RESUMEN
The prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased globally during recent decades. Intake of n-3 polyunsaturated fatty acids (PUFAs), mainly eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3), is believed to be beneficial to the development of NAFLD. However, little information is available with regard to the effect of flaxseed oil rich in α-linolenic acid (ALA, C18:3n-3), a plant-derived n-3 PUFA, in improving NAFLD. This study was to gain the effect of flaxseed oil on NAFLD and further investigate the underlying mechanisms. Apolipoprotein-E knockout (apoE-KO) mice were given a normal chow diet, a western-type high-fat and high-cholesterol diet (WTD), or a WTD diet containing 10% flaxseed oil (WTD + FO) for 12 weeks. Our data showed that consumption of flaxseed oil significantly improved WTD-induced NAFLD, as well as ameliorated impaired lipid homeostasis, attenuated oxidative stress, and inhibited inflammation. These data were associated with the modification effects on expression levels of genes involved in de novo fat synthesis (SREBP-1c, ACC), triacylglycerol catabolism (PPARα, CPT1A, and ACOX1), inflammation (NF-κB, IL-6, TNF-α, and MCP-1), and oxidative stress (ROS, MDA, GSH, and SOD).
Asunto(s)
Aceite de Linaza/química , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Animales , Apolipoproteínas E/metabolismo , Dieta , Masculino , Ratones , Enfermedad del Hígado Graso no Alcohólico/patologíaRESUMEN
The targeting of 5-aminosalicylic acid (5-ASA), a first-line therapeutic agent for mild to moderate active ulcerative colitis (UC), to the site of inflammation has remained a challenge and an unmet requirement in the treatment of UC. However, nanoscale carriers for targeted drug delivery are promising for pharmacotherapy, and nanoparticles improve the pharmacokinetics of the loaded therapeutics based on their physical properties. To design and prepare 5ASAloaded silicon dioxide nanoparticles (5ASASiO2 NPs), a microemulsion method was conducted, and their respective therapeutic effects were validated in a mouse model of UC. Cytotoxicity of 5ASASiO2 NPs was detected in vitro using the Cell Counting Kit8 method. The therapeutic effect of 5ASASiO2 NPs was assessed based on their disease activity index (DAI), colon histopathology, myeloperoxidase (MPO) and levels of tumor necrosis factorα (TNFα) and interleukin6 (IL6). SiO2 NPs were successfully prepared, and cytotoxicity of 5ASASiO2 NPs was identified as being similar to 5ASA and SiO2 NPs. DAI and colonic histopathology scores in the normal dosage, high dosage and the 5ASASiO2 NP groups demonstrated a significant improvement when compared with the model group. DAI in the high dosage and 5ASASiO2 NP groups also demonstrated a significant improvement when compared with the normal dosage group. However, MPO, serum IL6 and TNFα levels in normal dosage, high dosage and 5ASASiO2 NPs groups were significantly lower than in the model group, and these indexes in the high dosage group and 5ASASiO2 NP group were significantly lower than that in the normal dosage group. Expression of IL6 and TNFα mRNA in colonic mucosa in the normal dosage, high dosage and 5ASASiO2 NP group was significantly lower than that in the model group. Colonic mucosal IL6 and TNFα mRNA expression in the high dosage and 5ASASiO2 NP groups was significantly lower than that in the normal dosage group (P<0.05). In conclusion, 5ASASiO2 NPs are a selective drug release system that target the inflamed colon, characteristics of UC, and can greatly increase therapeutic efficacy in UC.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Colitis Ulcerosa/patología , Sistemas de Liberación de Medicamentos , Mesalamina/administración & dosificación , Nanopartículas , Dióxido de Silicio , Animales , Antiinflamatorios no Esteroideos/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Mesalamina/química , Ratones , Nanopartículas/química , Nanopartículas/ultraestructura , Peroxidasa/metabolismo , Índice de Severidad de la Enfermedad , Dióxido de Silicio/químicaRESUMEN
