Beta-Cryptoxanthin attenuates cigarette smoke-induced lung lesions in the absence of carotenoid cleavage enzymes in mice

Authors: CHIAVERELLI, RACHEL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; HU, KANG-QUAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LIU, CHUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LIM, JI YE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DANIELS, MICHAEL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; XIA, HUI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MEIN, JONATHAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LINTIG, JOHANNES - Case Western Reserve University (CWRU); WANG, XIANG-DONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Molecules
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/24/2023
Publication Date: 1/29/2023
Citation: Chiaverelli, R.A., Hu, K., Liu, C., Lim, J., Daniels, M.S., Xia, H., Mein, J., Lintig, J.V., Wang, X. 2023. Beta-Cryptoxanthin attenuates cigarette smoke-induced lung lesions in the absence of carotenoid cleavage enzymes in mice. Molecules. https://doi.org/10.3390/molecules28031383.
DOI: https://doi.org/10.3390/molecules28031383

Interpretive Summary: High dietary intake of beta-cryptoxanthin, a provitamin A carotenoid found in red sweet peppers, butternut squash, and tangerines, is associated with a lower risk of lung disease. Beta-cryptoxanthin can be broken down by carotenoid cleavage enzymes to produce vitamin A and other metabolites. In the present study, using both animal and cell culture models, we demonstrated that beta-cryptoxanthin attenuated cigarette smoke-induced inflammatory lung lesion development. These data provided experimental evidence that dietary beta-cryptoxanthin could serve as an effective protective agent against lung disease in cigarette smokers.

Technical Abstract: High dietary intake of beta-cryptoxanthin (BCX, an oxygenated provitamin A carotenoid) is associated with a lower risk of lung disease in smokers. BCX can be cleaved by beta-carotene-15,150-oxygenase (BCO1) and beta-carotene-90,100-oxygenase (BCO2) to produce retinol and apo-100-carotenoids. We investigated whether BCX has protective effects against cigarette smoke (CS)-induced lung injury, dependent or independent of BCO1/BCO2 and their metabolites. Both BCO1-/-/BCO2-/- double knockout mice (DKO) and wild type (WT) littermates were supplemented with BCX 14 days and then exposed to CS for an additional 14 days. CS exposure significantly induced macrophage and neutrophil infiltration in the lung tissues of mice, regardless of genotypes, compared to the non-exposed littermates. BCX treatment significantly inhibited CS-induced inflammatory cell infiltration, hyperplasia in the bronchial epithelium, and enlarged alveolar airspaces in both WT and DKO mice, regardless of sex. The protective effects of BCX were associated with lower expression of IL-6, TNF-alpha, and matrix metalloproteinases-2 and -9. BCX treatment led to a significant increase in hepatic BCX levels in DKO mice, but not in WT mice, which had significant increase in hepatic retinol concentration. No apo-100-carotenoids were detected in any of the groups. In vitro BCX, at comparable doses of 3-OH-beta-apo-100-carotenal, was effective at inhibiting the lipopolysaccharide induced inflammatory response in a human bronchial epithelial cell line. These data indicate that BCX can serve as an effective protective agent against CS-induced lung lesions in the absence of carotenoid cleavage enzymes.