Therapeutic Effect of Lecithinized Superoxide Dismutase on Pulmonary Emphysema

Abstract

No medication exists that clearly improves the mortality of chronic obstructive pulmonary disease (COPD). Oxidative molecules, in particular superoxide anions, play important roles in the COPD-associated abnormal inflammatory response and pulmonary emphysema, which arises because of an imbalance in proteases and antiproteases and increased apoptosis. Superoxide dismutase (SOD) catalyzes the dismutation of superoxide anions. Lecithinized human Cu/Zn-SOD (PC-SOD) has overcome a number of the clinical limitations of SOD, including low tissue affinity and low stability in plasma. In this study, we examine the effect of PC-SOD on elastase-induced pulmonary emphysema, an animal model of COPD. The severity of the pulmonary inflammatory response and emphysema in mice was assessed by various criteria, such as the number of leukocytes in the bronchoalveolar lavage fluid and the enlargement of airspace. Not only intravenous administration but also inhalation of PC-SOD suppressed elastase-induced pulmonary inflammation, emphysema, and dysfunction. Inhalation of PC-SOD suppressed the elastase-induced increase in the pulmonary level of superoxide anions and apoptosis. Inhalation of PC-SOD also suppressed elastase-induced activation of proteases and decreased in the level of antiproteases and expression of proinflammatory cytokines and chemokines. We also found that inhalation of PC-SOD suppressed cigarette smokeinduced pulmonary inflammation. The results suggest that PC-SOD protects against pulmonary emphysema by decreasing the pulmonary level of superoxide anions, resulting in the inhibition of inflammation and apoptosis and amelioration of the protease/antiprotease imbalance. We propose that inhalation of PC-SOD would be therapeutically beneficial for COPD.

Mepenzolate bromide displays beneficial effects in a mouse model of chronic obstructive pulmonary disease

“…The level of superoxide anions was determined by ESR spin trapping with DPhPMPO 32,33 . Cells collected from BALF were incubated with 0.9% NaCl containing 500 mM diethylenetriamine-N, N, N 0 , N 00 , N 00 -pentaacetic acid and 10 mM DPhPMPO for 10 min at 37°C.…”

“…Determination of the FEV0.05/FVC ratio was performed with the same computer-controlled small-animal ventilator connected to a negative pressure reservoir (SCIREQ, Montreal, Canada) 32,33 . Mice were tracheotomized and ventilated as described above.…”

“…Measurement of lung mechanics and airway resistance was performed with a computer-controlled smallanimal ventilator (FlexiVent, SCIREQ, Montreal, Canada) 32,33 . Mice were anesthetized with chloral hydrate (500 mg kg À 1 ), a tracheotomy was performed, and an 8-mm section of metallic tube was inserted into the trachea.…”

Oxidative/Nitrosative Stress and the Pathobiology of Chronic Obstructive Pulmonary Disease

“…The limitations in the clinical use of superoxide dismutase include its low tissue affinity and low stability in plasma. However, these are likely to be overcome by employing the lecithinized enzyme, as has been documented by its efficacy in pre-clinical studies which have been done on COPD [63]. Further, antioxidant therapy has been found to be a complete cure for chronic pancreatitis [64].…”

Нозоспецифічні Особливості Редокс-Процесів При Бронхіальній Астмі Та Хронічній Обструктивній Хворобі Легень

“…Применение SOD-миметических средств или SOD-содержащих препаратов препятствует развитию эмфиземы легких [58]. Установлено, что у людей с полиморфизмом R213G гена ECSOD, кото-рый сопровождается очень высоким содержанием ECSOD (ее уровень в 10-20 раз выше, чем у людей без данного полиморфизма) в жидкости бронхоаль-веолярного лаважа и сыворотке крови, достоверно реже развивается ХОБЛ.…”