Modulation of expression and activity of intestinal multidrug resistance-associated protein 2 by xenobiotics

Tocchetti, Guillermo Nicolás; Rigalli, Juan Pablo; Arana, Maite Rocío; Villanueva, Silvina Stella Maris; Mottino, Aldo D.

doi:10.1016/j.taap.2016.05.002

Cited by 24 publications

(14 citation statements)

References 112 publications

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“…The results pointed to a diverse range of ligands including pesticides, flame retardants, oil hydrocarbons, stain repellents, personal [20,201,[217][218][219][220][221][222][223][224][225]. (B) Blood-intestine barrier [10,20,201,[225][226][227][228]. (C) Blood-milk barrier in mammary glands [229][230][231].…”

Section: Introduction-evolution and Function Of The Small Molecule Trmentioning

confidence: 99%

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Disruption of small molecule transporter systems by Transporter‐Interfering Chemicals (TICs)

Nicklisch

Hamdoun

2020

FEBS Letters

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Small molecule transporters (SMTs) in the ABC and SLC families are important players in disposition of diverse endo-and xenobiotics. Interactions of environmental chemicals with these transporters were first postulated in the 1990s, and since validated in numerous in vitro and in vivo scenarios. Recent results on the co-crystal structure of ABCB1 with the flame-retardant BDE-100 demonstrate that a diverse range of man-made and natural toxic molecules, hereafter termed transporter-interfering chemicals (TICs), can directly bind to SMTs and interfere with their function. TIC-binding modes mimic those of substrates, inhibitors, modulators, inducers, and possibly stimulants through direct and allosteric mechanisms. Similarly, the effects could directly or indirectly agonize, antagonize or perhaps even prime the SMT system to alter transport function. Importantly, TICs are distinguished from drugs and pharmaceuticals that interact with transporters in that exposure is unintended and inherently variant. Here, we review the molecular mechanisms of environmental chemical interaction with SMTs, the methodological considerations for their evaluation, and the future directions for TIC discovery.

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Section: Introduction-evolution and Function Of The Small Molecule Trmentioning

confidence: 99%

“…(A) Blood–brain barrier and blood–cerebrospinal fluid barrier [20,201,217–225]. (B) Blood–intestine barrier [10,20,201,225–228]. (C) Blood–milk barrier in mammary glands [229–231].…”

Section: Introduction–evolution and Function Of The Small Molecule Trmentioning

confidence: 99%

Disruption of small molecule transporter systems by Transporter‐Interfering Chemicals (TICs)

Nicklisch

Hamdoun

2020

FEBS Letters

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“…Lactobacillus plantarum, L. brevis and L. bulgaricus mitigate the effect of enrofloxacin on expression of ABCC2 mRNA in the liver because its down-regulation provoked by the fluoroquinolone was significant only in comparison to the group supplemented with probiotics plus enrofloxacin. Altogether these data demonstrate that lactobacilli and enrofloxacin are among dietary additives and drugs, respectively that are capable to regulate transcriptionally intestinal MRP2 expression (Tocchetti et al, 2016). Administration of probiotics cannot be associated with changes in ABCC2 mRNA levels which can be observed during inflammation and thus may have positive effect in maintenance of health in the gastro-intestinal tract.…”

Section: Discussionmentioning

confidence: 83%

“…Administration of Lactobacillus plantarum, L. brevis and L. bulgaricus and addition of enrofloxacin to probiotics as well as treatment with the enrofloxacin only, resulted in pronounced statistically significant decrease of ABCC2 mRNA levels in the duodenum. These changes can contribute to hindering the efflux of glucuronides and other conjugates as well as bile acids in the upper part of small intestines and at the same time can decrease the transport of mediators promoting inflammation (Tocchetti et al, 2016). The effect of probiotics administered with or without enrofloxacin on the levels of ABCC2 mRNA in the duodenum of healthy broilers differs from the observed changes in inflamed tissues.…”

Section: Discussionmentioning

confidence: 97%

Effect of treatment with enrofloxacin and Lactobacillus probiotics on ABCB1, ABCC2 and ABCG2 mRNA expression in poultry

