Regulation of Solute Carriers OCT2 and OAT1/3 in the Kidney: A Phylogenetic, Ontogenetic and Cell Dynamic Perspective

2021 ◽  
Author(s):  
Carla Pou Casellas ◽  
Katja Jansen ◽  
Maarten B Rookmaaker ◽  
Hans Clevers ◽  
Marianne C. Verhaar ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Organic Anion ◽  
Organic Cation Transporter ◽  
The Body ◽  
In Vitro Test ◽  
Solute Carriers ◽  
Test Models ◽  
Progression Of Kidney Disease ◽  
Dynamic Perspective

Over the course of more than 500 million years, the kidneys have undergone a remarkable evolution from primitive nephric tubes to intricate filtration-reabsorption systems that maintain homeostasis and remove metabolic end products from the body. The evolutionarily conserved solute carriers Organic Cation Transporter 2 (OCT2), and Organic Anion Transporters 1 and 3 (OAT1/3) coordinate the active secretion of a broad range of endogenous and exogenous substances, many of which accumulate in the blood of patients with kidney failure despite dialysis. Harnessing OCT2 and OAT1/3 through functional preservation or regeneration could alleviate the progression of kidney disease. Additionally, it would improve current in vitro test models that lose their expression in culture. With this review, we explore OCT2 and OAT1/3 regulation using different perspectives: phylogenetic, ontogenetic and cell dynamic. Our aim is to identify possible molecular targets to both help prevent or compensate for the loss of transport activity in patients with kidney disease, and to enable endogenous OCT2 and OAT1/3 induction in vitro in order to develop better models for drug development.

scholarly journals EFEK EKSTRAK ETANOL BIJI LABU KUNING (CUCURBITA MOSCHATA DUCHESNE) SEBAGAI ANTELMINTIK PADA CACING GELANG (ASCARIDIA GALLI)

2020 ◽  
Vol 7 (1) ◽  
pp. 11-18
Author(s):  
Noni Zakiah ◽  
Vonna Aulianshah ◽  
T. Maulana Hidayatullah ◽  
Faridah Hanum
Keyword(s):  
Ethanol Extract ◽  
Positive Control ◽  
The Body ◽  
Whole Body ◽  
In Vitro Test ◽  
Cucurbita Moschata ◽  
Ascaridia Galli ◽  
Group I ◽  
Pumpkin Seeds

