Evidence map›Paper›PMID 38474165›Full record

ArticleInternational journal of molecular sciences2024

Modulating the Activity of the Human Organic Cation Transporter 2 Emerges as a Potential Strategy to Mitigate Unwanted Toxicities Associated with Cisplatin Chemotherapy.

Anna Hucke, Marta Kantauskaite, Tim N Köpp, Christoph A Wehe, Uwe Karst, Pavel I Nedvetsky, Giuliano Ciarimboli

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 45% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Anna HuckeExperimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany.
Marta KantauskaiteExperimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany.
Tim N KöppExperimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany.
Christoph A WeheInstitute of Inorganic and Analytical Chemistry, University of Münster, 48149 Münster, Germany.ORCID 0000-0001-8985-1167
Uwe KarstInstitute of Inorganic and Analytical Chemistry, University of Münster, 48149 Münster, Germany.ORCID 0000-0002-1774-6787
Pavel I NedvetskyExperimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany.ORCID 0000-0002-0572-9074
Giuliano CiarimboliExperimental Nephrology, Department of Internal Medicine D, University Hospital Münster, 48149 Münster, Germany.ORCID 0000-0002-4365-3656
University Hospital Münster · DEUniversity of Münster · DEDüsseldorf University Hospital · DE

Funding

Deutsche Forschungsgemeinschaft CI107/11-1-2 and CI107/14-1
6 · The paper itself

Abstract

Cisplatin (CDDP) stands out as an effective chemotherapeutic agent; however, its application is linked to the development of significant adverse effects, notably nephro- and ototoxicity. The human organic cation transporter 2 (hOCT2), found in abundance in the basolateral membrane domain of renal proximal tubules and the Corti organ, plays a crucial role in the initiation of nephro- and ototoxicity associated with CDDP by facilitating its uptake in kidney and ear cells. Given its limited presence in cancer cells, hOCT2 emerges as a potential druggable target for mitigating unwanted toxicities associated with CDDP. Potential strategies for mitigating CDDP toxicities include competing with the uptake of CDDP by hOCT2 or inhibiting hOCT2 activity through rapid regulation mediated by specific signaling pathways. This study investigated the interaction between the already approved cationic drugs disopyramide, imipramine, and orphenadrine with hOCT2 that is stably expressed in human embryonic kidney cells. Regarding disopyramide, its influence on CDDP cellular transport by hOCT2 was further characterized through inductively coupled plasma isotope dilution mass spectrometry. Additionally, its potential protective effects against cellular toxicity induced by CDDP were assessed using a cytotoxicity test. Given that hOCT2 is typically expressed in the basolateral membrane of polarized cells, with specific regulatory mechanisms, this work studied the regulation of hOCT2 that is stably expressed in Madin-Darby Canine Kidney (MDCK) cells. These cells were cultured in a matrix to induce the formation of cysts, exposing hOCT2 in the basolateral plasma membrane domain, which was freely accessible to experimental solutions. The study specifically tested the regulation of ASP

Indexed as

CystsOtotoxicityAnimalsCalmodulinCisplatinDisopyramideDogsHumansImipramineMadin Darby Canine Kidney CellsOrganic Cation Transporter 2Organic Cation Transport ProteinsOrphenadrineProtein-Tyrosine KinasesCalmodulinCisplatinDisopyramideImipramineOrganic Cation Transporter 2Organic Cation Transport ProteinsOrphenadrineProtein-Tyrosine Kinasescisplatincompetitionorganic cation transporterprotectionregulationtoxicitytransport

Identifiers

PMID38474165
PMCPMC10932400
OpenAlexW4392375031

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.