title: Potential role of ATP-binding cassette transporters in the intestinal transport of rhein.
abstract: Rhein, a lipophilic anthraquinone, exhibits anti-inflammatory and anti-tumor activities; however, it is hepatotoxic. ATP-binding cassette transporters, including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug resistance-associated protein 2 (MRP2), can pump toxicants from gut epithelial cells back into the intestinal lumen to prevent poisoning. We investigated their roles in rhein transport using a rat intestinal perfusion model and Caco-2, MDCKII-MDR1 (high expression of P-gp), MDCKII-BCRP (high expression of BCRP) and MDCKII-MRP2 (high expression of MRP2) cell models. The permeability of rhein in the duodenum significantly increased with increasing perfused concentration of rhein in the rat model, suggesting that efflux transporters were involved in rhein transport. In the Caco-2 cells, the permeability of rhein from the basolateral (B) to the apical (A) was significantly higher than that from A to B. In the presence of BCRP or MRP2 inhibitor, the permeability of rhein significantly decreased from B to A direction. In the MDCKII-BCRP cells, rhein was more permeable in B to A side than that in the opposite side. However, no significant differences of rhein permeability were observed in two directions in both MDCKII-MDR1 and MDCKII-MRP2 cells. Taken together, these results suggested that only BCRP was involved in rhein transport.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Ye
authors.forename: Linlin
authors.initials: L
authors.lastname: Lu
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.forename: Shan
authors.initials: S
authors.lastname: Zeng
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Yang
authors.forename: Weiying
authors.initials: W
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Lan
authors.initials: L
authors.lastname: Tang
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Liu
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000502:physiology*; D000818:Animals; D000880:Anthraquinones / Q000378:metabolism*; D001692:Biological Transport; D018938:Caco-2 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018528:ATP-Binding Cassette Transporters; D000880:Anthraquinones; C020491:rhein
keywords: A; ABC; ATP-binding cassette transporters; ATP-binding cassettet; B; BCRP; Caco-2 cell model; MDCKII; MRP2; Mardin–Darby canine kidney II; P-glycoprotein; P-gp; Rat intestinal perfusion model; Rhein; Transfected MDCKII cell model; apical; basolateral; breast cancer resistance protein; multidrug resistance-associated protein 2