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Combined alpha‐tocopherol and ascorbic acid supplementation suppresses smoke‐induced lung squamous metaplasia in ferrets by preventing retinoic acid reduction
Author(s) -
Kim Yuri,
Chongviriyaphan Nalinee,
Liu Chun,
Russell Robert M.,
Wang XiangDong
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.977.10
Subject(s) - squamous metaplasia , retinoic acid , lung , ascorbic acid , metaplasia , chemistry , malondialdehyde , medicine , endocrinology , pharmacology , pathology , oxidative stress , biochemistry , epithelium , food science , gene
Previously we demonstrated that cigarette smoke exposure (CSE)‐induced lung lesions in ferrets were prevented by a combination of low dose of β‐carotene, α‐tocopherol (AT), and ascorbic acid (AA). However, the role of a combination of AT and AA alone in the protective effect on lung carcinogenesis remains to be examined. In the present study, we investigated whether the combined AT (equivalent to ~100 mg/day in the human) and AA (equivalent to ~210 mg/day) supplementation prevents against CSE (equivalent to 1.5 packs of cigarettes/day) induced lung squamous metaplasia in ferrets. Ferrets were treated for 6 weeks in the following three groups (9 ferrets/group): (i) Control (no CSE, no AT+AA), (ii) CSE, and (iii) CSE+AT+AA. Result showed that CSE significantly decreased concentrations of retinoic acid, AT, and reduced form of AA, not total AA and retinol, in the lungs of ferrets. Combined AT+AA treatment not only increased levels of AT and reduced AA, but also restored the lower concentration of retinoic acid in the lungs of CSE‐exposed ferrets to normal levels as the control group. Furthermore, the combined AT+AA supplementation prevented CSE‐induced squamous metaplasia and cyclin D1 expression in the lungs. Using HPLC analysis, we were unable to detect any difference on lung microsomal thiobarbituric acid‐malondialdehyde levels among the three groups. These data indicate that the combination of AT+AA alone exerts protective effects against CSE‐induced lung lesions by restoring retinoic acid levels to normal. This result could be due to their potential to prevent CSE‐induced retinoid acid degradation. (Supported by NIH grant R01CA104932 and USDA grant 1950‐51000‐064).