Evidence mapPaperPMID 42352253Full record

ArticleBiomolecules2026

Targeting Oxidative Stress and Inflammation in Pembrolizumab-Induced Renal Injury: A Comparative Evaluation of the Protective Effects of Flunarizine and Carvacrol in Rats.

Engin Hendem, Bulent Yavuzer, Esra Tuba Sezgin, Murat Gunay, Mustafa Ozkaraca, Ali Gungor, Durdu Altuner, Halis Suleyman

Abstract readComparative Study
In one paragraph

Article in Biomolecules, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Engin HendemDepartment of Medical Oncology, Mengucek Gazi Education and Research Hospital, Erzincan Binali Yıldırım University, Erzincan 24100, Turkey.
Bulent YavuzerDepartment of Pharmacology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, Turkey.ORCID 0000-0001-7576-0678
Esra Tuba SezginAnesthesia Program, Vocational School of Health Services, Erzincan Binali Yıldırım University, Erzincan 24036, Turkey.ORCID 0000-0003-3491-9798
Murat GunayBiochemistry Laboratory, Mengucek Gazi Education and Research Hospital, Erzincan Binali Yıldırım University, Erzincan 24100, Turkey.
Mustafa OzkaracaDepartment of Pathology, Faculty of Veterinary Medicine, Sivas Cumhuriyet University, Sivas 58140, Turkey.ORCID 0000-0002-6359-6249
Ali GungorLaboratory and Veterinary Health Program, Vocational School of Health Services, Osmaniye Korkut Ata University, Osmaniye 80000, Turkey.ORCID 0009-0008-7985-0986
Durdu AltunerDepartment of Pharmacology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, Turkey.ORCID 0000-0002-5756-3459
Halis SuleymanDepartment of Pharmacology, Faculty of Medicine, Erzincan Binali Yıldırım University, Erzincan 24100, Turkey.ORCID 0000-0002-9239-4099

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, is widely employed in oncological practice; however, its propensity to induce nephrotoxicity through immune-mediated oxidative and inflammatory mechanisms remains an insufficiently characterized clinical concern. The present study comparatively investigated the renoprotective effects of flunarizine, a voltage-dependent calcium channel antagonist, and carvacrol, a monoterpene, against pembrolizumab-induced renal injury in rats.

methodsTwenty-four male Wistar albino rats were assigned to four groups (

resultsPembrolizumab caused pronounced oxidative stress and inflammatory responses in renal tissue, leading to a significant increase in renal MDA levels and a marked decrease in tGSH levels. These biochemical alterations were accompanied by severe tubular degeneration and increased expression of 3,3'-dityrosine, which is associated with oxidative damage, as well as HAVCR1, a marker of cellular injury, and COX-1 and COX-2, which reflect inflammatory activity. These findings indicate that pembrolizumab disrupts the renal redox balance and activates both oxidative and inflammatory pathways in kidney tissue. Flunarizine and carvacrol significantly reduced these pathological changes. Both agents attenuated oxidative stress markers and supported antioxidant defenses, thereby alleviating tissue damage. However, flunarizine demonstrated a more pronounced renoprotective effect across all evaluated parameters, restoring MDA and tGSH levels closer to physiological values and reducing tubular injury to a minimal level. Carvacrol showed a more limited but still statistically significant protective effect.

conclusionsBoth agents confer significant renoprotection against pembrolizumab-induced oxidative injury; however, flunarizine exhibits a more robust protective profile, likely attributable to its capacity to attenuate calcium-mediated mitochondrial dysfunction and preserve cellular bioenergetic homeostasis.

Indexed as

Antibodies, Monoclonal, HumanizedCymenesInflammationOxidative StressAnimalsGlutathioneKidneyMaleRatsRats, WistarAntibodies, Monoclonal, HumanizedcarvacrolCymenesGlutathione3,3′-dityrosinecarvacrolcyclooxygenase-1/cyclooxygenase-2double immunofluorescenceflunarizinehepatitis A virus cellular receptor 1immune checkpoint inhibitorsnephrotoxicityoxidative stresspembrolizumab

Identifiers

PMID42352253
PMCPMC13296656

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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.