Tomato Juice Keeps Emphysema From Developing In New Animal Model Of Degenerative Disease

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Lycopene -- cited in recent U.S. FDA action on tomato products and human prostate cancer --  is credited with positive results

BETHESDA, Md. (Jan. 10, 2006) – Feeding tomato juice to mice kept them from developing emphysema after cigarette smoke exposure that was long enough to induce emphysema in a control group, Japanese researchers report in February issue of the American Journal of Physiology-Lung Cellular and Molecular Physiology.

Researchers at Juntendo University School of Medicine first compared the reaction of two mostly similar mouse strains to inhaled cigarette smoke. Since the lungs of one of the mouse strains “naturally” age very quickly, the researchers believed that exposure to inhaled cigarette smoke would induce emphysema in that strain much more quickly than in the other strain. And indeed, they found that after eight weeks of breathing 1.5% tobacco smoke through the nose for 30 minutes a day, five days a week, the test strain, called SAMP1, did develop emphysema, while the control strain, called SAMR1, did not.

50% tomato juice drink “completely prevented” smoke-induced emphysema

Then, using the same experimental method, but substituting a 50% tomato juice mixture for their regular water supply, the researchers again compared the effect of smoking on the mice. They found that “smoke-induced emphysema was completely prevented by concomitant ingestion of lycopene (a potent antioxidant) given as tomato juice” in SAMP1 mice. They added: “Smoke exposure increased apoptosis and active caspase-3 of airway and alveolar septal cells and reduced VEGF in lung tissues, but tomato juice ingestion significantly reduced apoptosis and increased tissue VEGF level.”

The paper, “Tomato juice prevents senescence-accelerated mouse P1 strain from developing emphysema induced by chronic exposure to tobacco smoke,” appears in the February issue of the American Journal of Physiology-Lung Cellular and Molecular Physiology, published by the American Physiological Society. Research was performed by Satoshi Kasagi, Kuniaki Seyama, Hiroaki Mori, Sanae Souma, Tadashi Sato, Taeko Akiyoshi and Yoshinosuke Fukuchi at the Juntendo University School of Medicine, Tokyo, and Hiroyuki Suganuma of the Kagome Research Institute, Tochigi, Japan.

FDA questions if effect is from lycopene alone or tomato juice; Japanese concur

The tomato-lycopene link is made even more interesting because late last year the U.S. Food and Drug Administration gave permission for some tomato products to carry highly-qualified labeling claims linking men’s eating tomato products with a reduced incidence of prostate cancer. In reaching its decision, the FDA noted that it’s unclear whether lycopene alone is responsible for the tomato products’ effect.

Similarly, the Japanese researchers noted: “Since mice were given tomato juice instead of pure lycopene preparation, we can not exclude the possibility that other ingredients contained in tomato juice affected the results….”

Model for further study of pathophysiology and therapeutic intervention

Kuniaki Seyama, coauthor and project leader for the study, said: “The study demonstrated that the SAMP1 strain is a useful model for cigarette-smoke induced emphysema and a valuable tool to explore both pathophysiologic mechanisms and the effect of therapeutic intervention on smoke-induced emphysema.”

Seyama, who is an assistant professor at Juntendo, said the researchers started out to find a good animal model for studying smoking, which is a major health problem in Japan as well as globally. “The basic concept was to establish a mouse model. We looked at the senescence-accelerated mouse (SAM) because it reaches old age after normal development and maturation, and we believe that aging itself is an important component in emphysema.”

Lycopene used because it’s a naturally-occurring oxidant in food

Next, the researchers considered “what was the most important contributing factor in emphysema and we wanted to concentrate on oxidative stress for two reasons,” Seyama said.  “First is because the consequences of oxidative stress during life is considered to be deeply involved in the aging process. And second, tobacco smoke contains lots of oxidants and hence puts oxidative stress on the lungs. Using our mouse model for smoke-induced emphysema, we wanted to intervene in the accumulation process by changing daily lifestyle, especially eating habits, “Seyama said. Looking for a natural antioxidant in food, “we thought lycopene might be a good candidate,” he added.

However, Seyama (and the AJP-Lung paper Kasagi et al.) cautioned: “We can’t simply accept that these results go beyond the mouse model. They are not so smoothly applied to human beings,” Seyama noted.

Next steps

• The team would like to test how tomato juice ingestion might affect human patients with COPD (chronic obstructive lung disease), Seyama said.

• Since overall, the researchers are interested in the mechanisms of nutrients in development of human disease and lifestyle, this study could lead in several other directions, he added.

Source and funding

The paper, “Tomato juice prevents senescence-accelerated mouse P1 strain from developing emphysema induced by chronic exposure to tobacco smoke,” appears online in the American Journal of Physiology-Lung Cellular and Molecular Physiology, published by the American Physiological Society. Research was performed by Satoshi Kasagi, Kuniaki Seyama, Hiroaki Mori, Sanae Souma, Tadashi Sato, Taeko Akiyoshi and Yoshinosuke Fukuchi, at the Department of Respiratory Medicine at the Juntendo University School of Medicine, Tokyo, and Hiroyuki Suganuma of the Kagome Research Institute, Kagome Co., Tochigi, Japan.

This study was supported by Grants-in-Aid for Scientific Research (Fukuchi) and a High Technology Research Center Grant, all from the Japanese Ministry of Education, Culture, Sports, Science and Technology; and by the Institute for Environment and Gender-Specific Medicine of Juntendo University Graduate School of Medicine.

Kagome Co., Tokyo, is a leader in tomato cultivation and a major producer of fruit and vegetable processed foods. Kagome provided the tomato juice for the experiments.

Editor’s note: The media may obtain a copy of Kasagi et al. by contacting Donna Krupa, American Physiological Society, (301) 634-7209, cell (703) 967-2751 or dkrupa@the-aps.org.

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The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has more than 10,000 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.

APS  provides a wide range of research, educational and career support and programming to further the contributions of physiology to understanding the mechanisms of diseased and healthy states. In May 2004, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring (PAESMEM).

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