RESUMEN
Arsenic trioxide (As2O3) is utilized for treating patients suffering from hematological malignancies particularly acute promyelocytic leukemia. Unfortunately, the extensive application of this chemotherapeutic agent has been limited due to its adverse effects such as cardiotoxicity. Ellagic acid, as a phenolic compound, has shown to exert antioxidant, anti-inflammatory, antifibrotic, and antiatherogenic properties. It is also capable of protecting against drug toxicity. In this study, we evaluated whether ellagic acid can protect against As2O3-induced heart injury in rats. Thirty-two male Wistar rats were randomly divided into four treatment groups, that is, control (0.2 mL of normal saline, intraperitoneally (ip)), As2O3 (5 mg/kg, ip), As2O3 plus ellagic acid, and ellagic acid (30 mg/kg, orally) groups. The drugs were administered daily for 10 days and pretreatment with ellagic acid was performed 1 h prior to As2O3 injection. Cardiotoxicity was characterized by electrocardiological, biochemical, and histopathological evaluations. Our results showed that ellagic acid pretreatment significantly ameliorated As2O3-induced increase in glutathione peroxidase activity and malondialdehyde concentration ( p < 0.05 and p < 0.001, respectively) and also diminished QTc prolongation ( p < 0.0001) and cardiac tissue damages. Pretreatment with ellagic acid also lowered the increased troponin I ( p < 0.0001) and creatine kinase isoenzyme MB ( p < 0.01) levels in response to As2O3. In conclusion, results of this study demonstrated that ellagic acid has beneficial cardioprotective effects against As2O3 toxicity. It is suggested that the protective effects were mediated by antioxidant properties of ellagic acid.
Asunto(s)
Antioxidantes/farmacología , Arritmias Cardíacas/prevención & control , Arsenicales , Cardiomiopatías/prevención & control , Ácido Elágico/farmacología , Sistema de Conducción Cardíaco/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Óxidos , Animales , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatología , Trióxido de Arsénico , Cardiomiopatías/inducido químicamente , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Cardiotoxicidad , Forma BB de la Creatina-Quinasa/sangre , Citoprotección , Modelos Animales de Enfermedad , Glutatión Peroxidasa/metabolismo , Sistema de Conducción Cardíaco/metabolismo , Sistema de Conducción Cardíaco/fisiopatología , Masculino , Malondialdehído/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Ratas Wistar , Troponina I/sangreRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease of unknown etiology. Recent investigations have demonstrated that the impaired immune response is a common characteristic feature of IPF. Unfortunately, no definitive and effective drug treatment is available that could improve or at least inhibit the progressive course of this fatal disease. That is why one of the main priorities of pulmonary fibrosis investigations is to identify novel and effective molecular targets for preventive and therapeutic interventions. caffeic acid phenethyl ester (CAPE) is one of the most interesting bioactive compounds extracted from bee propolis. It has been shown that CAPE has an antioxidant activity and modulatory impact on immune system. Accordingly, the aim of the present study was to investigate the regulatory effects of CAPE on the levels of type I collagen (COL-1) and Interferon-gamma (IFN-γ) in bleomycin (BLM)-induced pulmonary fibrosis. Immunohistochemistry procedure was employed to assess the effects of CAPE on lung tissue. In this study, male Sprague-Dawley rats were divided into 5 groups (n=8) included 1: Positive control group: bleomycin (BLM). 2: Negative (saline) control group. 3, 4: Treatment groups of 1 and 2: BLM+CAPE (5 and 10 µmol/kg/day, respectively). (5: Sham group: CAPE (10 µmol/kg/day). BLM application resulted in significant changes in the level of studied parameters as compared to the controls. CAPE could decrease type I collagen concentration, modulate IFN-γ level, increase the animals' body weight and decrease the lung index dose-dependently, compared with model group. In conclusion, CAPE may provide a novel therapeutic target for treating pulmonary fibrosis.
RESUMEN
γ-Secretase is an important contributing enzyme in Alzheimer's disease and is therefore an important therapeutic target. However, the impact of γ-secretase inhibition is not well studied in acute neuroinflammation induced by systemic infection. In this study the influence of γ-secretase on the expression of some proinflammatory markers was assessed in the acute phase as well as the subsiding phase of neuroinflammation. Cerebral γ-secretase cleavage activity was measured by a fluorometric assay after lipopolysaccharide (LPS) intraperitoneal administration. Time profiles of TNF-α and COX-II expression were then determined to detect the time points relevant to the maximal inflammatory responses and the subsequent recovery phase. γ-Secretase activity coincident with TNF-α protein expression returned to its basal level till 8-12 h after systemic challenge with low dose LPS while COX-II over expression lasted for 48-72 h later. Pharmacological inhibition of γ-secretase with local or systemic administration of DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) was performed to indicate the results on the developmental and sinking phases of inflammatory responses in 6 and 72 h post LPS respectively. Our results demonstrate that both local and systemic modulation of γ-secretase hyper-activity with DAPT increase the duration of TNF-α, COX-II, and NFκB induction. We consistently found mild augmented apoptosis in animals treated with DAPT as determined by measuring cleaved caspase-3 expression and by TUNEL assay 72 h following LPS injection. These results suggest that γ-secretase modulation interferes with certain immune regulatory pathways which may restrict some inflammatory transcription factors such as NFκB.
