770 results match your criteria inhibition probenecid


Pleiotropic effects of probenecid on three-dimensional cultures of prostate cancer cells.

Life Sci 2021 Apr 28;278:119554. Epub 2021 Apr 28.

Department of Biochemistry, Asahikawa Medical University, Asahikawa 078-8510, Japan.

Aims: Chemoresistance remains a persistent challenge in advanced prostate cancer therapy. Probenecid reportedly inhibits multiple drug-efflux transporters; hence, it can be employed as a potential sensitizer for chemotherapy. In the present study, we evaluated the effects of probenecid on three-dimensional (3D)-cultures of prostate cancer cells. Read More

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Clinical Investigation on Endogenous Biomarkers to Predict Strong OAT-Mediated Drug-Drug Interactions.

Clin Pharmacokinet 2021 Apr 10. Epub 2021 Apr 10.

Drug Metabolism and Pharmacokinetics, Janssen Pharmaceutical Companies of Johnson & Johnson, Turnhoutseweg 30, 2340, Beerse, Belgium.

Background: Endogenous biomarkers are promising tools to assess transporter-mediated drug-drug interactions early in humans.

Methods: We evaluated on a common and validated in vitro system the selectivity of 4-pyridoxic acid (PDA), homovanillic acid (HVA), glycochenodeoxycholate-3-sulphate (GCDCA-S) and taurine towards different renal transporters, including multidrug resistance-associated protein, and assessed the in vivo biomarker sensitivity towards the strong organic anion transporter (OAT) inhibitor probenecid at 500 mg every 6 h to reach close to complete OAT inhibition.

Results: PDA and HVA were substrates of the OAT1/2/3, OAT4 (PDA only) and multidrug resistance-associated protein 4; GCDCA-S was more selective, having affinity only towards OAT3 and multidrug resistance-associated protein 2. Read More

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Structural and Functional Characterization of the ABCC6 Transporter in Hepatic Cells: Role on PXE, Cancer Therapy and Drug Resistance.

Int J Mol Sci 2021 Mar 11;22(6). Epub 2021 Mar 11.

Department of Sciences, University of Basilicata, 85100 Potenza, Italy.

Pseudoxanthoma elasticum (PXE) is a complex autosomal recessive disease caused by mutations of ABCC6 transporter and characterized by ectopic mineralization of soft connective tissues. Compared to the other ABC transporters, very few studies are available to explain the structural components and working of a full ABCC6 transporter, which may provide some idea about its physiological role in humans. Some studies suggest that mutations of in the liver lead to a decrease in some circulating factor and indicate that PXE is a metabolic disease. Read More

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Transient receptor potential vanilloid 2 mediates the inhibitory effect of far-infrared irradiation on adipogenic differentiation of tonsil-derived mesenchymal stem cells.

Stem Cell Res 2021 Mar 17;53:102291. Epub 2021 Mar 17.

Department of Molecular Medicine, College of Medicine, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Republic of Korea; Graduate Program in System Health Science and Engineering, Ewha Womans University, 25 Magokdong-ro-2-gil, Gangseo-gu, Seoul 07804, Republic of Korea. Electronic address:

Aims: Far-infrared (FIR) irradiation inhibits adipogenic differentiation of tonsil-derived mesenchymal stem cells (TMSCs) by activating Ca-dependent protein phosphatase 2B (PP2B), but it stimulates osteogenic differentiation in a PP2B-independent pathway. We investigated the potential involvement of transient receptor potential vanilloid (TRPV) channels, a well-known Ca-permeable channel, in the effects of FIR irradiation on adipogenic or osteogenic differentiation of TMSCs.

Methods: TMSCs, in the absence or presence of activators or inhibitors, were exposed to FIR irradiation followed by adipogenic or osteogenic differentiation, which was assessed using Oil red O or Alizarin red S staining, respectively. Read More

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Population pharmacokinetic modeling and simulation to support qualification of pyridoxic acid as endogenous biomarker of OAT1/3 renal transporters.

CPT Pharmacometrics Syst Pharmacol 2021 Mar 11. Epub 2021 Mar 11.

Centre for Applied Pharmacokinetic Research, School of Health Sciences, The University of Manchester, Manchester, UK.

