Therapeutic effect of lecithinized superoxide dismutase on pulmonary emphysema

Ken Ichiro Tanaka, Yuta Tanaka, Yuri Miyazaki, Takushi Namba, Keizo Sato, Kazutetsu Aoshiba, Arata Azuma, Tohru Mizushima

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 smoke-induced 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.

Original languageEnglish
Pages (from-to)810-818
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume338
Issue number3
DOIs
Publication statusPublished - 2011 Sep
Externally publishedYes

Fingerprint

Pulmonary Emphysema
Therapeutic Uses
Superoxide Dismutase
Inhalation
Pancreatic Elastase
Superoxides
Chronic Obstructive Pulmonary Disease
Protease Inhibitors
Peptide Hydrolases
Apoptosis
Lung
Pneumonia
lecithinized superoxide dismutase
Emphysema
Bronchoalveolar Lavage Fluid
Leukocyte Count
Chemokines
Smoke
Tobacco Products
Intravenous Administration

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

Tanaka, K. I., Tanaka, Y., Miyazaki, Y., Namba, T., Sato, K., Aoshiba, K., ... Mizushima, T. (2011). Therapeutic effect of lecithinized superoxide dismutase on pulmonary emphysema. Journal of Pharmacology and Experimental Therapeutics, 338(3), 810-818. https://doi.org/10.1124/jpet.111.179051

Therapeutic effect of lecithinized superoxide dismutase on pulmonary emphysema. / Tanaka, Ken Ichiro; Tanaka, Yuta; Miyazaki, Yuri; Namba, Takushi; Sato, Keizo; Aoshiba, Kazutetsu; Azuma, Arata; Mizushima, Tohru.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 338, No. 3, 09.2011, p. 810-818.

Research output: Contribution to journalArticle

Tanaka, KI, Tanaka, Y, Miyazaki, Y, Namba, T, Sato, K, Aoshiba, K, Azuma, A & Mizushima, T 2011, 'Therapeutic effect of lecithinized superoxide dismutase on pulmonary emphysema', Journal of Pharmacology and Experimental Therapeutics, vol. 338, no. 3, pp. 810-818. https://doi.org/10.1124/jpet.111.179051
Tanaka, Ken Ichiro ; Tanaka, Yuta ; Miyazaki, Yuri ; Namba, Takushi ; Sato, Keizo ; Aoshiba, Kazutetsu ; Azuma, Arata ; Mizushima, Tohru. / Therapeutic effect of lecithinized superoxide dismutase on pulmonary emphysema. In: Journal of Pharmacology and Experimental Therapeutics. 2011 ; Vol. 338, No. 3. pp. 810-818.
@article{dc94c71bf574463ab33483a2624a3085,
title = "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 smoke-induced 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.",
author = "Tanaka, {Ken Ichiro} and Yuta Tanaka and Yuri Miyazaki and Takushi Namba and Keizo Sato and Kazutetsu Aoshiba and Arata Azuma and Tohru Mizushima",
year = "2011",
month = "9",
doi = "10.1124/jpet.111.179051",
language = "English",
volume = "338",
pages = "810--818",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TY - JOUR

T1 - Therapeutic effect of lecithinized superoxide dismutase on pulmonary emphysema

AU - Tanaka, Ken Ichiro

AU - Tanaka, Yuta

AU - Miyazaki, Yuri

AU - Namba, Takushi

AU - Sato, Keizo

AU - Aoshiba, Kazutetsu

AU - Azuma, Arata

AU - Mizushima, Tohru

PY - 2011/9

Y1 - 2011/9

N2 - 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 smoke-induced 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.

AB - 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 smoke-induced 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.

UR - http://www.scopus.com/inward/record.url?scp=80052154581&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052154581&partnerID=8YFLogxK

U2 - 10.1124/jpet.111.179051

DO - 10.1124/jpet.111.179051

M3 - Article

VL - 338

SP - 810

EP - 818

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 3

ER -