Maciel Andressa A F L, Oriá Reinaldo B, Braga-Neto Manuel B, Braga Andréa B, Carvalho Eunice B, Lucena Herene B M, Brito Gerly A C, Guerrant Richard L, Lima Aldo A M
Clinical Research Unit & Institute of Biomedicine, School of Medicine, Federal University of Ceará, Brazil.
Toxicon. 2007 Dec 15;50(8):1027-40. doi: 10.1016/j.toxicon.2007.07.010. Epub 2007 Jul 31.
Vitamin A (retinol), a fat-soluble vitamin, is an essential nutrient for the normal functioning of the visual system, epithelial cell integrity and growth, immunity, and reproduction. Our group has investigated the effect of high doses of oral vitamin A on early childhood diarrhea in our prospective community-based studies from Northeast Brazil and found a beneficial role in reducing the mean duration but not incidence of diarrheal episodes. In this study, we explored the role of retinol supplementation in intestinal cell lines following Clostridium difficile toxin A (TxA) challenge. C. difficile is the most common anaerobic pathogen borne with antibiotic-borne diarrhea and pseudomembranous colitis. Since retinol is critical for the integrity of tight junctions and to modulate the cell cycle, we have focused on changes in transepithelial electrical resistance (TEER) in Caco-2, a more differentiated intestinal cell line, and on models of cell proliferation, migration and viability in IEC-6 cells, an undifferentiated crypt cell line, following TxA injury. In this model, retinol therapy reduced apoptosis, improved cell migration and proliferation, and prevented the reduction in TEER, following C. difficile TxA challenge in a glutamine-free medium. These results suggest the role of retinol in protecting intestinal epithelial barrier function from C. difficile TxA enterotoxic damage.
维生素A（视黄醇）是一种脂溶性维生素，是视觉系统正常运作、上皮细胞完整性与生长、免疫及生殖所必需的营养素。我们团队在巴西东北部开展的前瞻性社区研究中，调查了高剂量口服维生素A对幼儿腹泻的影响，发现其在缩短腹泻发作的平均持续时间而非发病率方面具有有益作用。在本研究中，我们探讨了补充视黄醇在艰难梭菌毒素A（TxA）攻击后肠道细胞系中的作用。艰难梭菌是抗生素相关性腹泻和伪膜性结肠炎最常见的厌氧病原体。由于视黄醇对于紧密连接的完整性以及调节细胞周期至关重要，我们重点研究了在TxA损伤后，更具分化性的肠道细胞系Caco-2中的跨上皮电阻（TEER）变化，以及未分化的隐窝细胞系IEC-6细胞中的细胞增殖、迁移和活力模型。在该模型中，在无谷氨酰胺培养基中经艰难梭菌TxA攻击后，视黄醇治疗可减少细胞凋亡，改善细胞迁移和增殖，并防止TEER降低。这些结果表明视黄醇在保护肠道上皮屏障功能免受艰难梭菌TxA肠毒素损伤方面的作用。