Renal clearance of many drugs is mediated by renal organic anion transporters OAT1/3 and inhibition of these transporters may lead to drug-drug interactions (DDIs). Pyridoxic acid (PDA) and homovanillic acid (HVA) were indicated as potential biomarkers of OAT1/3. The objective of this study was to develop a population pharmacokinetic model for PDA and HVA to support biomarker qualification. Read More

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Novel Pannexin-1-Coupled Signaling Cascade Involved in the Control of Endothelial Cell Function and NO-Dependent Relaxation.

Oxid Med Cell Longev 2021 20;2021:2678134. Epub 2021 Feb 20.

Departamento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile.

Deletion of pannexin-1 (Panx-1) leads not only to a reduction in endothelium-derived hyperpolarization but also to an increase in NO-mediated vasodilation. Therefore, we evaluated the participation of Panx-1-formed channels in the control of membrane potential and [Ca] of endothelial cells. Changes in NO-mediated vasodilation, membrane potential, superoxide anion (O) formation, and endothelial cell [Ca] were analyzed in rat isolated mesenteric arterial beds and primary cultures of mesenteric endothelial cells. Read More

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February 2021

Clinical Investigation of Metabolic and Renal Clearance Pathways Contributing to the Elimination of Fevipiprant Using Probenecid as Perpetrator.

Drug Metab Dispos 2021 May 25;49(5):389-394. Epub 2021 Feb 25.

Novartis Institutes for Biomedical Research, Basel, Switzerland (H.M.W., T.L., G.R., and B.P.); Novartis Institutes for Biomedical Research, Cambridge, Massachusetts (M.C.); Novartis Institutes for Biomedical Research, East Hanover, New Jersey (S.K. and B.S.); and Novartis Healthcare Pvt. Ltd., Hyderabad, India (J.V.).

Fevipiprant, an oral, nonsteroidal, highly selective, reversible, and competitive prostaglandin D receptor 2 antagonist, is eliminated by glucuronidation and by direct renal excretion predominantly via organic anion transporter (OAT) 3. This study aimed to assess the effect of simultaneous UDP-glucuronosyltransferase (UGT) and OAT3 inhibition by probenecid on the pharmacokinetics of fevipiprant and its acyl glucuronide (AG) metabolite to support the dosing recommendation of fevipiprant in the presence of drugs inhibiting these pathways; however, phase III clinical trial results did not support its submission. This was a single-center, open-label, single-sequence, two-period crossover study in healthy subjects. Read More

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Effects of Probenecid on Hepatic and Renal Disposition of Hexadecanedioate, an Endogenous Substrate of Organic Anion Transporting Polypeptide 1B in Rats.

J Pharm Sci 2021 05 17;110(5):2274-2284. Epub 2021 Feb 17.

Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. Electronic address:

The aim of the present study was to investigate changes in plasma concentrations and tissue distribution of endogenous substrates of organic anion transporting polypeptide (OATP) 1B, hexadecanedioate (HDA), octadecanedioate (ODA), tetradecanedioate (TDA), and coproporphyrin-III, induced by its weak inhibitor, probenecid (PBD), in rats. PBD increased the plasma concentrations of these four compounds regardless of bile duct cannulation, whereas liver-to-plasma (K) and kidney-to-plasma concentration ratios of HDA and TDA were reduced. Similar effects of PBD on plasma concentrations and K of HDA, ODA, and TDA were observed in kidney-ligated rats, suggesting a minor contribution of renal disposition to the overall distribution of these three compounds. Read More

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

Pharmaceutics 2021 Jan 9;13(1). Epub 2021 Jan 9.

College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea.

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 K of 26. Read More

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January 2021

Uric acid inhibits HMGB1-TLR4-NF-κB signaling to alleviate oxygen-glucose deprivation/reoxygenation injury of microglia.

Biochem Biophys Res Commun 2021 02 9;540:22-28. Epub 2021 Jan 9.

Department of Endocrinology, Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China; Xiamen Key Laboratory of Translational Medicine for Nucleic Acid Metabolism and Regulation, Xiamen, Fujian, China. Electronic address:

Mounting evidence has implicated inflammation in ischemia-reperfusion injury following acute ischemic stroke (AIS). Microglia remain the primary initiator and participant of brain inflammation. Emerging evidence has indicated that uric acid has promise for the treatment of AIS, but its explicit mechanisms remain elusive. Read More

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February 2021

Probenecid Increases the Concentration of 7-Chlorokynurenic Acid Derived from the Prodrug 4-Chlorokynurenine within the Prefrontal Cortex.

