Lanthanum carbonate, a potent and selective phosphate binder, is transported and absorbed mainly via M cells in gastrointestinal tract

被引:3
|
作者
Huang, Hui-Xia [1 ]
Liu, Hui-Xue [1 ]
Yang, Xiao-Gai [1 ]
机构
[1] Peking Univ, Sch Pharmaceut Sci, Dept Chem Biol, Beijing 100191, Peoples R China
基金
中国国家自然科学基金;
关键词
gastrointestinal tract; lanthanum carbonate [La-2(CO3)(3); lanthanum phosphate (LaPO4); microfold cells; Peyer's patches; transportation and absorption; IN-VITRO MODEL; CALCIUM-PHOSPHATE; ORAL DELIVERY; NANOPARTICLES; DEPOSITION; EFFICACY; NECROSIS; THERAPY; SAFETY; IONS;
D O I
10.1093/mtomcs/mfad036
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This study aimed to investigate the transportation and absorption mechanism of lanthanum carbonate [La-2(CO3)(3)] through the gastrointestinal (GI) tract using in vitro and in vivo models. The results demonstrated that La-2(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 La-2(CO3)(3). Furthermore, oral administration of La-2(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 La-2(CO3)(3) caused a marked lanthanum accumulation in liver, accompanied by the activation of Kupffer cells. This study clarified how La-2(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.
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页数:12
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