Pulmonary fibrosis (PF) can severely disrupt lung function, leading to fatal consequences. Salidroside is a principal active ingredient of Rhodiola rosea and has recently been reported to protect against lung injures. The present study was aimed at exploring its therapeutic effects on PF. Lung fibrotic injuries were induced in SD rats by a single intratracheal instillation of 5 mg/kg bleomycin (BLM). Then, these rats were administrated with 50, 100, or 200 mg/kg salidroside for 28 days. BLM-triggered structure distortion, collagen overproduction, excessive inflammatory infiltration, and pro-inflammatory cytokine release, and oxidative stress damages in lung tissues were attenuated by salidroside in a dose-dependent manner. Furthermore, salidroside was noted to inhibit IκBα phosphorylation and nuclear factor kappa B (NF-κB) p65 nuclear accumulation while activating Nrf2-antioxidant signaling in BLM-treated lungs. Downregulation of E-cadherin and upregulation of vimentin, fibronectin, and α-smooth muscle actin (α-SMA) indicated an epithelial-mesenchymal transition (EMT)-like shift in BLM-treated lungs. These changes were suppressed by salidroside. The expression of TGF-ß1 and the phosphorylation of its downstream targets, Smad-2/-3, were enhanced by BLM, but weakened by salidroside. Additionally, salidroside was capable of reversing the recombinant TGF-ß1-induced EMT-like changes in alveolar epithelial cells in vitro. Our study reveals that salidroside's protective effects against fibrotic lung injuries are correlated to its anti-inflammatory, antioxidative, and antifibrotic properties.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Glucósidos/uso terapéutico , Pulmón/efectos de los fármacos , Fenoles/uso terapéutico , Fibrosis Pulmonar/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Antiinflamatorios/química , Antioxidantes/química , Bleomicina , Línea Celular , Glucósidos/química , Humanos , Pulmón/inmunología , Pulmón/patología , Factor 2 Relacionado con NF-E2/inmunología , FN-kappa B/inmunología , Fenoles/química , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/patología , Ratas Sprague-Dawley , Rhodiola/química , Proteína Smad2/inmunología , Proteína smad3/inmunología , Factor de Crecimiento Transformador beta1/inmunologíaRESUMEN
Idiopathic pulmonary fibrosis is a progressive and lethal form of interstitial lung disease that lacks effective therapies at present. Glycyrrhizic acid (GA), a natural compound extracted from a traditional Chinese herbal medicine Glycyrrhiza glabra, was recently reported to benefit lung injury and liver fibrosis in animal models, yet whether GA has a therapeutic effect on pulmonary fibrosis is unknown. In this study, we investigated the potential therapeutic effect of GA on pulmonary fibrosis in a rat model with bleomycin (BLM)-induced pulmonary fibrosis. The results indicated that GA treatment remarkably ameliorated BLM-induced pulmonary fibrosis and attenuated BLM-induced inflammation, oxidative stress, epithelial-mesenchymal transition, and activation of transforming growth factor-beta signaling pathway in the lungs. Further, we demonstrated that GA treatment inhibited proliferation of 3T6 fibroblast cells, induced cell cycle arrest and promoted apoptosis in vitro, implying that GA-mediated suppression of fibroproliferation may contribute to the anti-fibrotic effect against BLM-induced pulmonary fibrosis. In summary, our study suggests a therapeutic potential of GA in the treatment of pulmonary fibrosis.
RESUMEN
Idiopathic pulmonary fibrosis is a chronic and progressive fibrotic lung disorder with unknown etiology and a high mortality rate. Tanshinone â ¡A (Tan â ¡A) is a lipophilic diterpene extracted from the Chinese herb Salvia miltiorrhiza Bunge with diverse biological functions. The present study was conducted to evaluate the effects of Tan â ¡A on bleomycin (BLM)induced pulmonary fibrosis in rats. Rats received an intraperitoneal injection of Tan â ¡A and normal rats were used as controls. Severe pulmonary edema, inflammation and fibrosis were observed in the BLMtreated rats and the counts of total cells, neutrophils and lymphocytes were significantly increased in the bronchoalveolar lavage fluids of those rats. These pathological changes were markedly attenuated by subsequent treatment with Tan â ¡A. In addition, BLMinduced increased expression of tumor necrosis factorα, interleukin (IL)1ß, IL6, cyclooxygenase2, prostaglandin E2, malondialdehyde, inducible nitric oxide synthase and nitric oxide in rats, which was also suppressed by Tan â ¡A injection. The present findings suggest therapeutic potential of Tan â ¡A for pulmonary fibrosis.