Mol Pharm 2021 01 13;18(1):113-123. Epub 2020 Dec 13.

Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool L69 3GL, U.K.

Recent advances in the understanding of depression have led to increasing interest in ketamine and the role that -methyl-d-aspartate (NMDA) receptor inhibition plays in depression. l-4-Chlorokynurenine (4-Cl-KYN, AV-101), a prodrug, has shown promise as an antidepressant in preclinical studies, but this promise has not been realized in recent clinical trials. We sought to determine if transporters in the CNS could be playing a role in this clinical response. Read More

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January 2021

The search for brain-permeant NKCC1 inhibitors for the treatment of seizures: Pharmacokinetic-pharmacodynamic modelling of NKCC1 inhibition by azosemide, torasemide, and bumetanide in mouse brain.

Epilepsy Behav 2021 01 2;114(Pt A):107616. Epub 2020 Dec 2.

Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, Germany; Center for Systems Neuroscience, Hannover, Germany. Electronic address:

Because of its potent inhibitory effect on the Na-K-2Cl symporter isotype 1 (NKCC1) in brain neurons, bumetanide has been tested with varying results for treatment of seizures that potentially evolve as a consequence of abnormal NKCC1 activity. However, because of its physicochemical properties, bumetanide only poorly penetrates into the brain. We previously demonstrated that NKCC1 can be also inhibited by azosemide and torasemide, which lack the carboxyl group of bumetanide and thus should be better brain-permeable. Read More

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January 2021

Activation of pannexin-1 mediates triglyceride-induced macrophage cell death.

BMB Rep 2020 Nov;53(11):588-593

Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Korea.

The accumulation of triglycerides (TGs) in macrophages induces cell death, a risk factor in the pathogenesis of atherosclerosis. We had previously reported that TG-induced macrophage death is triggered by caspase-1 and -2, therefore we investigated the mechanism underlying this phenomenon. We found that potassium efflux is increased in TG-treated THP-1 macrophages and that the inhibition of potassium efflux blocks TG-induced cell death as well as caspase-1 and -2 activation. Read More

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November 2020

Nogo-A/S1PR2 Signaling Pathway Inactivation Decreases Microvascular Damage and Enhances Microvascular Regeneration in PDMCI Mice.

Neuroscience 2020 11 9;449:21-34. Epub 2020 Oct 9.

Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510120, China. Electronic address:

The incidence of mild cognitive impairment in Parkinson's disease (PDMCI) is as high as 18-55%. However, the pathological mechanism of PDMCI is not yet clear. Our previous research showed that microvascular pathology and chronic cerebral hypoperfusion participated in the occurrence and development of PDMCI. Read More

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November 2020

[I]MIBG exports via MRP transporters and inhibition of the MRP transporters improves accumulation of [I]MIBG in neuroblastoma.

Nucl Med Biol 2020 Nov - Dec;90-91:49-54. Epub 2020 Sep 28.

School of Health Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan; Biomedical Imaging Research Center, University of Fukui, Fukui, Japan.

Introduction: I-labeled m-iodobenzylguanidine ([I]MIBG) has been used to treat neuroblastoma patients, but [I]MIBG may be immediately excreted from the cancer cells by the adenosine triphosphate binding cassette transporters, similar to anticancer drugs. The purpose of this study was to clarify the efflux mechanism of [I]MIBG in neuroblastomas and improve accumulation by inhibition of the transporter in neuroblastomas.

Methods: [I]MIBG was incubated in human embryonic kidney (HEK)293 cells expressing human organic anion transporting polypeptide (OATP)1B1, OATP1B3, OATP2B1, organic anion transporter (OAT)1 and OAT2, organic cation transporter (OCT)1 and OCT2, and sodium taurocholate cotransporting polypeptide, and in vesicles expressing P-glycoprotein (MDR1), multidrug resistance associated protein (MRP)1-4, or breast cancer resistance protein with and without MK-571 and probenecid (MRP inhibitors). Read More

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September 2020

Interaction of Halogenated Tyrosine/Phenylalanine Derivatives with Organic Anion Transporter 1 in the Renal Handling of Tumor Imaging Probes.

