ArticleAntimicrobial agents and chemotherapy2016
Organic Cation Transporter 2 Overexpression May Confer an Increased Risk of Gentamicin-Induced Nephrotoxicity.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 52 citations in OpenAlex.
- Megalin: from structure to function.Nature reviews. Nephrology · 2026Review
- Interindividual variability in metformin pharmacokinetics in pediatric patients.Pediatric research · 2026Article
- The Impact of Drug Properties and Severity of Obesity on Renal Drug Clearance Through Glomerular Filtration and Active Tubular Secretion: A Systematic Analysis Using PBPK Modeling.Pharmaceutical research · 2025Article
- Pharmacotherapy in kidney disease: what it takes to move from general guidance to specific recommendations to stratified subgroups of patients - the tale of autosomal dominant polycystic kidney disease (ADPKD).Expert opinion on drug metabolism & toxicology · 2025Review
- The landscape of renal protein S-acylation in mice with lipid-induced nephrotoxicity.Scientific reports · 2025Article
- Spatio-temporal transcriptomic analysis reveals distinct nephrotoxicity, DNA damage, and regeneration response after cisplatin.Cell biology and toxicology · 2025Article
- L-carnitine co-administration prevents colistin-induced mitochondrial permeability transition and reduces the risk of acute kidney injury in mice.Scientific reports · 2024Article
- Characterization of ligand-induced thermal stability of the human organic cation transporter 2 (OCT2).Frontiers in pharmacology · 2023Article
- Bile duct ligation differently regulates protein expressions of organic cation transporters in intestine, liver and kidney of rats through activation of farnesoid X receptor by cholate and bilirubin.Acta pharmaceutica Sinica. B · 2023Article
- Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression.Genome research · 2022Article
- Localization of Xenobiotic Transporters Expressed at the Human Blood-Testis Barrier.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- The Role of NF-kB in the Downregulation of Organic Cation Transporter 2 Expression and Renal Cation Secretion in Kidney Disease.Frontiers in medicine · 2021Article
- Drug Transporters in the Kidney: Perspectives on Species Differences, Disease Status, and Molecular Docking.Frontiers in pharmacology · 2021Review
- Equine Drug Transporters: A Mini-Review and Veterinary Perspective.Pharmaceutics · 2020Review
- Dose recommendations for gentamicin in the real-world obese population with varying body weight and renal (dys)function.The Journal of antimicrobial chemotherapy · 2020Article
- Organic Cation Transporters in Human Physiology, Pharmacology, and Toxicology.International journal of molecular sciences · 2020Review
- Drug Elimination Alteration in Acute Lymphoblastic Leukemia Mediated by Renal Transporters and Glomerular Filtration.Pharmaceutical research · 2020Article
- The Role of Mitochondria in Drug-Induced Kidney Injury.Frontiers in physiology · 2020Review
- A Prospective Clinical Study Characterizing the Influence of Morbid Obesity on the Pharmacokinetics of Gentamicin: Towards Individualized Dosing in Obese Patients.Clinical pharmacokinetics · 2019Article
- Tobramycin Clearance Is Best Described by Renal Function Estimates in Obese and Non-obese Individuals: Results of a Prospective Rich Sampling Pharmacokinetic Study.Pharmaceutical research · 2019Observational
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nephrotoxicity is a relevant limitation of gentamicin, and obese patients have an increased risk for gentamicin-induced kidney injury. This damage is thought to depend on the accumulation of the drug in the renal cortex. Obese rats showed substantially higher levels of gentamicin in the kidney than did lean animals. This study characterized the role of organic cation transporters (OCTs) in gentamicin transport and elucidated their possible contribution in the increased renal accumulation of gentamicin in obesity. The mRNA and protein expression levels of the organic cation transporters Oct2 (Slc22a2) and Oct3 (Slc22a3) were increased in kidney samples from obese mice fed a high-fat diet. Similarly, OCT2 (∼2-fold) and OCT3 (∼3-fold) showed increased protein expression in the kidneys of obese patients compared with those of nonobese individuals. Using HEK293 cells overexpressing the different OCTs, human OCT2 was found to transport [(3)H]gentamicin with unique sigmoidal kinetics typical of homotropic positive cooperativity (autoactivation). In mouse primary proximal tubular cells, [(3)H]gentamicin uptake was reduced by approximately 40% when the cells were coincubated with the OCT2 substrate metformin. The basolateral localization of OCT2 suggests that gentamicin can enter proximal tubular cells from the blood side, probably as part of a slow tubular secretion process that may influence intracellular drug concentrations and exposure time. Increased expression of OCT2 may explain the higher accumulation of gentamicin, thereby conferring an increased risk of renal toxicity in obese patients.
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