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Scope β-Cryptoxanthin (BCX) can be cleaved by both β-carotene 15,15'-oxygenase (BCO1) and β-carotene 9',10'-oxygenase (BCO2), generating biological active vitamin A and apocarotenoids. We examined whether BCX feeding could inhibit diethylnitrosamine (DEN)-initiated, highly refined carbohydrate diet (HRCD)-promoted hepatocellular carcinoma (HCC) development, dependent or independent of BCO1/BCO2 activity. Methods and results Two-week-old male wild-type (WT) and BCO1-/- /BCO2-/- double knockout (DKO) mice are given a single intraperitoneal injection of DEN (25 mg kg-1 body weight) to initiate hepatic carcinogenesis. At 6 weeks of age, all animals are fed HRCD (66.5% of energy from carbohydrate) with or without BCX for 24 weeks. BCX feeding increases hepatic vitamin A levels in WT mice, but not in DKO mice that shows a significant accumulation of hepatic BCX. Compared to their respective HRCD littermates, both WT and DKO fed BCX have significantly lower HCC multiplicity, average tumor size, and total tumor volume, and the steatosis scores. The chemopreventive effects of BCX are associated with increased p53 protein acetylation and decreased protein levels of lactate dehydrogenase and hypoxia-inducible factor-1α in tumors. Conclusion This study suggests that BCX feeding may alleviate HRCD-promoted HCC progression by modulating the acetylation of p53, hypoxic tumor microenvironment, and glucose metabolism, independent of BCO1/BCO2.

cope β-Cryptoxanthin and astaxanthin are antioxidant carotenoid pigments that inhibit lipid peroxidation as potently as vitamin E. We hypothesized that acute treatment with β-cryptoxanthin and astaxanthin causes similar reductions in the sizes of cardiac infarcts caused by ischemia-reperfusion (I/R) injury by attenuating oxidative stress and cardiac mitochondrial dysfunction. Methods and results C57BL/6 mice (n = 36) were randomized to receive vehicle, β-cryptoxanthin, astaxanthin or vitamin E at 50 mg/kg by gavage feeding prior to I/R injury. Cardiac I/R was induced by left anterior descending coronary artery ligation followed by reperfusion. All treatments significantly reduced infarct sizes by 36–57%, attenuated apoptosis and also attenuated cardiac mitochondrial dysfunction in the treated groups compared to the control group. Although astaxanthin and vitamin E exhibited similar efficacy with respect to cardioprotection, β-cryptoxanthin exhibited greater efficacy than its counterparts, as it reduced infarct sizes by 60%. β-Cryptoxanthin was more effective than astaxanthin and vitamin E because it reduced cardiac mitochondrial swelling, mitochondrial depolarization, the Bax/Bcl-2 ratio and plasma and cardiac TBARS levels more significantly than its counterparts. Conclusion Acute β-cryptoxanthin treatment exhibits greater cardioprotective efficacy against I/R injury than astaxanthin and vitamin E by reducing infarct sizes and attenuating apoptosis, oxidative stress and mitochondrial dysfunction. This article is protected by copyright. All rights reserved

21 Páginas; 2 Tablas; 2 Figuras, Scope Carotenoids in human milk are associated with other lipid counterparts in several metabolic processes. One interesting association that has not been demonstrated to date is the presence of xanthophyll esters. Colostrum and mature milk samples were analyzed to determine the occurrence of xanthophyll esters and identify the compounds. Thus, the association of the amounts of these compounds with lactation and whether they are significant contributors to the carotenoid profile of human milk was assessed. Methods and results Pre-term and term delivering mothers were included in the study to donate colostrum at 3–5 days postpartum and mature milk at 15 days postpartum. Carotenoids extracts were subjected to a clean-up procedure to remove the triacylglycerol fraction and then analyzed by HPLC-MSn. Identification of xanthophyll esters was achieved by considering their chromatographic behaviour, UV-visible characteristics and MSn features. Conclusion Xanthophyll esters are significant contributors to the carotenoid profile in the colostrum, while mature milk does not contain these compounds. Therefore, fatty acid acylation to xanthophylls is activated during the accumulation of carotenoids in the human mammary gland. The sharp decline in the amount of xanthophyll esters in mature milk indicates that the lipophilic components are those recently incorporated in the mammary epithelium., The financial support of the Spanish Government is gratefully acknowledged (CICYT, Ministry of Economy and Competitiveness project AGL2013-42757-R).