Kegunaan labu kuning di Indonesia masih sebatas daging buah yang dapat diolah menjadi panganan seperti kue basah, kolak dan sayur berkuah. Secara empiris, biji labu kuning telah digunakan untuk mengatasi cacingan. Penelitian ini dilakukan untuk mengetahui mortalitas cacing gelang (Ascaridia galli) dalam ekstrak etanol biji labu kuning (Cucurbita moschata Duchesne). Penelitian ini menggunakan 25 ekor Ascaridia galli yang dibagi menjadi 5 kelompok, kelompok I kontrol negatif menggunakan larutan NaCl fisiologis, kelompok II kontrol positif menggunakan larutan pirantel pamoat 0,5 %, kelompok III, IV dan V berturut-turut menggunakan 25 mg/ml, 50 mg/ml dan 100 mg/ml ekstrak etanol biji labu kuning. Parameter penelitian ini ditentukan dengan melihat persentase nilai skor pasca inkubasi 12 jam, 24 jam, dan 36 jam. Skor 3 diberikan apabila seluruh tubuh Ascaridia galli bergerak, skor 2 diberikan jika hanya sebagian tubuh Ascaridia galli bergerak, skor 1 jika Ascaridia galli diam tetapi masih hidup, dan skor 0 apabila Ascaridia galli mati. Hasil uji in vitro dengan perlakuan 25 mg/ml ekstrak etanol biji labu kuning menyebabkan kematian 3 ekor Ascaridia galli  atau 60% pasca inkubasi 36 jam, sedangkan ekstrak etanol biji labu kuning dengan perlakuan 50 mg/ml, 100 mg/ml dan kelompok kontrol positif mengakibatkan kematian 4 ekor Ascaridia galli atau 80% pasca inkubasi 36 jam. Dari hasil penelitian disimpulkan bahwa ekstrak etanol biji labu kuning (Cucurbita moschata Duchesne) dosis 25 mg/ml, 50 mg/ml, dan 100 mg/ml secara in vitro dalam waktu 36 jam mampu mengakibatkan mortalitas Ascaridia galli. The use of yellow pumpkin in Indonesia is still limited to fruit meat that can be processed into snacks such as soggy cakes, porridge and vegetable soup. This research was conducted to determine the mortality of Ascaridia galli in ethanol extract of yellow pumpkin seeds (Cucurbita moschata Duchesne). This study used 25 Ascaridia galli which were divided into 5 groups, group I was negative control using physiological NaCl solution, group II was positive control using 0.5% pirantel pamoate solution, group III, IV and V respectively used 25 mg / ml, 50 mg/ml and 100 mg/ml ethanol extract of yellow pumpkin seeds. The parameters of this study were determined by looking at the percentage of post-incubation scores 12 hours, 24 hours, and 36 hours. A score of 3 is given if the whole body of Ascaridia galli moves, a score of 2 is given if only part of the body of Ascaridia galli moves, a score of 1 if Ascaridia galli is still but still alive, and a score of 0 if Ascaridia galli dies. In vitro test results with 25 mg/ml ethanol extract of pumpkin seeds caused 3 deaths of Ascaridia galli or 60% after incubation for 36 hours, while ethanol extract of yellow pumpkin seeds treated with 50 mg / ml, 100 mg/ml and positive control group resulting in the death of 4 Ascaridia galli or 80% after 36 hours incubation. From the results of the study concluded that the ethanol extract of yellow pumpkin seeds (Cucurbita moschata Duchesne) doses of 25 mg / ml, 50 mg / ml, and 100 mg / ml in vitro within 36 hours can lead to Ascaridia galli mortality.

Effect of Acid Stress on the Behavior of Soil Nematodes

2014 ◽  
Vol 522-524 ◽  
pp. 341-345
Author(s):  
Dan Dan Liu ◽  
Yan Ling Cui ◽  
Chang Feng Liu ◽  
Xin Lin Gao ◽  
Yin Yao Xia
Keyword(s):  
Body Fluid ◽  
Acid Stress ◽  
Optical Microscope ◽  
The Body ◽  
Individual Development ◽  
Movement Behavior ◽  
Soil Nematode ◽  
In Vitro Test ◽  
Stylet Length

In vitro test was used to determine the effect of acid stress on soil nematode (Meloidogyne incognita) J2 survival, behavior, individual development and fluid extravasations. The effects of acid stress on J2 survival is C2H2O4>C6H8O7>C4H6O5. Inhibition on J2 movement behavior increased with time prolonged. Effect on nematode body length, stylet length, tail transparent area length, body fluid extravasations: C2H2O4>C6H8O7>C4H6O5. At high magnification optical microscope can be clearly observed symptoms of poisoning J2. Compared with the control, acid inhibited the nematode survival, movement and individual development, promote the body fluid extravasations, destroyed the normal physiological metabolism of nematodes, even lead to death.

scholarly journals Antitubercular Agent Delamanid and Metabolites as Substrates and Inhibitors of ABC and Solute Carrier Transporters

2016 ◽  
Vol 60 (6) ◽  
pp. 3497-3508 ◽  
Author(s):  
Hiroyuki Sasabe ◽  
Yoshihiko Shimokawa ◽  
Masakazu Shibata ◽  
Kenta Hashizume ◽  
Yusuke Hamasako ◽  
...  
Keyword(s):  
Abc Transporters ◽  
Organic Anion ◽  
Organic Cation Transporter ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Cancer Resistance ◽  
Slc Transporters ◽  
Solute Carrier ◽  
Multiple Drugs

