RESUMEN
[This corrects the article DOI: 10.1016/j.chmed.2018.12.002.].
RESUMEN
Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of many respiratory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). To evaluate the treatment responses of procaterol and CD38 inhibitors in an ozone-induced AHR mice model, we hypothesized that procaterol and two synthetic CD38 inhibitors (Compounds T and H) might have therapeutic effects on the ozone-induced AHR mice model, and the nuclear factor-kappaB (NF-κB) pathway and the CD38 enzymatic activity might be involved in the mechanisms. With the exception of the Control group, ozone exposure was used to establish an AHR model. Male Kunming mice in the Procaterol and CD38 inhibitors groups were treated with an emulsifier of procaterol hydrochloride, Compound T or H. Results indicated that (1) no drug showed severe toxicity in this study; (2) ozone exposure induced airway inflammation and AHR; (3) intragastric treatment with procaterol and Compound T achieved potent therapeutic effects, but Compound H did not show any therapeutic effect; (4) the NF-κB pathway was involved in both the pathogenic mechanisms of ozone and therapeutic mechanisms of procaterol and Compound T; (5) however, the in vivo effect of Compound T was not caused by its inhibitory activity on CD38. Taken together, procaterol and Compound T are potentially good drugs to treat asthma and COPD complicated with ozone exposure.
Asunto(s)
Antiasmáticos/uso terapéutico , Benzoatos/uso terapéutico , Hiperreactividad Bronquial/tratamiento farmacológico , Indoles/uso terapéutico , Procaterol/uso terapéutico , ADP-Ribosil Ciclasa 1/antagonistas & inhibidores , Animales , Antiasmáticos/farmacología , Benzoatos/farmacología , Hiperreactividad Bronquial/inducido químicamente , Hiperreactividad Bronquial/patología , Hiperreactividad Bronquial/fisiopatología , Pruebas de Provocación Bronquial , Líquido del Lavado Bronquioalveolar/citología , Modelos Animales de Enfermedad , Indoles/farmacología , Recuento de Leucocitos , Pulmón/inmunología , Pulmón/patología , Masculino , Glicoproteínas de Membrana/antagonistas & inhibidores , Cloruro de Metacolina , Ratones , FN-kappa B/inmunología , Ozono , Procaterol/farmacologíaRESUMEN
Parkinson disease (PD) is the second most common neurodegenerative disease, and it cannot be completely cured by current medications. In this study, DJ-1 protein was administrated into medial forebrain bundle of PD model rats those had been microinjected with 6-hydroxydopamine (6-OHDA) or MG-132. We found that DJ-1 protein could reduce apomorphine-induced rotations, inhibit reduction of dopamine contents and tyrosine hydroxylase levels in the striatum, and decrease dopaminergic neuron death in the substantia nigra. In 6-OHDA lesioned rats, uncoupling protein-4, uncoupling protein-5 and superoxide dismutase-2 (SOD2) mRNA and SOD2 protein were increased when DJ-1 protein was co-injected. Simultaneously, administration of DJ-1 protein reduced α-synuclein and hypoxia-inducible factor 1α mRNA and α-synuclein protein in MG-132 lesioned rats. Therefore, DJ-1 protein protected dopaminergic neurons in two PD model rats by increasing antioxidant capacity and inhibiting α-synuclein expression.