Asunto(s)
Abietanos/farmacología , Antibióticos Antineoplásicos/efectos adversos , Bleomicina/efectos adversos , Medicamentos Herbarios Chinos/farmacología , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológico , Abietanos/administración & dosificación , Animales , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células , Ciclooxigenasa 2/metabolismo , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/administración & dosificación , Inflamación/patología , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , RatasRESUMEN
Aim. To observe the disease activity index (DAI) and the colonic mucosa damage index (CMDI), detect the colonic mucosal expression of PPARγ, NF-κB, and TNF-α in rats with ulcerative colitis (UC), and to investigate the protective role of rosiglitazone in UC. Methods. Sprague-Dawley (SD) rats were divided into three groups: a control group, a rosiglitazone treatment group, and a UC model group. Rats were sacrificed on days 7, 14, 21, or 35 following administration of treatment after enema and DAI, CMDI and colonic expression of PPARγ, NF-κB, and TNF-α were assessed. Results. In the UC model group, DAI, CDMI and the colonic expression of NF-κB and TNF-α increased significantly compared to the control group at all timepoints, but PPARγ decreased significantly. Furthermore, in the rosiglitazone treatment group, DAI and CMDI decreased significantly on the 14-day, 21-day, and 35-day timepoints compared to the UC model group; the colonic expression of NF-κB and TNF-α decreased compared to UC model group at all timepoints, but the PPARγ expression increased significantly. Conclusions. Rosiglitazone can alleviate colonic mucosal inflammation and have the protective role on UC by upregulating PPARγ expression and downregulating NF-κB and TNF-α expression.
RESUMEN
The aim of this study was to determine the disease activity index (DAI) and the colonic mucosa damage index (CMDI), and to detect the colonic mucosal expression levels of matrix metalloproteinase-2 (MMP-2) and tumor necrosis factor-α (TNF-α) in rats with ulcerative colitis (UC). We also aimed to investigate the protective role of Etiasa in UC. Sprague Dawley (SD) rats were randomly divided into three groups: the control, an Etiasa-treated group and a UC model group. Rats were sacrificed on days 14, 21, 35 or 56 following the administration of treatment by enema and the DAI, CMDI and colonic expression levels of MMP-2 and TNF-α were assessed. In the UC model group, the DAI and CDMI scores and the colonic expression levels of MMP-2 and TNF-α increased significantly compared with the control at all timepoints, and were also significantly higher than those in the Etiasa-treated group. In conclusion, the expression levels of MMP-2 and TNF-α increased significantly in rats with UC. Etiasa reduces colonic mucosal damage by downregulating the expression of MMP-2 and TNF-α.
Asunto(s)
Ácidos Aminosalicílicos/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Metaloproteinasa 2 de la Matriz/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ácidos Aminosalicílicos/farmacología , Animales , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Esquema de Medicación , Enema , Inmunohistoquímica , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
AIM: To evaluate the protective role of AE-941, a matrix metalloproteinase (MMP) inhibitor, on ulcerative colitis (UC) in rats. METHODS: Sprague Dawley (SD) rats were randomly divided into three groups: a control group, an AE-941 treatment group, and an UC model group. Rats were sacrificed on days 7, 21, or 56 following administration of treatment by enema and the disease activity index (DAI), colonic mucosa damage index (CMDI) and colonic expression of MMP-2 and MMP-9 were assessed. RESULTS: DAI and CDMI scores in the UC model group increased significantly compared to the control group at all timepoints (P < 0.001), and also increased significantly at the 21- and 56-d timepoints compared to the AE-941-treated group (DAI: 21- and 56-d = 2.09 ± 0.25, 1.52 ± 0.30 vs 1.55 ± 0.28, 0.59 ± 0.19, respectively, P = 0.040 and 0.007, CMDI: 21- and 56-d = 3.03 ± 0.42, 1.60 ± 0.35 vs 2.08 ± 0.46, 0.86 ± 0.37, respectively, P = 0.040 and 0.005). Furthermore, the colonic expression of MMP-2 and MMP-9 in the UC model group increased significantly compared to the control group (P < 0.001), and also increased compared to the AE-941-treated group on the 21- and 56-d timepoints (MMP-2: 21- and 56-d = 0.6048 ± 0.0522, 0.4163 ± 0.0330 vs 0.3983 ± 0.0218, 0.1093 ± 0.0072, respectively, P = 0.010; MMP-9: 21- and 56-d = 0.6873 ± 0.0472, 0.4328 ± 0.0257 vs 0.5179 ± 0.0305, 0.2673 ± 0.0210, respectively, P = 0.010 and 0.040). CONCLUSION: Expression of MMP-2 and MMP-9 increased significantly in rats with UC. AE-941 can reduce colonic mucosal damage by downregulating the expression of MMP-2 and MMP-9.
Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Inhibidores Enzimáticos/farmacología , Metaloproteasas/antagonistas & inhibidores , Extractos de Tejidos/farmacología , Animales , Colitis Ulcerosa/prevención & control , Colon/efectos de los fármacos , Matriz Extracelular/metabolismo , Inmunohistoquímica , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
This Stroke Rehabilitation Apparatus uses the electromyography triggered neuromuscular electrical stimulation as the means of the major therapeutics, and the fastigial nucleus stimulation as the means of the assistant therapeutics. This paper introduces the overall structure of the apparatus, the principle of its component, the EMG processing based on local nonlinear projective filtering algorithm and the alternating treatment modes. The therapeutic apparatus has the features of non-invasiveness, safety, convenience and strong alternating capability.
Asunto(s)
Terapia por Estimulación Eléctrica/instrumentación , Electromiografía/métodos , Trastornos del Movimiento/rehabilitación , Rehabilitación de Accidente Cerebrovascular , Biorretroalimentación Psicológica , Humanos , Trastornos del Movimiento/etiología , Trastornos del Movimiento/fisiopatología , Desempeño Psicomotor/fisiología , Recuperación de la Función , Accidente Cerebrovascular/fisiopatologíaRESUMEN
Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3beta 17beta-diol (4-androsdiol), 19-nor-4-androstene-3beta-17beta-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI.
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Anabolizantes/química , Anabolizantes/farmacología , Esteroides/química , Esteroides/farmacología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Anabolizantes/administración & dosificación , Animales , Peso Corporal/efectos de los fármacos , Cápsulas , Castración , Suplementos Dietéticos , Dimetilpolisiloxanos/química , Genitales Masculinos/efectos de los fármacos , Genitales Masculinos/crecimiento & desarrollo , Cobayas , Humanos , Imagen por Resonancia Magnética , Masculino , Modelos Animales , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/crecimiento & desarrollo , Nandrolona/sangre , Esteroides/administración & dosificación , Testosterona/sangreRESUMEN
To examine the relationship between myocardial storage iron and body iron burden, as assessed by hepatic storage iron measurements, we studied 22 patients with transfusion-dependent thalassemia syndromes, all being treated with subcutaneous deferoxamine, and 6 healthy subjects. Study participants were examined with a Philips 1.5-T Intera scanner using three multiecho spin echo sequences with electrocardiographic triggering and respiratory navigator gating. Myocardial and hepatic storage iron concentrations were determined using a new magnetic resonance method that estimates total tissue iron stores by separately measuring the two principal forms of storage iron, ferritin and hemosiderin. In a subset of 10 patients with beta-thalassemia major, the hepatic storage iron concentration had been monitored repeatedly for 12-14 years by chemical analysis of tissue obtained by liver biopsy and by magnetic susceptometry. In this subset, we examine the relationship between hepatic iron concentration over time and our current magnetic resonance estimates of myocardial iron stores. No significant relationship was found between simultaneous estimates of myocardial and hepatic storage iron concentrations. By contrast, in the subset of 10 patients with beta-thalassemia major, the correlation between the 5-year average of hepatic iron concentration and the current myocardial storage iron was significant (R = .67, P = .03). In these patients, myocardial storage iron concentrations seem to reflect the control of body iron over a period of years. Magnetic resonance methods promise to provide more effective monitoring of iron deposition in vulnerable tissues, including the liver, heart, and endocrine organs, and could contribute to the development of iron-chelating regimens that more effectively prevent iron toxicity.