Delamanid (Deltyba, OPC-67683) is the first approved drug in a novel class of nitro-dihydro-imidazooxazoles developed for the treatment of multidrug-resistant tuberculosis. Patients with tuberculosis require treatment with multiple drugs, several of which have known drug-drug interactions. Transporters regulate drug absorption, distribution, and excretion; therefore, the inhibition of transport by one agent may alter the pharmacokinetics of another, leading to unexpected adverse events. Therefore, it is important to understand how delamanid affects transport activity. In the present study, the potencies of delamanid and its main metabolites as the substrates and inhibitors of various transporters were evaluatedin vitro. Delamanid was not transported by the efflux ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp; MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2), solute carrier (SLC) transporters, organic anion-transporting polypeptides, or organic cation transporter 1. Similarly, metabolite 1 (M1) was not a substrate for any of these transporters except P-gp. Delamanid showed no inhibitory effect on ABC transporters MDR1, BCRP, and bile salt export pump (BSEP; ABCB11), SLC transporters, or organic anion transporters. M1 and M2 inhibited P-gp- and BCRP-mediated transport but did so only at the 50% inhibitory concentrations (M1, 4.65 and 5.71 μmol/liter, respectively; M2, 7.80 and 6.02 μmol/liter, respectively), well above the corresponding maximum concentration in plasma values observed following the administration of multiple doses in clinical trials. M3 and M4 did not affect the activities of any of the transporters tested. Thesein vitrodata suggest that delamanid is unlikely to have clinically relevant interactions with drugs for which absorption and disposition are mediated by this group of transporters.

scholarly journals Allergen Extraction: Factors Influencing Immunogenicity and Sensitivity of Immunoassays

2021 ◽  
Author(s):  
João Ricardo Almeida Soares ◽  
Airton Pereira e SIlva ◽  
Isabelle Guimarães ◽  
Ana Luisa Oliveira ◽  
Claudia Regina Faccini ◽  
...  
Keyword(s):  
Social Impact ◽  
Protein Extraction ◽  
Protein Profile ◽  
Physiological Saline ◽  
Extraction Methods ◽  
The Body ◽  
Mouse Strains ◽  
In Vitro Test

Because of the high social impact of Food allergy, it is of great importance to correctly diagnose this disease using reliable tests. Knowledge of the allergenicity properties of proteins, how they react in the body and in diagnostic tests is necessary to adequately assess the potential immunogenicity of both natural foods and those produced through biotechnological processes. Thus, our aim was to analyze the factors that influence the protein extraction of foods in terms of, immunogenicity and immunoassays sensitivity. Peanut proteins were extracted using four distinct extraction buffers (physiological saline, tris buffer, borate buffer with and without β-mercaptoethanol), the protein concentration was determined by the Lowry method and polyacrylamide electrophoresis (SDS-PAGE) was used to compare the protein profile of each extract. The immunogenicity of each extract was verified by sensitizing two mouse strains (Balb/c and C57/BL6) with solution containing 100μg of the extracted proteins and determined by ELISA. Results show that extraction with the distinct buffers resulted in protein solutions with different yields and profiles. The immunogenicity of the different extracts also demonstrated distinct patterns that varied depending on the extraction methods, mouse strain and in-vitro test. Immunoreactivity varied in accordance to the protein extract used to coat the microtitration plates. In conclusion, the protein profile in the extracts is critically influenced by the salt composition and pH of the extraction buffers, this in turn influences both in vivo immunogenicity and in vitro immunoreactivity.

RFID Pharmaceutical Tracking: From Manufacturer Through In Vivo Drug Delivery

2009 ◽  
Vol 4 (1) ◽  
Author(s):  
Erick Jones ◽  
Marcia Henry ◽  
David Cochran ◽  
Tara Frailey
Keyword(s):  
Radio Frequency Identification ◽  
Information Needs ◽  
Tracking System ◽  
Disease Diagnosis ◽  
The Body ◽  
Test Method ◽  
In Vitro Test ◽  
Supply Chain System ◽  
Pharmaceutical Supply Chain