Asunto(s)
Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Encéfalo/enzimología , Inhibidores Enzimáticos/farmacología , Inflamación/enzimología , Animales , Western Blotting , Ciclooxigenasa 2/biosíntesis , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Inflamación/inducido químicamente , Lipopolisacáridos/toxicidad , Masculino , FN-kappa B/biosíntesis , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Many studies have shown that hexavalent chromium (Cr(6+)) compounds cause variety of toxicity, such as carcinogenic effects and pulmonary fibrosis. The aim of this study was to investigate the effect of vitamins C and E on hexavalent chromium-induced lung fibrosis in animal model. Rats weighing 180-210 g were used during the study. The negative control group received a single dose of 0.2 ml intratracheal normal saline. Other groups were given single intratracheal instillation of 50 mg/kg sodium dichromate in saline vehicle and then treated with either vitamin C or E orally. Vit C group treated with 75 mg/kg/day vit C. Vit E group treated with 20 mg/kg/day vit E. Vit C+E group treated with 75 mg/kg/day vit C + 20 mg/kg/day vit E. Three weeks after such treatments animals were killed, lungs were removed for histology and biochemical investigation. Collagen and hydroxyproline content of lung tissue were determined using spectrophotometric methods. Hexavalent chromium caused marked alveolar thickening associated with fibroblasts and myofibroblasts proliferation and collagen production in interstitial tissue leading to pulmonary fibrosis. Administration of vitamins C and E reduced the fibrotic damage in lung tissue. The combination of vit E and C had more pronounced effect. From this study it can be concluded that co-administration of vit C & E may significantly diminish the toxic effects of hexavalent chromium on lung.
Asunto(s)
Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Fibrosis Pulmonar/prevención & control , Vitamina E/farmacología , Administración Oral , Contaminantes Ocupacionales del Aire/toxicidad , Animales , Cromo/toxicidad , Colágeno/efectos de los fármacos , Colágeno/metabolismo , Modelos Animales de Enfermedad , Quimioterapia Combinada , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Masculino , Alveolos Pulmonares/metabolismo , Fibrosis Pulmonar/inducido químicamente , Ratas , Ratas Sprague-DawleyRESUMEN
The aim of this study was to verify the role of Vitamins C and E on the cognitive function of young and aged mice. First and second groups of young animals (aged 3 months) received either Vitamin E (250mg/kg per day) or Vitamin C (300mg/kg per day) for 60 days. Third group was treated with the combination of Vitamin E (250mg/kg per day) and Vitamin C (300mg/kg per day) for 60 days. The control group received only vehicle. The aged animal group (aged 15 months) were treated as the young group. Passive avoidance method was used for the assessment of cognitive function in both young and aged animals. The results indicated a significant improvement in the cognitive function of aged mice while there were no significant changes in young animals.
Asunto(s)
Ácido Ascórbico/farmacología , Cognición/efectos de los fármacos , Vitamina E/farmacología , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Animales , Cognición/fisiología , Masculino , Ratones , Tiempo de Reacción/efectos de los fármacos , Tiempo de Reacción/fisiologíaRESUMEN
Although migraine affects about 15% of population and many studies have been performed to find the mechanism and a successful management, the physiopathology of migraine is still largely unknown. The possibility of an immunoglobulin E (IgE)-mediated allergic mechanism and the role of histamine remain controversial. The aim of the present study was to evaluate serum total IgE and histamine levels in migraine patients and the influence of allergy on them. Seventy patients (18-58 years) with migraine without aura were divided into two groups according to their history of allergy (60% with and 40% without allergy). Serum samples were collected during fasting without allowing any premedication during the two periods of attack and remission. There was a control group containing 45 healthy volunteers. Serum total IgE and histamine levels were measured by enzyme-linked immunosorbent assay and fluorimetric methods, respectively. Mean and standard errors of serum histamine (ng/ml) and total IgE (IU/ml) levels were found in the control group to be 48.16 +/- 2.70 and 38.31 +/- 3.20, in the migraine with allergy group 159.11 +/- 4.60 and 303.30 +/- 42.50 and in the migraine without allergy group 105.01 +/- 8.50 and 79.07 +/- 2.70, respectively. Total IgE levels in migraine with allergy group were found to be significantly (P < 0.0001) above that in the control and another group, suggesting an influence of an IgE-mediated mechanism on migraine. Although the plasma histamine levels, which were significantly elevated (P < 0.0001) in patients with migraine, both during headache and symptom-free periods, when compared with the control group, indicate that there is an increased susceptibility to histamine in allergic conditions, this molecule has also an unrelated role in migraine. The relationship between allergy and migraine can be based, in part, on an IgE-mediated mechanism, and histamine release plays an important role. Thus, the avoidance of allergic conditions in migraine patients may be a simple, helpful way for prophylaxis or their treatment.
