A research group consisting of graduate student Hiroaki Kubo, Associate Professor Kazuhisa Asai and Professor Tomoya Kawaguchi, et al. of the Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University has shown that the antioxidant, Astaxanthin, contained in crustaceans such as crabs, shrimp, and salmon helps prevent emphysema - one kind of Chronic Obstructive Pulmonary Disease (COPD).　

COPD affects more than 5 million people in Japan.? Emphysema, in particular is caused by inhaling cigarette smoke, which destroys air sacs in the lungs called alveoli. As emphysema progresses, cough, sputum and shortness of breath occur, and as a result home oxygen therapy^*1 is required for some patients. COPD-related deaths like emphysema are increasing year by year and is reported to be the third leading cause of death world-wide.

At present there is no effective treatment to repair lungs damaged by cigarette smoke. Not smoking and bronchodilators are the main forms of treatment. The research group under Associate Professor Asai, et al. found that by administering astaxanthin to mice exposed to cigarette smoke, increased antioxidant capacity and suppressed symptoms of emphysema in lung tissue. It was the first research of its kind to find a correlation between astaxanthin and the suppression of symptoms of emphysema. It has shown empirically the preventative effects of astaxanthin and show that it has the potential to be a novel therapeutic strategy for all COPD.

The results of this research were published online in the international science journal “Marine drugs” on 28 November, 2019 (Japan time).

^*1Installing equipment to supply oxygen at home at a density level that is higher than the air in the room.

【Publishing journal】Marine Drugs（IF=3.772）
【Paper title】Astaxanthin suppresses cigarette smoke-induced emphysema through Nrf2 activation in mice
【Authors】Hiroaki Kubo, Kazuhisa Asai, Kazuya Kojima, Arata Sugitani,
Yohkoh Kyomoto,Atsuko Okamoto, Kazuhiro Yamada, Naoki Ijiri, Tetsuya Watanabe, Kazuto Hirata and Tomoya Kawaguchi
【Publishing URL】https://www.mdpi.com/1660-3397/17/12/673

Research Background

COPD is caused by long-term inhalation of harmful gases such as cigarette smoke. Cigarette smoke contains many harmful substances including reactive oxygen species(ROS)^*2. Oxidative stress is the result of the body having an excessive amount of reactive oxygen species and is part of the pathogenesis of COPD. On the other hand, ROS are also known to trigger a defense mechanism against oxidative stress by activating the transcription factor^*3 Nrf2 (Nuclear factor erythroid 2-relted factor 2) in vivo studies.

Astaxanthin is an orange-red pigment found in crustaceans such as crabs, shrimp, and salmon. It is a kind of a carotenoid, same as lycopene and β-carotene. It is a powerful antioxygen substance that is said to be approximately 6000 times more powerful than vitamin C and 800 times more powerful than coenzyme Q10. Recent studies have shown that astaxanthin protects in vivo test subjects from oxidative stress by activating Nrf2. Based on these reports Associate Professor Asai‘s research group hypothesized that astaxanthin could increase Nrf2 occurrence in the lung, reduce oxidative stress, and decrease emphysema caused by cigarette smoke.

^*2Molecules derived from oxygen which react with biopolymers such as DNA, lipids, proteins and enzymes in vivo, resulting in lipid peroxidation, DNA mutation, protein denaturation, enzyme inactivation.

^*3Proteins that specifically bind to DNA.

Content of Research

In the study, mice were exposed to cigarette smoke for 12 weeks, and the effect a diet with and without astaxanthin had on COPD pathology was examined. In the astaxanthin-administered group, the expression of Nrf2 and antioxidant protein HO-1 (Heme oxygenase-1) in lung tissue was significantly increased [Fig. 1], and the number of inflammatory cells in BALF (bronchoalveolar lavage fluid) (Macrophages and neutrophils) were significantly decreased [Fig. 2], and MLI (mean linear intercept) indicating the degree of emphysema and destructive index indicating the degree of alveolar destruction were suppressed [Figure 3].

Fig. 1 Expression of Nrf2 and antioxidant protein HO-1 in lung tissue

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Expected Effect

This study shows that astaxanthin increases antioxidant capacity in lung tissue and prevents emphysema. Astaxanthin is attracting attention as a new candidate substance for COPD treatments.

Research funds

This is part of the Grants-in-Aid for Scientific Research C (19K08660).
Astaxanthin - FUJIFILM Astaxanthin 10O provided by FUJIFILM is used in this research.