Drugs interacting with organic anion transporter-1 affect uptake of Tc-99m-mercaptoacetyl-triglycine (MAG3) in the human kidney: Therapeutic drug interaction in Tc-99m-MAG3 diagnosis of renal function and possible application of Tc-99m-MAG3 for drug development

Obesity is health issue worldwide, which can lead to kidney dysfunction. Prebiotics are non-digestible foods that have beneficial effects on health. This study aimed to investigate the effects of xylooligosaccharide (XOS) on renal function, renal organic anion transporter 3 (Oat3) and the mechanisms involved. High-fat diet was provided for 12 weeks in male Wistar rats. After that, the rats were divided into normal diet (ND); normal diet treated with XOS (NDX); high-fat diet (HF) and high-fat diet treated with XOS (HFX). XOS was given daily at a dose of 1000 mg for 12 weeks. At week 24, HF rats showed a significant increase in obesity and insulin resistance associated with podocyte injury, increased microalbuminuria, decreased creatinine clearance and impaired Oat3 function. These alterations were improved by XOS supplementation. Renal MDA level and the expression of AT1R, NOX4, p67phox, 4-HNE, phosphorylated PKCα and ERK1/2 were significantly decreased after XOS treatment. In addition, Nrf2-Keap1 pathway, SOD2 and GCLC expression as well as renal apoptosis were also significantly reduced by XOS. These data suggest that XOS could indirectly restore renal function and Oat3 function via the reduction of oxidative stress and apoptosis through the modulating of AT1R-PKCα-NOXs activation in obese insulin-resistant rats. These attenuations were instigated by the improvement of obesity, hyperlipidemia and insulin resistance.

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Renal Organic Anion Transporter-Mediated Drug-Drug Interaction between Gemcabene and Quinapril

Journal of Pharmacology and Experimental Therapeutics ◽

10.1124/jpet.108.149476 ◽

2009 ◽

Vol 330 (1) ◽

pp. 191-197 ◽

Cited By ~ 28

Author(s):

Haodan Yuan ◽

Bo Feng ◽

Ying Yu ◽

Jonathan Chupka ◽

Jenny Y. Zheng ◽

...

Keyword(s):

Drug Interaction ◽

Organic Anion ◽

Organic Anion Transporter ◽

Anion Transporter ◽

Drug Drug Interaction

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The key role of organic anion transporter 3 in the drug–drug interaction between tranilast and methotrexate

Journal of Biochemical and Molecular Toxicology ◽

10.1002/jbt.22983 ◽

2022 ◽

Author(s):

Jingjing Wang ◽

Wenjing Yuan ◽

Qingqing Shen ◽

Qipeng Wu ◽

Zhenzhou Jiang ◽

...

Keyword(s):

Drug Interaction ◽

Organic Anion ◽

Organic Anion Transporter ◽

Anion Transporter ◽

Drug Drug Interaction ◽

Organic Anion Transporter 3

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Transport of cimetidine by flounder and human renal organic anion transporter 1

AJP Renal Physiology ◽

10.1152/ajprenal.00290.2002 ◽

2003 ◽

Vol 284 (3) ◽

pp. F503-F509 ◽

Cited By ~ 30

Author(s):

Birgitta C. Burckhardt ◽

Stefan Brai ◽

Sönke Wallis ◽

Wolfgang Krick ◽

Natascha A. Wolff ◽

...

Keyword(s):

Organic Anion ◽

Human Kidney ◽

Organic Anion Transporter ◽

In Vivo Studies ◽

Xenopus Laevis Oocytes ◽

Organic Anion Transporters ◽

Anion Transporters ◽

Anion Transporter ◽

Inward Currents

The H2-receptor antagonist cimetidine is efficiently excreted by the kidneys. In vivo studies indicated an interaction of cimetidine not only with transporters for basolateral uptake of organic cations but also with those involved in excretion of organic anions. We therefore tested cimetidine as a possible substrate of the organic anion transporters cloned from winter flounder (fROAT) and from human kidney (hOAT1). Uptake of [3H]cimetidine into fROAT-expressing Xenopus laevis oocytes exceeded uptake into control oocytes. At −60-mV clamp potential, 1 mM cimetidine induced an inward current, which was smaller than that elicited by 0.1 mM PAH. Cimetidine concentrations exceeding 0.1 mM decreased PAH-induced inward currents, indicating interaction with the same transporter. At pH 6.6, no current was seen with 0.1 mM cimetidine, whereas at pH 8.6 a current was readily detectable, suggesting preferential translocation of uncharged cimetidine by fROAT. Oocytes expressing hOAT1 also showed [3H]cimetidine uptake. These data reveal cimetidine as a substrate for fROAT/hOAT1 and suggest that organic anion transporters contribute to cimetidine excretion in proximal tubules.

