Evidence mapPaperPMID 41999431Full record

ArticleNaunyn-Schmiedeberg's archives of pharmacology2026

Rutin attenuates Tramadol-induced lung injury in rats by modulating oxidative stress, inflammation, endoplasmic reticulum stress, and apoptosis.

Mustafa Önder Gönen, Nurhan Akaras, Hasan Şimşek, Özge Kandemir, Cuneyt Caglayan, Hüseyin Mutlu, Fatih Mehmet Kandemir

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Article in Naunyn-Schmiedeberg's archives of pharmacology, 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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4 · The record

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5 · Who and what money

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7 authors.

Mustafa Önder GönenDepartment of Emergency Medicine, Meram State Hospital, Konya, Turkey.
Nurhan AkarasDepartment of Histology and Embryology, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
Hasan ŞimşekDepartment of Physiology, Faculty of Medicine, Aksaray University, Aksaray, Turkey.
Özge KandemirDepartment of Food Processing, Aksaray Technical Sciences Vocational School, Aksaray University, Aksaray, Turkey.
Cuneyt CaglayanDepartment of Medical Biochemistry, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik, Turkey.
Hüseyin MutluDepartment of Emergency Medicine, Faculty of Medicine, Aksaray University, Aksaray, Turkey. huseyinmutlu@aksaray.edu.tr.
Fatih Mehmet KandemirDepartment of Medical Biochemistry, Faculty of Medicine, Aksaray University, Aksaray, Turkey.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tramadol (TRM) is a commonly prescribed opioid analgesic; however, accumulating evidence suggests that it may exert toxic effects on vital organs, including the lungs. This study aimed to elucidate the mechanisms underlying TRM-induced lung injury and to investigate the potential protective role of rutin (RUT), a bioactive flavonoid with potent antioxidant and anti-inflammatory properties. In a rat model, lung tissues were analyzed using histopathological examination, biochemical assays for oxidative stress parameters, RT-qPCR for gene expression analysis [nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), Bax, Bcl-2, and Caspase-3], and immunohistochemical (IHC) evaluation of Beclin-1 and 3-nitrotyrosine (3-NT) expression. TRM administration caused severe pulmonary structural alterations, including alveolar collapse, interalveolar septal thickening, inflammatory infiltration, edema, and hemorrhage. These histopathological changes were associated with pronounced oxidative stress, as evidenced by suppressed superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, depletion of glutathione (GSH), increased lipid peroxidation, and disruption of the Nrf2/HO-1/NQO1 antioxidant signaling axis. Furthermore, TRM markedly activated endoplasmic reticulum (ER) stress responses (PERK and ATF-6), upregulated apoptotic markers (Bax and Caspase-3), downregulated Bcl-2 expression, and enhanced autophagy-related Beclin-1 immunoreactivity. In parallel, significant activation of inflammatory and nitrosative pathways was observed, characterized by elevated NF-κB, TNF-α, and iNOS expression and increased nitrotyrosine accumulation. In contrast, RUT treatment substantially ameliorated TRM-induced lung injury by restoring antioxidant capacity, suppressing ER stress-mediated apoptosis and autophagy, and attenuating inflammatory and nitrosative responses. Overall, these findings demonstrate that RUT confers significant protection against TRM-induced pulmonary toxicity through coordinated modulation of oxidative stress, ER stress, apoptosis, autophagy, and inflammation.

Indexed as

Anti-Inflammatory AgentsAntioxidantsLung InjuryRutinTramadolAnalgesics, OpioidAnimalsApoptosisEndoplasmic Reticulum StressInflammationLungMaleOxidative StressRatsRats, Sprague-DawleyAnalgesics, OpioidAnti-Inflammatory AgentsAntioxidantsRutinTramadolApoptosisInflammationLung toxicityOxidative stressRutinTramadol

Identifiers

PMID41999431
PMCPMC13391661

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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.