Department of Biomedical Sciences-Physiology, Faculty of Veterinary Medicine, Animal Health Institute (INDEGSAL), Campus de Vegazana, Universidad de León, 24071 León, Spain.
Int J Mol Sci. 2024 Sep 13;25(18):9884. doi: 10.3390/ijms25189884.
The ABCG2 membrane transporter affects bioavailability and milk secretion of xenobiotics and natural compounds, including vitamins such as riboflavin. We aimed to characterize the in vitro and in vivo interaction of ABCG2 with lumichrome, the main photodegradation product of riboflavin, which has proven in vitro anti-cancer activity and a therapeutical role in antibacterial photodynamic therapy as an efficient photosensitizer. Using MDCK-II polarized cells overexpressing murine Abcg2 and human ABCG2 we found that lumichrome was efficiently transported by both variants. After lumichrome administration to wild-type and Abcg2 mice, plasma AUC was 1.8-fold higher in Abcg2 mice compared with wild-type mice. The liver and testis from Abcg2 mice showed significantly higher lumichrome levels compared with wild-type, whereas lumichrome accumulation in small intestine content of wild-type mice was 2.7-fold higher than in Abcg2 counterparts. Finally, a 4.1-fold-higher lumichrome accumulation in milk of wild-type versus Abcg2 mice was found. Globally, our results show that ABCG2 plays a crucial role in plasma levels, tissue distribution and milk secretion of lumichrome potentially conditioning its biological activity.
ABCG2 膜转运蛋白会影响外源性和内源性化合物（包括维生素如核黄素）的生物利用度和乳汁分泌。我们旨在研究 ABCG2 与核黄素的主要光降解产物光黄素的体外和体内相互作用，光黄素已被证明具有体外抗癌活性，并在抗菌光动力疗法中作为一种有效的光敏剂发挥治疗作用。使用过表达鼠 Abcg2 和人 ABCG2 的 MDCK-II 极化细胞，我们发现两种变体都能有效地转运光黄素。在给予野生型和 Abcg2 小鼠光黄素后，Abcg2 小鼠的血浆 AUC 比野生型小鼠高 1.8 倍。与野生型相比，Abcg2 小鼠的肝脏和睾丸中的光黄素水平明显升高，而野生型小鼠小肠内容物中的光黄素积累则比 Abcg2 对应物高 2.7 倍。最后，我们发现野生型小鼠乳汁中的光黄素积累比 Abcg2 小鼠高 4.1 倍。总体而言，我们的结果表明 ABCG2 在光黄素的血浆水平、组织分布和乳汁分泌中起关键作用，这可能影响其生物学活性。
