Evidence map›Paper›PMID 42434130›Full record

ArticleFrontiers in pharmacology2026

Investigation of potential sex-based differences in trastuzumab-induced chronic cardiotoxicity in a rat model.

Réka Losonczi, Zsolt Galla, Merse Kis, Klaudia Kupecz, Dávid Volford, Andrea Siska, Réka Somogyi, Imre Földesi, Gábor Cserni, András Kriston and 5 more

Erratum issuedAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Réka LosoncziCardiovascular Research Group, Department of Pathophysiology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Zsolt GallaMetabolic and Newborn Screening Laboratory, Department of Pediatrics, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Merse KisCardiovascular Research Group, Department of Pathophysiology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Klaudia KupeczCardiovascular Research Group, Department of Pathophysiology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Dávid VolfordCardiovascular Research Group, Department of Pathophysiology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Andrea SiskaDepartment of Laboratory Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Réka SomogyiCardiovascular Research Group, Department of Pathophysiology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Imre FöldesiDepartment of Laboratory Medicine, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Gábor CserniDepartment of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
András KristonSynthetic and Systems Biology Unit, HUN-REN Biological Research Centre, Szeged, Hungary.
Ferenc KovácsSynthetic and Systems Biology Unit, HUN-REN Biological Research Centre, Szeged, Hungary.
Péter HorváthSynthetic and Systems Biology Unit, HUN-REN Biological Research Centre, Szeged, Hungary.
Péter MonostoriMetabolic and Newborn Screening Laboratory, Department of Pediatrics, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Zsuzsanna KahánDepartment of Oncotherapy, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.
Márta SárközyCardiovascular Research Group, Department of Pathophysiology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Although trastuzumab (TZB) significantly increases survival in patients with human epidermal growth factor receptor 2 (HER2/ErbB2)-positive breast and gastrointestinal cancers, its use may be limited by chronic cardiotoxicity. Several tryptophan (Trp) metabolites are associated with oxidative stress, inflammation, and metabolic disturbances in heart failure (HF). Here, we aimed to characterize changes in left ventricular (LV) concentrations of selected Trp metabolites in a rat model of TZB-induced chronic cardiotoxicity. Methods: Male and female Wistar-Hannover rats (300-400 g) were divided into 2-2 groups: i) physiological saline-treated (6 × 1 mL/kg, i.p.) control, and ii) TZB-treated (2 mg/kg, then 5 × 1 mg/kg, i.p.) groups. At weeks 12 and 19, echocardiography was performed. At week 20, blood and LV samples were collected. Then, histology, RT-qPCR, and UHPLC-MS/MS analyses of genes and metabolites related to nitro-oxidative stress, inflammation, glucose and fatty acid metabolism, and Trp metabolism were performed. Results: Diastolic dysfunction began in both TZB-treated groups by week 12. At the endpoint, both TZB-treated groups showed echocardiographic, histologic, and molecular signs of chronic cardiotoxicity, accompanied by LV overexpression of genes associated with inflammation and nitro-oxidative stress, repression of glucose transporter 4, glycerol-3-phosphate dehydrogenase, and carnitine palmitoyltransferase. However, only female TZB-treated rats showed increased LV levels of Trp, 3-hydroxykynurenine, quinolinic acid, and nicotinamide adenine dinucleotide (NAD Conclusion: Comparable TZB-induced chronic cardiotoxicity developed in both sexes. However, LV Trp metabolite concentrations showed sex-divergent alterations, the significance of which should be clarified in further mechanistic studies.

Indexed as

glucose and fatty acid metabolismheart failurekynurenine pathwaytrastuzumabtrastuzumab-induced chronic cardiotoxicitytryptophan and arginine metabolites

Identifiers

PMID42434130
PMCPMC13349826

What Socratic holds

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Registered trials

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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.