Advances in medical technology rely heavily on the collection and analysis of measured data to facilitate patient diagnosis and business decisions. The healthcare industry, particularly pharmaceuticals and diagnostic processes, has an ongoing need to improve item tracking and data collection to improve the quality of care while reducing cost. The remote, non-invasive characteristics of radio frequency identification (RFID) can facilitate the information needs of healthcare without imposing additional burden onto the patient or the staff. Properly deployed RFID enabled devices can provide convenient and accurate data for disease diagnosis, evaluation of prescription noncompliance, and identification of medication dosage errors. This paper describes an overview of the concept of an all-encompassing RFID pharmaceutical tracking system that begins with compliance documentation from the drug manufacturer and continues through the confirmation of patient compliance by capsule extraction from the bottle into a pill case and ultimately ingested or inserted into the body. This system also facilitates compliance with Food and Drug Administration proposed e-pedigree requirements and provides data for healthcare decision making. An introduction to healthcare trends is provided in order to communicate the need for such a biocompatible RFID pharmaceutical tracking system. Also presented in this paper is the overall scope of research and in vitro test method to develop biocompatible RFID tag components for use in a “pharmaceutical supply chain system” beginning with the manufacturer, continuing through distribution, and ending at the point of interest within the patient’s body.

Critical Evaluation of an in Vitro Model for Evaluation of Platelet Reactivity of Biomaterials

1987 ◽  
Vol 110 ◽  
Author(s):  
Raymond Connolly ◽  
Norman Shoenfeld ◽  
Karen Ramberg ◽  
Allan D. Callow
Keyword(s):  
In Vitro Model ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Critical Evaluation ◽  
The Body ◽  
Test Material ◽  
In Vitro Test ◽  
Vitro Model

AbstractAn in vitro model for measuring platelet reactivity to a variety of biomaterial candidates for vascular grafts is described. A model consisting of a standard area of test material exposed to freshly labeled In platelets in plasma was evaluated. The platelets were isolated from ACD anticoagulated blood and resuspended in ACD plasma. It has been previously demonstrated that platelets so treated circulate in the body and will deposit on biomaterials exposed to the blood in vivo. The in vitro test consisted of an incubation of the platelets and materials at 37°C for one hour. At the end of the incubation, the platelet rich plasma was removed and the materials washed and removed for gamma counting. Platelet reactivity was normalized as a percentage of the counts on the material to counts in an aliquot of the platelet-plasma incubation media. The maximum uptake of platelets occurred within one hour. Platelets from three species, human, baboon, and dog were tested. Platelet uptake by Dacron and PTFE were in the range of 30–40% and 1–5% respectively. This is in accord with the known reactivity of these two vascular graft materials in vivo.A second series of studies were conducted with physically and pharmacologically inactivated platelets and inert particles. Those studies suggest that the initial results do not represent a biologic event but may reflect the porosity of the materials. This emphasizes the necessity of adequately defining an in vitro model against known in vivo activity.

scholarly journals Study on the Mechanism of the Blood-Glucose-Lowering Effect of Collagen Peptides from Sturgeon By-Products

Marine Drugs ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. 584
Author(s):  
Yukiho Sasaoka ◽  
Taichi Takagi ◽  
Shunta Michiba ◽  
Yohei Yamamoto ◽  
Yuya Kumagai ◽  
...  
Keyword(s):  
Small Intestine ◽  
Blood Glucose ◽  
Inhibitory Effect ◽  
The Body ◽  
In Vitro Test ◽  
Intravenous Glucose ◽  
Collagen Peptides ◽  
Dpp Iv ◽  
By Products

In a previous study, we found that the collagen peptides prepared from the by-products of Bester sturgeon had an inhibitory effect on elevated blood glucose levels in a glucose tolerance test with ICR mice. In the present study, we examine the mechanism of the effect of sturgeon collagen peptides (SCPs) in detail. When glucose was orally administered to mice along with the SCPs, it was found that the glucose remained in the stomach for a longer time. In the above tests, the amount of glucose excreted in the feces of mice also increased. On the contrary, it was revealed that the SCPs have a dipeptidyl-peptidase-IV (DPP-IV) inhibitory ability in an in vitro test. In subsequent oral and intravenous glucose administration tests, glucagon-like peptide-1 (GLP-1) and insulin levels in the blood of mice were maintained at high levels. These results suggested the following three mechanisms: SCPs slow the rate of transportation of glucose from the stomach into the small intestine, resulting in delayed glucose absorption; SCPs suppress the absorption of glucose in the small intestine and excrete it from the body; SCPs inhibit DPP-IV in the blood and maintain a high GLP-1 level in blood, which in turn stimulates insulin secretion.

