State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, China.
J Pharmacol Sci. 2014;125(1):39-50. doi: 10.1254/jphs.13206fp. Epub 2014 Apr 16.
Oxidative stress is an important pathophysiological factor of asthma and chronic obstructive pulmonary disease (COPD). We hypothesized that procaterol and dexamethasone might treat inflammation through inhibiting oxidative stress in vitro. This study evaluated procaterol and dexamethasone in the hydrogen peroxide (H2O2)-induced immortal human bronchial epithelial cell model of oxidative stress and investigated the underlying mechanisms. Results showed that exposure to 125 μM H2O2 for 2 h led to a 50% reduction in the cell viability, significantly increased the percentage of apoptosis, and elevated levels of malondialdehyde and reactive oxygen species. Pretreatment with procaterol (25 - 200 nM) could reduce these effects in a dose-dependent manner. In contrast, pretreatment with dexamethasone (100 nM, 1000 nM) was inefficient. Pretreatment with procaterol plus dexamethasone (100 nM procaterol + 1000 nM dexamethasone) was effective, but the combined effect was not more effective than the sole pretreatment with 100 nM procaterol. The nuclear factor kappa-B (NF-κB) pathway was involved in the pathogenic mechanisms of H2O2. Procaterol may indirectly inhibit H2O2-induced activation of the NF-κB pathway due to its capability of antioxidation. Glucocorticoids may be not recommended to treat asthma or COPD complicated with severe oxidative stress.
氧化应激是哮喘和慢性阻塞性肺疾病（COPD）的重要病理生理因素。我们假设，普萘洛尔和地塞米松可能通过抑制体外氧化应激来治疗炎症。本研究评估了普萘洛尔和地塞米松在过氧化氢（H2O2）诱导的氧化应激体外人永生化支气管上皮细胞模型中的作用，并探讨了其潜在机制。结果表明，暴露于 125μM H2O2 2 小时导致细胞活力降低 50%，显著增加细胞凋亡率，并增加丙二醛和活性氧的水平。普萘洛尔（25-200 nM）预处理可呈剂量依赖性地降低这些作用。相比之下，地塞米松（100 nM，1000 nM）预处理无效。普萘洛尔加地塞米松（100 nM 普萘洛尔+1000 nM 地塞米松）预处理有效，但联合作用不如单独用 100 nM 普萘洛尔预处理有效。核因子 kappa-B（NF-κB）途径参与了 H2O2 的致病机制。由于其抗氧化能力，普萘洛尔可能间接抑制 H2O2 诱导的 NF-κB 途径的激活。糖皮质激素可能不建议用于治疗伴有严重氧化应激的哮喘或 COPD。