Павлова¹,

Yordanova²,

Danova³

et al. 2018

BJVM

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Poultry feed is often supplemented by Lactobacillus probiotics which may alter drug bioavailability by affecting the expression of intestinal ATP-binding cassette (ABC) efflux transporters. Therefore the effect of probiotics, administered alone or in combination with enrofloxacin, on the expression of ABCB1, ABCC2 and ABCG2 mRNAs in chickens was evaluated. Day-old Ross chicks (n=24) were divided in four equal groups. Control group was not treated. The second group received feed with addition of probiotics Lactobacillus brevis, L. plantarum and L. bulgaricus 5 days after hatching, for 15 days. The third group received probiotics as described above and enrofloxacin at the age of 15 days (10 mg/kg, via drinking water for 5 days). The last group received enrofloxacin at age of 15 days (10 mg/kg, via drinking water for 5 days). Expression of ABC transporters in liver, duodenum and jejunum was determined by qRT-PCR. Down-regulation of ABCG2 mRNA in the liver (P<0.05), its up-regulation in the duodenum (P<0.05) and increased ABCB1 mRNA levels in the jejunum (P<0.05) can be attributed to enrofloxacin treatment. Decrease in ABCC2 mRNA expression in the duodenum can be associated with enrofloxacin administration. The observed changes were related to enrofloxacin administration and to lesser extent to Lactobacillus supplementation.

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“…MRP2 is localized at the apical membrane of enterocytes in the intestine and plays a key role in limiting the absorption of substrate drugs incorporated orally. In the liver, MRP2 localizes to the canalicular membrane of hepatocytes and mediates the efflux of substrate drugs into the bile 26 .…”

Section: Discussionmentioning

confidence: 99%

Influence of CYP3A4/5 and ABC transporter polymorphisms on lenvatinib plasma trough concentrations in Japanese patients with thyroid cancer

Ozeki

Nagahama

Fujita

et al. 2019

Sci Rep

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Lenvatinib is a substrate of cytochrome P450 (CYP) 3A and ATP-binding cassette (ABC) transporters. In this study, we aimed to evaluate how CYP3A4/5 and ABC transporter polymorphisms affected the mean steady-state dose-adjusted plasma trough concentrations (C 0 ) of lenvatinib in a cohort of 40 Japanese patients with thyroid cancer. CYP3A4 20230G > A ( *1G ), CYP3A5 6986A > G ( *3 ), ABCB1 1236C > T, ABCB1 2677G > T/A, ABCB1 3435C > T, ABCC2 −24C > T, and ABCG2 421C > A genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism. In univariate analysis, there were no significant differences in the mean dose-adjusted C 0 values of lenvatinib between the ABCB1 , ABCG2 , and CYP3A5 genotypes. However, the mean dose-adjusted C 0 values of lenvatinib in patients with the CYP3A4*1/*1 genotype and ABCC2 −24T allele were significantly higher than those in patients with the CYP3A4*1G allele and −24C/C genotype, respectively ( P = 0.018 and 0.036, respectively). In multivariate analysis, CYP3A4 genotype and total bilirubin were independent factors influencing the dose-adjusted C 0 of lenvatinib ( P = 0.010 and 0.046, respectively). No significant differences were found in the incidence rates of hypertension, proteinuria, and hand-foot syndrome following treatment with lenvatinib between the genotypes of CYP3A4/5 and ABC transporters. Lenvatinib pharmacokinetics were significantly influenced by the CYP3A4*1G polymorphism. If the target plasma concentration of lenvatinib for efficacy or toxicity is determined, elucidation of the details of the CYP3A4*1G genotype may facilitate decision-making related to the appropriate initial lenvatinib dosage to achieve optimal plasma concentrations.

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Modulation of expression and activity of intestinal multidrug resistance-associated protein 2 by xenobiotics

Cited by 24 publications

References 112 publications

Disruption of small molecule transporter systems by Transporter‐Interfering Chemicals (TICs)

Disruption of small molecule transporter systems by Transporter‐Interfering Chemicals (TICs)

Effect of treatment with enrofloxacin and Lactobacillus probiotics on ABCB1, ABCC2 and ABCG2 mRNA expression in poultry

Influence of CYP3A4/5 and ABC transporter polymorphisms on lenvatinib plasma trough concentrations in Japanese patients with thyroid cancer

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