Movement of Hydroxyurea Across Cell Membranes Is Mediated by Specific Solute Carrier (SLC) Transporters.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2575-2575
Author(s):  
Aisha L. Walker ◽  
Ryan M Franke ◽  
Alex Sparreboom ◽  
Russell E. Ware
Keyword(s):  
Vector Control ◽  
Cellular Uptake ◽  
Organic Cation ◽  
Organic Anion ◽  
Fold Increase ◽  
The Body ◽  
Transcellular Transport ◽  
Slc Transporters ◽  
Solute Carrier

Abstract Abstract 2575 Poster Board II-552 Background: Hydroxyurea is the only FDA-approved drug for the treatment of sickle cell anemia (SCA) in adults. Hydroxyurea increases fetal hemoglobin, decreases hospitalizations and painful events, and reduces mortality. With an oral bioavailability of > 90%, hydroxyurea is rapidly absorbed and distributed throughout the body. Though hydroxyurea has proven to be effective in treating SCA, there is considerable inter-patient variability observed in the pharmacokinetics and pharmacodynamics of hydroxyurea. Currently, mechanisms involved in the absorption, distribution, and elimination of hydroxyurea remain unclear. Recently, key transmembrane proteins have been identified as drug transporters due to their ability to move a variety of xenobiotic substances across cell membranes. Drug transporters are widely distributed throughout the body, and most are specific to certain substrates. Solute carrier (SLC) transporters in particular have been to shown to significantly impact drug pharmacokinetics by influencing the absorption, distribution, and elimination of specific drugs. The present study was designed to identify SLC transporters that may influence the absorption, distribution, and/or elimination of hydroxyurea in patients with SCA. Methods: In vitro studies using an equilibrium dialysis plate were performed to determine the amount of hydroxyurea that binds to human serum proteins. Transporter-mediated cellular uptake of hydroxyurea was determined in vitro by measuring [14C]-hydroxyurea accumulation in HEK293 cells and oocytes that overexpress organic anion transporters (OAT1-3), organic cation transporters (OCT1-3), organic cation/carnitine transporters (OCTN1-2), organic anion transporting polypeptides (OATP1A2/OATP1B1/OATP1B3), or vector control. LLC-PK1 cells that overexpress urea transporters A or B (UTA/UTB) were used to determine UTA/UTB mediated transcellular transport of hydroxyurea in transwell plates. The transport of [14C]-hydroxyurea from apical to basal or from basal to apical compartments was measured for the UTA/UTB overexpressing cells and compared to vector control. UTA and UTB mRNA expression was measured by real-time PCR of cDNA obtained from human tissue samples. Results: Protein binding assays showed that >76% of [14C]-hydroxyurea remained unbound to proteins in human serum containing hydroxyurea at concentrations ranging from 1.5μM to 500μM. The fraction of unbound hydroxyurea was similar using serum obtained from pediatric patients with SCA. In uptake studies, [14C]-hydroxyurea was a potent substrate for OATP1B3 with an approximately 2-fold increase in drug accumulation compared to control (p<0.001). In contrast, hydroxyurea was found to be a weak substrate for OCTN1, OCTN2, OATP1A2, and OATP1B1 with only a 1.3-fold increase in drug accumulation compared to control (p<0.04). Transcellular transport of hydroxyurea was increased 3- and 2-fold by UTA and UTB, respectively, compared to vector control demonstrating hydroxyurea to be a potent substrate for these transporters as well (p<0.02). When the urea transporter inhibitor dimethylurea was added, hydroxyurea transport by UTA and UTB-expressing cells was decreased to levels observed with the vector control. In real-time PCR assays, kidney, muscle, and small intestine were among human tissues with high expression of UTA mRNA, while prostate, brain, and bone marrow had high levels of UTB mRNA expression. Conclusion: Cellular uptake of hydroxyurea is mediated by active transport via specific SLC transporters OATP1B3, UTA and UTB, which are expressed in liver, kidney, brain, intestine, and blood cells. Studies to further characterize hydroxyurea transporters should improve our understanding of the pharmacokinetic and pharmacodynamic profiles of hydroxyurea used in clinical practice for patients with SCA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Islatravir Is Not Expected to Be a Victim or Perpetrator of Drug-Drug Interactions via Major Drug-Metabolizing Enzymes or Transporters

