Thyroid Hormone Regulates the Expression and Function of P-glycoprotein in Caco-2 Cells

Nishio, Naoki; Katsura, Toshiya; Inui, Ken Ichi

doi:10.1007/s11095-007-9495-x

Cited by 21 publications

(23 citation statements)

References 30 publications

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“…Similar P-gp overexpression during levothyroxine treatment was observed in the intestine and in the liver of hyperthyroid rats 9 and in human colon carcinoma cell lines. 10,11 Accordingly, levothyroxine cotreatment was hypothesized to affect oral disposition of P-gp substrates. 8 Significant decrease of oral bioavailability of cyclosporine A, by P-gp induction in intestine, was observed in an experimental rat model during levothyroxine cotreatment.…”

mentioning

confidence: 99%

“…10 However, despite the value of TPMT screening in reducing adverse drug reactions, TPMT status explains only 30%-60% of all cases with thiopurine intolerance. 11 Side effects other than myelotoxicity including flu-like symptoms, hepatotoxicity, pancreatitis, and dermatitis often result in discontinuation of therapy and are examples of adverse drug reactions, which cannot be explained by TPMT deficiency alone.…”

mentioning

confidence: 99%

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Linezolid Underexposure in a Hypothyroid Patient on Levothyroxine Replacement Therapy

Pea

Cadeo²,

Cojutti³

et al. 2014

Therapeutic Drug Monitoring

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mentioning

confidence: 99%

mentioning

confidence: 99%

Linezolid Underexposure in a Hypothyroid Patient on Levothyroxine Replacement Therapy

Pea

Cadeo²,

Cojutti³

et al. 2014

Therapeutic Drug Monitoring

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“…Whereas it has been known for a while that MRP2 is responsible for glycoside efflux (23), it has not been reported in literatures that addition of an additional glucose to flavonoid will result in change in the efflux transporter. The later is not a total surprise, however, as p-glycoprotein is shown to be responsible for the transport of digoxin, a triglycoside, in Caco-2 cells (25,26). On the other hand, BCRP remains to be the transporter partially responsible for the efflux of baohuoside I but not icariin, suggesting that the functions of efflux transporter BCRP is also sensitive to glycosidic structures of its substrates.…”

Section: Discussionmentioning

confidence: 99%

Intestinal Absorption Mechanisms of Prenylated Flavonoids Present in the Heat-Processed Epimedium koreanum Nakai (Yin Yanghuo)

et al. 2008

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Purpose-The purpose is to determine absorption mechanism of five bioactive prenylated flavonoids (baohuoside I, icariin, epimedine A, B, and C) present in heat-processed Epimedium koreanum Nakai (Yin Yanghuo).Methods-Transport of five prenylated flavonoids present in heat-processed herbs were studied in the human intestinal Caco-2 model and the perfused rat intestinal model.Results-In the perfused rat intestinal model, prenylated flavonoids with a monoglucosidic bond (e.g., icariin) was rapidly hydrolyzed into corresponding metabolites (e.g., baohuoside I). In the Caco-2 model, apical to basolateral permeability of a monoglycoside baohuoside I (1.46 ×10 −6 cm/ sec) was more than 2 folds greater than four prenylated flavonoids with 2 or more sugar moieties (<0.6×10 −6 cm/sec). The slow apical to basolateral transport of baohuoside I was the result of efflux. This efflux was carrier-mediated and active since its transport was vectorial, concentration-and temperature-dependent with activation energies greater than 15 kcal/mol. Efflux of baohuoside I was significantly suppressed by inhibitors of BCRP and MRP2, whereas efflux of icariin was significantly inhibited only by p-glycoprotein inhibitor verapamil. Because YHH is often heat-processed for better efficacy, we determined and found the optimal condition for increasing contents of more bioavailable flavonoids (i.e., baohuoside I) to be 160-170°C for 5-7 min.Conclusions-Poor bioavailability of prenylated flavonoids results from their poor intrinsic permeation and transporter-mediated efflux. Heat processing parameters may be optimized to preserve the herb's bioavailable flavonoids, which help retain and improve its efficacy during processing.

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“…9 Moreover, upregulation of P-gp was found to assist in the resistance of cancer cells toward antitumor drugs. 4,10 Thus, new drugs and dosage forms that inhibit P-gp expression should be explored. Gene regulation systems include small interfering RNAs (siRNA), microRNA (miRNA), and small hairpin RNAs (shRNA).…”

Section: Introductionmentioning

confidence: 99%

Binary-copolymer system base on low-density lipoprotein-coupled N-succinyl chitosan lipoic acid micelles for co-delivery MDR1 siRNA and paclitaxel, enhances antitumor effects via reducing drug

Yang

Zhu

et al. 2016

J. Biomed. Mater. Res.

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The development of effective and stable carriers of small interfering RNA (siRNA) is important for treating cancer with multidrug resistance (MDR). We developed a new gene and drug co-delivery system and checked its characteristics. Low-density lipoprotein (LDL) was coupled with N-succinyl chitosan (NSC) Lipoic acid (LA) micelles and co-delivered MDR1 siRNA and paclitaxel (PTX-siRNA/LDL-NSC-LA) to enhance antitumor effects by silencing the MDR gene of tumors (Li et al., Adv Mater 2014;26:8217-8224). In our study, we developed a new type of containing paclitaxel-loaded micelles and siRNA-loaded LDL nanoparticle. This "binary polymer" is pH and reduction dual-sensitive core-crosslinked micelles. PTX-siRNA/LDL-NSC-LA had an average particle size of (171.6 ± 6.42) nm, entrapment efficiency of (93.92 ± 1.06) %, and drug-loading amount of (12.35% ± 0.87) %. In vitro, MCF-7 cells, high expressed LDL receptor, were more sensitive to this delivery system than to taxol and cell activity was inhibited significantly. Fluorescence microscopy showed that PTX-siRNA/LDL-NSC-LA was uptaken very conveniently and played a key role in antitumor activity. PTX-siRNA/LDL-NSC-LA protected the siRNA from degradation by macrophage phagocytosis and evidently down-regulated the level of mdr1 mRNA as well as the expression of P-gp. We tested the target ability of PTX-siRNA/LDL-NSC-LA in vivo in tumor-bearing nude mice. Results showed that this system could directly deliver siRNA and PTX to cancer cells. Thus, new co-delivering siRNA and antitumor drugs should be explored for solving MDR in cancer. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1114-1125, 2017.

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Thyroid Hormone Regulates the Expression and Function of P-glycoprotein in Caco-2 Cells

Abstract: These results indicate that T(3) regulates the expression and function of Pgp. It is possible that changes in Pgp expression alter the pharmacokinetics of Pgp substrates in patients with thyroid disorders.

Cited by 21 publications

References 30 publications

Linezolid Underexposure in a Hypothyroid Patient on Levothyroxine Replacement Therapy

Linezolid Underexposure in a Hypothyroid Patient on Levothyroxine Replacement Therapy

Intestinal Absorption Mechanisms of Prenylated Flavonoids Present in the Heat-Processed Epimedium koreanum Nakai (Yin Yanghuo)

Binary-copolymer system base on low-density lipoprotein-coupled N-succinyl chitosan lipoic acid micelles for co-delivery MDR1 siRNA and paclitaxel, enhances antitumor effects via reducing drug

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