RESUMEN
OBJECTIVE: The interaction between nitric oxide (NO) and hydrogen sulfide (H2S) in the airways could have significant implications for the pathogenesis and therapeutic effects of both on lung diseases. In this study we investigated whether the beneficial effects of H2S on asthma could be comparable to that inhibition of inducible NO synthase (iNOS). METHODS: Female BALB/C mice sensitized with ovalbumin (OVA) received either the H2S donor sodium hydrosulfide (NaHS, 14µmol/kg) or the iNOS inhibitor 1400W (1mg/kg), 30min before each OVA challenge during six days. On the first, second and sixth days, the leucocyte infiltration in lung parenchyma and bronchoalveolar lavage was evaluated. The aconitase activity (a sensor of O2 formation) and lipid peroxidation, as well as levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were determined in the lung tissues. RESULTS: OVA-challenge caused a significant and time-dependent increase in the eosinophil number in the airways, which was accompanied by a significant decrease of aconitase activity and GSH/GSSG ratio along with enhanced lipid peroxidation in the lungs. Treatment with NaHS or 1400W significantly attenuated the airways eosinophilia that was paralleled by an increase in aconitase activity and decrease of lipid peroxidation. NaHS or 1400W treatments also reversed the decreased GSH/GSSG ratio seen after OVA-challenge. CONCLUSIONS: The present study shows for the first time that the increased GSH/GSSG ratio caused by either H2S supplementation or iNOS-inhibition is a potential mechanism protecting airways against oxidative stress and inflammatory lung diseases.
Asunto(s)
Asma/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Glutatión/metabolismo , Sulfuro de Hidrógeno/uso terapéutico , Pulmón/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Neumonía/tratamiento farmacológico , Aconitato Hidratasa/metabolismo , Animales , Movimiento Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Femenino , Pulmón/inmunología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Neutrófilos/inmunología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Estrés Oxidativo/efectos de los fármacosRESUMEN
Recent studies show that endogenous hydrogen sulfide (H(2)S) plays an anti-inflammatory role in the pathogenesis of airway inflammation. This study investigated whether exogenous H(2)S may counteract oxidative stress-mediated lung damage in allergic mice. Female BALB/c mice previously sensitized with ovalbumin (OVA) were treated with sodium hydrosulfide (NaHS) 30 min before OVA challenge. Forty eight hours after antigen-challenge, the mice were killed and leukocyte counting as well as nitrite plus nitrate concentrations were determined in the bronchoalveolar lavage fluid, and lung tissue was analysed for nitric oxide synthase (NOS) activity, iNOS expression, superoxide dismutase (SOD), catalase, glutathione reductase (GR) and glutathione peroxidase (GPx) activities, thiobarbituric acid reactive species and 3-nitrotyrosine containing proteins (3-NT). Pre-treatment of OVA-sensitized mice with NaHS resulted in significant reduction of both eosinophil and neutrophil migration to the lungs, and prevented the elevation of iNOS expression and activity observed in the lungs from the untreated allergic mice, although it did not affect 3-NT. NaHS treatment also abolished the increased lipid peroxidation present in the allergic mouse lungs and increased SOD, GPx and GR enzyme activities. These results show, for the first time, that the beneficial in vivo effects of the H(2)S-donor NaHS on allergic airway inflammation involve its inhibitory action on leukocyte recruitment and the prevention of lung damage by increasing endogenous antioxidant defenses. Thus, exogenous administration of H(2)S donors may be beneficial in reducing the deleterius impact of allergic pulmonary disease, and might represent an additional class of pharmacological agents for treatment of chronic pulmonary diseases.
Asunto(s)
Sulfuro de Hidrógeno/farmacología , Hipersensibilidad/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Estrés Oxidativo/efectos de los fármacos , Animales , Catalasa/metabolismo , Femenino , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Hipersensibilidad/enzimología , Hipersensibilidad/inmunología , Leucocitos/efectos de los fármacos , Leucocitos/inmunología , Pulmón/enzimología , Pulmón/inmunología , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico Sintasa/metabolismo , Sulfuros/farmacología , Superóxido Dismutasa/metabolismo , Tiobarbitúricos/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMEN
Os autores descrevem um caso de fibrodisplasia ossificante progressiva, doença hereditária caracterizada por calcificações heterotópicas do tecido conectivo, geralmente induzida por trauma, gerando imobilidade permanente das articulações. Hálux valgo, clinodactilia e polegares curtos são as principais malformações congênitas associadas. Manifesta-se na infância, sendo o diagnóstico clínico-radiológico importante, pois procedimentos invasivos exacerbam a doença. Tratamentos disponíveis são apenas paliativos, tendo a prevenção relevância nesse contexto.
The authors describe a case of fibrodysplasia ossificans progressiva, a hereditary disease characterized by heterotopic ossification of the connective tissues, usually triggered by trauma, resulting in permanent immobility of the joints. Hallux valgus, clinodactyly and short thumbs are the main associated congenital anomalies. Fibrodysplasia ossificans progressiva usually develops during early childhood. Clinical and radiological diagnosis is essential, since invasive procedures exacerbate the disease. Only palliative treatments are available and prevention plays an important role in patients with fibrodysplasia ossificans progressiva.