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1566
Author(s):  
Kelly Bleasby ◽  
Robert Houle ◽  
Michael Hafey ◽  
Meihong Lin ◽  
Jingjing Guo ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Organic Anion ◽  
Organic Cation Transporter ◽  
Organic Anion Transporter ◽  
Uridine Diphosphate ◽  
Cancer Resistance ◽  
Treatment And Prevention ◽  
Anion Transporter

Islatravir (MK-8591) is a nucleoside reverse transcriptase translocation inhibitor in development for the treatment and prevention of HIV-1. The potential for islatravir to interact with commonly co-prescribed medications was studied in vitro. Elimination of islatravir is expected to be balanced between adenosine deaminase–mediated metabolism and renal excretion. Islatravir did not inhibit uridine diphosphate glucuronosyltransferase 1A1 or cytochrome p450 (CYP) enzymes CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4, nor did it induce CYP1A2, 2B6, or 3A4. Islatravir did not inhibit hepatic transporters organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter (OCT) 1, bile salt export pump (BSEP), multidrug resistance-associated protein (MRP) 2, MRP3, or MRP4. Islatravir was neither a substrate nor a significant inhibitor of renal transporters organic anion transporter (OAT) 1, OAT3, OCT2, multidrug and toxin extrusion protein (MATE) 1, or MATE2K. Islatravir did not significantly inhibit P-glycoprotein and breast cancer resistance protein (BCRP); however, it was a substrate of BCRP, which is not expected to be of clinical significance. These findings suggest islatravir is unlikely to be the victim or perpetrator of drug-drug interactions with commonly co-prescribed medications, including statins, diuretics, anti-diabetic drugs, proton pump inhibitors, anticoagulants, benzodiazepines, and selective serotonin reuptake inhibitors.

scholarly journals Calcium Signaling Mediates Cell Death and Crosstalk with Autophagy in Kidney Disease

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3204
Author(s):  
Bo Ning ◽  
Chuanzhi Guo ◽  
Anqi Kong ◽  
Kongdong Li ◽  
Yimin Xie ◽  
...  
Keyword(s):  
Cell Death ◽  
Kidney Disease ◽  
Autosomal Dominant ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
The Body ◽  
Polycystic Kidney ◽  
Progression Of Kidney Disease ◽  
Autosomal Dominant Polycystic Kidney

The kidney is an important organ for the maintenance of Ca2+ homeostasis in the body. However, disruption of Ca2+ homeostasis will cause a series of kidney diseases, such as acute kidney injury (AKI), chronic kidney disease (CKD), renal ischemia/reperfusion (I/R) injury, autosomal dominant polycystic kidney disease (ADPKD), podocytopathy, and diabetic nephropathy. During the progression of kidney disease, Ca2+ signaling plays key roles in various cell activities such as necrosis, apoptosis, eryptosis and autophagy. Importantly, there are complex Ca2+ flux networks between the endoplasmic reticulum (ER), mitochondria and lysosomes which regulate intracellular Ca2+ signaling in renal cells and contribute to kidney disease. In addition, Ca2+ signaling also links the crosstalk between various cell deaths and autophagy under the stress of heavy metals or high glucose. In this regard, we present a review of Ca2+ signaling in cell death and crosstalk with autophagy and its potential as a therapeutic target for the development of new and efficient drugs against kidney diseases.

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