J Pharmacol Exp Ther 2020 12 27;375(3):451-462. Epub 2020 Sep 27.

Department of Bio-system Pharmacology, Graduate School of Medicine (C.J., L.W., R.O., M.X., S.O., H.O., Ya.K., Yo.K.) and Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiative (OTRI) (Yo.K.), Osaka University, Osaka, Japan; Department of Oncology Clinical Development, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan (H.T.); School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China (L.W., X.H.); and Department of Collaborative Research for Bio-Molecular Dynamics, Nara Medical University, Nara, Japan (S.N.)

Halogenated tyrosine/phenylalanine derivatives have been developed for use in tumor imaging and targeted alpha therapy. 3-Fluoro--methyl-l-tyrosine (FAMT), targeting amino acid transporter LAT1 (SLC7A5), is a cancer-specific positron emission tomography probe that exhibits high renal accumulation, which is supposed to be mediated by organic anion transporter OAT1 (SLC22A6). In the present study, we investigated the structural requirements of FAMT essential for interaction with OAT1. Read More

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December 2020

Five Novel Non-Sialic Acid-Like Scaffolds Inhibit In Vitro H1N1 and H5N2 Neuraminidase Activity of Influenza a Virus.

Molecules 2020 Sep 16;25(18). Epub 2020 Sep 16.

Laboratorio de Simulaciones Computacionales Moleculares, Facultad de Ciencias Químicas, Benemérita Universidad Autónoma de Puebla, Puebla 72592, Mexico.

Neuraminidase (NA) of influenza viruses enables the virus to access the cell membrane. It degrades the sialic acid contained in extracellular mucin. Later, it is responsible for releasing newly formed virions from the membrane of infected cells. Read More

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September 2020

Influence of Probenecid on the Pharmacokinetics and Pharmacodynamics of Sorafenib.

Pharmaceutics 2020 Aug 20;12(9). Epub 2020 Aug 20.

Department of Medical Oncology, Erasmus MC Cancer Institute, 3015 CE Rotterdam, The Netherlands.

Prior studies have demonstrated an organic anion transporter 6 (OAT6)-mediated accumulation of sorafenib in keratinocytes. The OAT6 inhibitor probenecid decreases sorafenib uptake in skin and might, therefore, decrease sorafenib-induced cutaneous adverse events. Here, the influence of probenecid on sorafenib pharmacokinetics and toxicity was investigated. Read More

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Detection of Weak Organic Anion-Transporting Polypeptide 1B Inhibition by Probenecid with Plasma-Based Coproporphyrin in Humans.

Drug Metab Dispos 2020 10 28;48(10):841-848. Epub 2020 Jul 28.

Departments of Metabolism and Pharmacokinetics (Y.Z., M.S., H.S.) and Bioanalytical Sciences (H.K., J.Z.), Bristol Myers Squibb Company, Princeton, New Jersey; and Departments of Metabolism and Pharmacokinetics (V.K.H., T.T.M.), Biocon Bristol Myers Squibb R&D Centre (BBRC), Syngene International Ltd., Biocon Park, Bommasandra IV Phase, Bangalore, India

Probenecid (PROB) is a clinical probe inhibitor of renal organic anion transporter (OAT) 1 and OAT3 that inhibits in vitro activity of hepatic drug transporters OATP1B1 and OATP1B3. It was hypothesized that PROB could potentially affect the disposition of OATP1B drug substrates. The plasma levels of the OATP1B endogenous biomarker candidates, including coproporphyrin I (CPI), CPIII, hexadecanedioate (HDA), and tetradecanedioate (TDA), were examined in 14 healthy subjects treated with PROB. Read More

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October 2020

Inhibition of ABCC6 Transporter Modifies Cytoskeleton and Reduces Motility of HepG2 Cells via Purinergic Pathway.

Cells 2020 06 5;9(6). Epub 2020 Jun 5.

Department of Sciences, University of Basilicata, viale Ateneo Lucano 10, 85100 Potenza, Italy.