Asunto(s)
Histamina/sangre , Inmunoglobulina E/sangre , Trastornos Migrañosos/inmunología , Adolescente , Adulto , Femenino , Humanos , Hipersensibilidad/inmunología , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/sangre , Estadísticas no ParamétricasRESUMEN
Although migraine affects about 15 % of the population, and many studies have been performed to find the mechanism and successful management, the physiopathology of migraine is still largely unknown. The possibility of an IgE-mediated allergic mechanism and the role of histamine remains controversial. The aim of the present study was the evaluation of serum total IgE and histamine levels in migraine patients and the intluence of allergy on them. 70 patients (18-58 years) with migraine without aura were divided in to 2 groups according to their history of allergy (60% with and 40% without allergy). Serum samples were collected during fasting without allowing any premedication in 2 conditions of attack and remission periods. There was a control group containing 45 healthy volunteers. Serum total IgE and histamine levels were measured by ELISA and fluorimetric methods respectively. Mean and standard error of serum histamine (ng/ml) and total IgE (lU/mI) levels were found in control group as 48.16+/-2.70, 38.31+/-3.20 and in migraine with an allergy group as 159.11+/-4.60, 303.30+/-42.50 and in migraine without an allergy group as 105.01 +/-8.50, 79.07+/-2.70 respectively. Total IgE levels in migraine group with allergy were found significantly (P<0.0001) above the control and another group suggesting an influence of an IgE-mediated mechanism on migraine. Plasma histamine levels were significantly elevated (P<0.0001) in patients with migraine both during headache and symptom-free periods compared with control group although it shows that there is an increased susceptibility to histamine in allergic conditions, nonetheless this molecule has also an unrelated role in migraine. The relationship between allergy and migraine can be based in part on IgE-mediated mechanism, with histamine release playing an important role. Thus avoidance of allergic conditions in migraine patients may be a simple helpful way to prophylaxis or their treatment.
RESUMEN
Paraquat is a non-selective herbicide which is widely used in agriculture. It has potential of producing pulmonary fibrosis. In this study the therapeutic effect of different doses of sodium cromolyn on the development of paraquat-induced pulmonary fibrosis was investigated. In order to produce lung fibrosis, rats were given single oral dose of paraquat (40 mg kg(-1)). Two groups of animals were nebulised with 6 or 8 mg day(-1) cromolyn (divided into two doses per day) 5 days prior and 2 weeks after paraquat treatment. Control animals were given equivalent volume of normal saline and treated with cromolyn similar to the test groups. Rats were killed at the end of treatment course and lung tissues were tested histologically and biochemically. Histological examination of paraquat-treated animals showed marked infiltration of inflammatory cells in the alveolar spaces, septal thickening and fibrosis. Lesions were evident in many places of sections. Sodium cromolyn could markedly reduce such damages in lung tissue. Lung weight, hydroxyproline and collagen content of lung tissues were elevated significantly (P < 0.05) in paraquat group compared with control group. In cromolyn-treated groups such factors were near to control value and were significantly lower than paraquat group (P < 0.05). Results of this study indicate that sodium cromolyn can decrease the fibrogenic effect of paraquat on lung. Such effect may be due to the stabilising of mast cells and inhibition of inflammatory mediators by sodium cromolyn.
Asunto(s)
Antiasmáticos/farmacología , Cromolin Sódico/farmacología , Fibrosis Pulmonar/tratamiento farmacológico , Animales , Antiasmáticos/uso terapéutico , Colágeno/metabolismo , Cromolin Sódico/uso terapéutico , Femenino , Hidroxiprolina/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Tamaño de los Órganos/efectos de los fármacos , Paraquat/administración & dosificación , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Ratas , Ratas Sprague-DawleyRESUMEN
In numerous tissues, contractility to certain characteristic agents is associated with cells other than muscle, e.g. actin-containing so-called myofibroblasts. Such cells are present in pulmonary interstitium of several mammalian species but their contractility has only been demonstrated from the proliferation of myofibroblasts in fibrotic lung tissues. This study has been done to evaluate such responses in normal tissues in contrast with fibrotic lungs and it was necessary to take account also of smooth muscle reactivity. Distinctive agonists: mepyramine and sodium tungstate characterised myofibroblast mediated contractility, in contrast with acetylcholine and barium chloride as specific smooth muscle stimulants. Histology and immunohistochemistry were used to evaluate the pharmacological results more precisely.