in pathological hypertrophy through estrogen receptor (ER) regulation remains unclear. This study investigates the role of ER signaling in mediating the protective effects of tanshinone IIA on IGF-IIR-induced myocardial hypertrophy. Leu27IGF-II (IGF-II analog) was shown in this study to specifically activate IGF-IIR expression and ICI 182,780 (ICI), an ER antagonist used to investigate tanshinone IIA estrogenic activity. We demonstrated that tanshinone IIA significantly enhanced Akt phosphorylation through ER activation to inhibit Leu27IGF-II-induced calcineurin expression and subsequent NFATc3 nuclear translocation to suppress myocardial hypertrophy. Tanshinone IIA reduced the cell size and suppressed ANP and BNP, inhibiting antihypertrophic effects induced by Leu27IGF-II. The cardioprotective properties of tanshinone IIA that inhibit Leu27IGF-II-induced cell hypertrophy and promote cell survival were reversed by ICI. Furthermore, ICI significantly reduced phospho-Akt, Ly294002 (PI3K inhibitor), and PI3K siRNA significantly reduced the tanshinone IIA-induced protective effect. The above results suggest that tanshinone IIA inhibited cardiomyocyte hypertrophy, which was mediated through ER, by activating the PI3K/Akt pathway and inhibiting Leu27IGF-II-induced calcineurin and NFATC3. Tanshinone IIA exerted strong estrogenic activity and therefore represented a novel selective ER modulator that inhibits IGF-IIR signaling to block cardiac hypertrophy.
Assuntos
Abietanos/farmacologia , Cardiotônicos , Fator de Crescimento Insulin-Like II/antagonistas & inibidores , Miócitos Cardíacos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Estrogênio/metabolismo , Animais , Calcineurina/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Estradiol/análogos & derivados , Estradiol/metabolismo , Fulvestranto , Hipertrofia/genética , Hipertrofia/prevenção & controle , Fator de Crescimento Insulin-Like II/efeitos adversos , Miócitos Cardíacos/efeitos dos fármacos , Fatores de Transcrição NFATC/metabolismo , Fitoterapia , Ratos , Receptor IGF Tipo 2/metabolismo , Receptor IGF Tipo 2/fisiologia , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/fisiologia , Salvia miltiorrhiza/química , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
GABA tea is a tea product that contains a high level of gamma-aminobutyric acid (GABA). This study investigated the effects of GABA tea on the heart in a diabetic rat model. Male Wistar rats were injected with 55mg/kg streptozotocin (STZ) to induce diabetes for 2weeks and then orally given dosages of 4.55 and 45.5mg/kg/day GABA tea extract for 6weeks. The results revealed that fasting blood glucose levels returned to normal levels in GABA tea-treated diabetic rats, but not in the untreated diabetic rats. Additionally, GABA tea effectively inhibited cardiac fibrosis induced by STZ. Further experiments showed that the STZ-induced protein levels of tumor necrosis factor-alpha (TNF-alpha), Fas, activated caspase-8 and caspase-3 were significantly inhibited by the GABA tea treatment. Therefore, our data suggest that the inhibiting effect of GABA tea on STZ-induced cardiac fibrosis in diabetic rats may be mediated by reducing blood glucose and further attenuating TNF-alpha expression and/or Fas/Fas ligand (FasL)-mediated apoptosis. These findings will provide implications for the potential anti-diabetic properties of GABA tea.