Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Metallomics. 2023 Jun 1;15(6). doi: 10.1093/mtomcs/mfad036.
This study aimed to investigate the transportation and absorption mechanism of lanthanum carbonate [La2(CO3)3] through the gastrointestinal (GI) tract using in vitro and in vivo models. The results demonstrated that La2(CO3)3 can be dissolved in gastric fluids and precipitated into lanthanum phosphate as the main transformed specie in intestinal fluid. Using Caco-2 cell monoculture and Caco-2/Raji B cell coculture models to simulate the intestinal epithelium and microfold (M) cells, it was found that the amount of lanthanum transported in Caco-2/Raji B coculture model was significantly higher than that in Caco-2 monoculture model (about 50 times higher), indicating that M cells play an important role in the intestinal absorption of La2(CO3)3. Furthermore, oral administration of La2(CO3)3 to Balb/c mice demonstrated that lanthanum can be absorbed by both Peyer's patches (PPs) and non-PPs intestinal epithelium, with a higher amount of absorption in the PPs per unit weight. This finding further confirmed that the lanthanum absorption in GI tract could be mainly due to the contribution of M cells. Meanwhile, the administration of La2(CO3)3 caused a marked lanthanum accumulation in liver, accompanied by the activation of Kupffer cells. This study clarified how La2(CO3)3 is absorbed through the GI tract to enter the body and would be helpful to evaluate its potential biological consequences of accumulation in human beings.
本研究旨在利用体外和体内模型探究碳酸镧[La2(CO3)3]通过胃肠道(GI)的转运和吸收机制。结果表明,La2(CO3)3可溶解于胃液中,并在肠液中沉淀为主要转化产物磷酸镧。利用 Caco-2 细胞单层培养和 Caco-2/Raji B 细胞共培养模型模拟肠上皮和微褶皱(M)细胞,发现 Caco-2/Raji B 共培养模型中转运的镧量明显高于 Caco-2 单层培养模型(约高 50 倍),表明 M 细胞在 La2(CO3)3 的肠内吸收中起重要作用。此外,La2(CO3)3 经口给予 Balb/c 小鼠表明,镧可通过派尔集合淋巴结(PPs)和非 PPs 肠上皮吸收,单位重量 PPs 中的吸收量更高。这一发现进一步证实,GI 道中镧的吸收主要归因于 M 细胞的作用。同时,La2(CO3)3 的给予导致肝脏中明显的镧蓄积,并伴有枯否细胞的激活。本研究阐明了 La2(CO3)3 如何通过胃肠道吸收进入体内,并有助于评估其在人类体内蓄积的潜在生物学后果。