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Involvement of Organic Anion Transporters in the Pharmacokinetics and Drug Interaction of Rosmarinic Acid

Pharmaceutics ◽

10.3390/pharmaceutics13010083 ◽

2021 ◽

Vol 13 (1) ◽

pp. 83

Author(s):

Yun Ju Kang ◽

Chul Haeng Lee ◽

Soo-Jin Park ◽

Hye Suk Lee ◽

Min-Koo Choi ◽

...

Keyword(s):

Drug Interaction ◽

Rosmarinic Acid ◽

Renal Excretion ◽

Organic Anion ◽

Plasma Concentrations ◽

Pharmacokinetic Interaction ◽

Organic Anion Transporter ◽

Hek293 Cells ◽

Anion Transporter

We investigated the involvement of drug transporters in the pharmacokinetics of rosmarinic acid in rats as well as the transporter-mediated drug interaction potential of rosmarinic acid in HEK293 cells overexpressing clinically important solute carrier transporters and also in rats. Intravenously injected rosmarinic acid showed bi-exponential decay and unchanged rosmarinic acid was mainly eliminated by urinary excretion, suggesting the involvement of transporters in its renal excretion. Rosmarinic acid showed organic anion transporter (OAT)1-mediated active transport with a Km of 26.5 μM and a Vmax of 69.0 pmol/min in HEK293 cells overexpressing OAT1, and the plasma concentrations of rosmarinic acid were increased by the co-injection of probenecid because of decreased renal excretion due to OAT1 inhibition. Rosmarinic acid inhibited the transport activities of OAT1, OAT3, organic anion transporting polypeptide (OATP)1B1, and OATP1B3 with IC50 values of 60.6 μM, 1.52 μM, 74.8 μM, and 91.3 μM, respectively, and the inhibitory effect of rosmarinic acid on OAT3 transport activity caused an in vivo pharmacokinetic interaction with furosemide by inhibiting its renal excretion and by increasing its plasma concentration. In conclusion, OAT1 and OAT3 are the major transporters that may regulate the pharmacokinetic properties of rosmarinic acid and may cause herb-drug interactions with rosmarinic acid, although their clinical relevance awaits further evaluation.

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Organic anion transporter 3 (OAT3)-mediated transport of dicaffeoylquinic acids and prediction of potential drug-drug interaction

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2019.03.022 ◽

2019 ◽

Vol 133 ◽

pp. 95-103 ◽

Cited By ~ 4

Author(s):

Yan Wang ◽

Jianting Ren ◽

Qingquan Sun ◽

Zhanjun Zhang ◽

Yanhe Lin ◽

...

Keyword(s):

Drug Interaction ◽

Organic Anion ◽

Organic Anion Transporter ◽

Potential Drug ◽

Anion Transporter ◽

Drug Drug Interaction ◽

Organic Anion Transporter 3

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Effect of erythropoietin on mercury-induced nephrotoxicity: Role of membrane transporters

Human & Experimental Toxicology ◽

10.1177/0960327120958109 ◽

2020 ◽

pp. 096032712095810

Author(s):

MH Hazelhoff ◽

AM Torres

Keyword(s):

Renal Function ◽

Organic Anion ◽

Absorption Spectrometry ◽

Renal Tissue ◽

Mercury Content ◽

Organic Anion Transporter ◽

Tubular Injury ◽

Human Erythropoietin ◽

Anion Transporter ◽

Renal Expression

Mercury is a widespread pollutant. Mercuric ions uptake into tubular cells is supported by the Organic anion transporter 1 (Oat1) and 3 (Oat3) and its elimination into urine is through the Multidrug resistance-associated protein 2 (Mrp2). We investigated the effect of recombinant human erythropoietin (Epo) on renal function and on renal expression of Oat1, Oat3, and Mrp2 in a model of mercuric chloride (HgCl2)-induced renal damage. Four experimental groups of adult male Wistar rats were used: Control, Epo, HgCl2, and Epo + HgCl2. Epo (3000 IU/kg, b.w., i.p.) was administered 24 h before HgCl2 (4 mg/kg, b.w., i.p.). Experiments were performed 18 h after the HgCl2 dose. Parameters of renal function and structure were evaluated. The protein expression of Oat1, Oat3 and Mrp2 in renal tissue was assessed by immunoblotting techniques. Mercury levels were determined by cold vapor atomic absorption spectrometry. Pretreatment with Epo ameliorated the HgCl2-induced tubular injury as assessed by histopathology and urinary biomarkers. Immunoblotting showed that pretreatment with Epo regulated the renal expression of mercury transporters in a way to decrease mercury content in the kidney. Epo pretreatment ameliorates HgCl2-induced renal tubular injury by modulation of mercury transporters expression in the kidneys.

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