ABCC6, belonging to sub-family C of ATP-binding cassette transporter, is an ATP-dependent transporter mainly present in the basolateral plasma membrane of hepatic and kidney cells. Although the substrates transported are still uncertain, ABCC6 has been shown to promote ATP release. The extracellular ATP and its derivatives di- and mono-nucleotides and adenosine by acting on specific receptors activate the so-called purinergic pathway, which in turn controls relevant cellular functions such as cell immunity, inflammation, and cancer. Read More

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Absorption and Disposition of Coproporphyrin I (CPI) in Cynomolgus Monkeys and Mice: Pharmacokinetic Evidence to Support the Use of CPI to Inform the Potential for Organic Anion-Transporting Polypeptide Inhibition.

Drug Metab Dispos 2020 08 1;48(8):724-734. Epub 2020 Jun 1.

Departments of Metabolism and Pharmacokinetics (X.G., L.W., J.G., R.M.F., Y.L., M.S., H.S.) and Radiochemistry (Y.T., Y.H.), Bristol Myers Squibb Company, Princeton, New Jersey

Despite a recent expansion in the recognition of the potential utility of coproporphyrin (CP) as an endogenous biomarker of organic anion-transporting polypeptide (OATP) 1B activity, there have been few detailed studies of CP's pharmacokinetic behavior and an overall poor understanding of its pharmacokinetic fate from tissues and excretion. Here, we describe the pharmacokinetics of octadeuterium-labeled coproporphyrin I (CPI-d8) in cynomolgus monkeys following oral and intravenous administration. CPI-d8 has a half-life and bioavailability of 7. Read More

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Acute Pannexin 1 Blockade Mitigates Early Synaptic Plasticity Defects in a Mouse Model of Alzheimer's Disease.

Front Cell Neurosci 2020 19;14:46. Epub 2020 Mar 19.

Centro de Neurología Traslacional, Facultad de Medicina, Universidad de Valparaíso, Valparaíso, Chile.

Synaptic loss induced by soluble oligomeric forms of the amyloid β peptide (sAβos) is one of the earliest events in Alzheimer's disease (AD) and is thought to be the major cause of the cognitive deficits. These abnormalities rely on defects in synaptic plasticity, a series of events manifested as activity-dependent modifications in synaptic structure and function. It has been reported that pannexin 1 (Panx1), a nonselective channel implicated in cell communication and intracellular signaling, modulates the induction of excitatory synaptic plasticity under physiological contexts and contributes to neuronal death under inflammatory conditions. Read More

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MK-571, a Cysteinyl Leukotriene Receptor 1 Antagonist, Inhibits Hepatitis C Virus Replication.

Antimicrob Agents Chemother 2020 05 21;64(6). Epub 2020 May 21.

Institut Mondor de Recherche Biomédicale (IMRB), INSERM U955, Team "Viruses, Hepatology, Cancers", Hôpital Henri Mondor, Université Paris-Est, Créteil, France

The quinoline MK-571 is the most commonly used inhibitor of multidrug resistance protein-1 (MRP-1) but was originally developed as a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. While studying the modulatory effect of MRP-1 on anti-hepatitis C virus (HCV) direct-acting antiviral (DAA) efficiency, we observed an unexpected anti-HCV effect of compound MK-571 alone. This anti-HCV activity was characterized in Huh7. Read More

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Monocarboxylate Transporters (SLC16): Function, Regulation, and Role in Health and Disease.

Pharmacol Rev 2020 04;72(2):466-485

Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, California (M.A.F.); Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York (R.S.J., V.R.-C., M.E.M.); and Certara Strategic Consulting, Certara USA, Princeton, New Jersey (K.E.F.)

The solute carrier family 16 (SLC16) is comprised of 14 members of the monocarboxylate transporter (MCT) family that play an essential role in the transport of important cell nutrients and for cellular metabolism and pH regulation. MCTs 1-4 have been extensively studied and are involved in the proton-dependent transport of L-lactate, pyruvate, short-chain fatty acids, and monocarboxylate drugs in a wide variety of tissues. MCTs 1 and 4 are overexpressed in a number of cancers, and current investigations have focused on transporter inhibition as a novel therapeutic strategy in cancers. Read More

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Impact of renal impairment and human organic anion transporter inhibition on pharmacokinetics, safety and tolerability of relebactam combined with imipenem and cilastatin.

