Background: Organic anion transporter 1 (OAT1) and OAT3 have an overlapping spectrum of substrates such that one can exert a compensatory effect when the other is dysfunctional. As a result, the knockout of either OAT1 or OAT3 is not reflected in a change in the excretion of organic anionic substrates. To date, only the mOAT1 and mOAT3 individual knockout mouse models have been available.
Methods: In this study, we successfully generated a double-knockout (KO) rat model using CRISPR/Cas9 technology and evaluated its biological properties.
Results: The double-knockout rat model did not expression for rOAT1 or rOAT3 in the kidneys. Consistently, the renal excretion of -aminohippuric acid (PAH), the classical substrate of OAT1/OAT3, was substantially decreased in the double-knockout rats. The relative level of was up-regulated in KO rats. No renal pathological phenotype was evident. The renal elimination of the organic anionic drug furosemide was nearly abolished in the knockout rats, but elimination of the organic cationic drug metformin was hardly affected.
Conclusions: These results demonstrate that this rat model is a useful tool for investigating the functions of OAT1/OAT3 in metabolic diseases, drug metabolism and pharmacokinetics, and OATs-mediated drug interactions.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697873 | PMC |
| http://dx.doi.org/10.3390/pharmaceutics14112307 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Establishment of Rat Models Mimicking Gender-affirming Hormone Therapies.
J Vis Exp
January 2025
Center for Gender-Specific Medicine, Istituto Superiore di Sanità.
Transgender (TG) people are individuals whose gender identity and sex assigned at birth do not match. They often undergo gender-affirming hormone therapy (GAHT), a medical intervention that allows the acquisition of secondary sex characteristics more aligned with their individual gender identity, providing consistent results in the improvement of numerous socio-psychological variables. However, GAHT targets different body systems, and some side effects are recorded, although not yet fully identified and characterized.
View Article and Find Full Text PDFHerbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation.
J Vis Exp
January 2025
Department of Cardiac Surgery, the First Affiliated Hospital of Xinjiang Medical University;
The objective of this study was to investigate the cardioprotective effects of Munziq on abnormal body fluid myocardial ischemia-reperfusion injury (MIRI) and its underlying mechanism.Normal rats and rats with abnormal body fluid (ABF) were pre-treated with Munziq for 21 days. Following this, MIRI models were established.
View Article and Find Full Text PDFNew insight on the acute CCl-induced hepatotoxicity model in rats.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Center of Studies and Research Toxic-Pharmacological, School of Pharmacy, Federal University of Goias, Leste Universitario, 240th Street, Corner of 5th Avenue, Goiania, GO, 74605-170, Brazil.
The CCl-induced hepatotoxicity model is a traditional preclinical assay applied to evaluate potential hepatoprotective compounds. However, several studies have used it with inappropriate dose and exposure time, generating both weak response or irreversible liver injury, as well as lack of representative liver and plasma biomarkers. Therefore, this study aims to determine the best dose and exposure time of CCl in Wistar rats, permitting a proper evaluation of potential hepatoprotective effect.
View Article and Find Full Text PDFFluvoxamine may reverse the decrease in filtering capacity that occurs in acute kidney injury by increasing IL-10 and ACE expressions and preserving AQ-2, AQ-4, CL-5, and ZO-1 expressions.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Division of Nephrology, Faculty of Medicine, Department of Internal Medicine, Suleyman Demirel University, Isparta, Turkey.
The kidneys have a regulatory role in many diseases with their diuresis function and capacity to maintain electrolyte balance. In case of extensive damage, the kidney's filtration capacity is impaired and cannot fulfill its functions. Fluvoxamine (FLV), an antidepressant agent, has antioxidant and anti-inflammatory effects.
View Article and Find Full Text PDFXuefu Zhuyu Decoction improves hyperlipidemia through the MAPK/NF-κB and MAPK/PPARα/CPT-1A signaling pathway.
FASEB J
January 2025
College of Pharmacy, Changchun University of Chinese Medicine, Jilin, China.
Xuefu Zhuyu Decoction (XZD) is widely used in the treatment of cardiovascular diseases. The purpose of this study was to explore the pharmacological effects and molecular mechanisms of XZD in improving hyperlipidemia and to provide a theoretical framework for clinical application. In this study, the signaling pathways regulated by XZD in improving hyperlipidemia were predicted by network pharmacology.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!