Br J Clin Pharmacol 2020 05 23;86(5):944-957. Epub 2020 Jan 23.

Merck & Co., Inc., Kenilworth, NJ, USA.

Aims: Two phase 1, open-label studies were conducted to investigate the effect of renal impairment (RI) and organic anion transporter (OAT) inhibition on pharmacokinetics (PK) and safety of relebactam (REL) plus imipenem/cilastatin (IMI).

Methods: Study PN005 evaluated the PK of REL (125 mg) plus IMI (250 mg) in participants with RI vs healthy controls. Study PN019 evaluated the PK of REL (250 mg) and imipenem (500 mg; dosed as IMI) with/without probenecid (1 g; OAT inhibitor) in healthy adults. Read More

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Interaction of Organic Anion Transporter 3-Mediated Uptake of Steviol Acyl Glucuronide, a Major Metabolite of Rebaudioside A, with Selected Drugs.

J Agric Food Chem 2020 Feb 28;68(6):1579-1587. Epub 2020 Jan 28.

College of Pharmaceutical Sciences , Soochow University , Suzhou 215006 , China.

Organic anion transporter 3 (OAT3) plays a critical role in the renal excretion of many xenobiotics. Because steviol acyl glucuronide (SVAG), an OAT3 substrate, is the major circulating metabolite after oral ingestion of steviol glycosides and is excreted into the urine, inhibition of OAT3 activity may alter pharmacokinetic profiles of SVAG. The present study showed that drugs such as probenecid and glimepiride displayed potent inhibition toward the OAT3-mediated SVAG transport, with IC values of 4. Read More

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February 2020

Hydralazine improves ischemia-induced neovasculogenesis via xanthine-oxidase inhibition in chronic renal insufficiency.

Pharmacol Res 2020 01 1;151:104509. Epub 2019 Nov 1.

Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan, ROC; Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC; Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC. Electronic address:

Oxidative stress is related to the progression of renal diseases and modulation of oxidative stress can lead to a reduction in vascular events in patients with chronic renal insufficiency (CRI). Indoxyl sulfate (IS) and xanthine oxidase (XO) are related to impaired neovasculogenesis in CRI. Hydralazine is suggested for blood pressure control in CRI. Read More

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January 2020

Cilastatin protects against imipenem-induced nephrotoxicity inhibition of renal organic anion transporters (OATs).

Acta Pharm Sin B 2019 Sep 18;9(5):986-996. Epub 2019 Feb 18.

Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China.

Imipenem is a carbapenem antibiotic. However, Imipenem could not be marketed owing to its instability and nephrotoxicity until cilastatin, an inhibitor of renal dehydropeptidase-I (DHP-I), was developed. In present study, the potential roles of renal organic anion transporters (OATs) in alleviating the nephrotoxicity of imipenem by cilastatin were investigated and in rabbits. Read More

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September 2019

Enhancing the copy number of Ldrab6 gene in Leishmania donovani parasites mediates drug resistance through drug-thiol conjugate dependent multidrug resistance protein A (MRPA).

Acta Trop 2019 Nov 3;199:105158. Epub 2019 Sep 3.

Biochemistry Division, CSIR-Central Drug Research Institute, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address:

Visceral leishmaniasis (VL) is a neglected tropical disease caused by protozoan Leishmania donovani parasite which may be fatal if left untreated. While drug-sensitive parasites are able to live and multiply within the host macrophages, they develop resistance to drugs used against them for survival and multiplication in the infected patients undergoing routine treatment. Development of new agents devoid of such drug resistance potential is achievable by identifying new drug targets in the parasite. Read More

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November 2019

Inhibitory Effect of Probenecid on Osteoclast Formation via JNK, ROS and COX-2.

Biomol Ther (Seoul) 2020 Jan;28(1):104-109

Department of Pharmacology and Toxicology, School of Dentistry, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

Probenecid is a representative drug used in the treatment of gout. A recent study showed that probenecid effectively inhibits oxidative stress in neural cells. In the present study, we investigated whether probenecid can affect osteoclast formation through the inhibition of reactive oxygen species (ROS) formation in RAW264. Read More

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January 2020