The M1/M2 Macrophage Polarization and Hepatoprotective Activity of Quercetin in Cyclophosphamide-Induced Experimental Liver Toxicity

dc.authoridUyar, Emre/0000-0001-9941-1237
dc.authoridGokdemir, Gul Sahika/0000-0002-8691-1504
dc.authoridSeker, Ugur/0000-0002-1693-6378
dc.authoridKavak, Deniz Evrim/0000-0002-9681-4468
dc.contributor.authorSeker, Ugur
dc.contributor.authorUyar, Emre
dc.contributor.authorGokdemir, Gul Sahika
dc.contributor.authorKavak, Deniz Evrim
dc.contributor.authorIrtegun-Kandemir, Sevgi
dc.date.accessioned2025-02-22T14:09:08Z
dc.date.available2025-02-22T14:09:08Z
dc.date.issued2025
dc.departmentDicle Üniversitesien_US
dc.description.abstractBackground: Chemotherapy drugs may lead to hepatic injury, which is considered one of the limitations of these drugs. Objectives: The aim of this study was to evaluate the effect of quercetin (QUE) on M1/M2 macrophage polarization and hepatoprotective effect in cyclophosphamide (CTX)-induced liver toxicity. Methods: Twenty-four mice were divided into four groups (Control, QUE, CTX, CTX + QUE). The CTX and CTX + QUE groups received 200 mg/kg CTX. The animals in the QUE and CTX + QUE groups received 50 mg/kg QUE. All animals were sacrificed, and serum and liver samples were used for laboratory analyses. Results: Examinations indicated that CTX exposure led to disruption of liver functions and morphological degenerations. Tissue pro-apoptotic Bax and caspase 3, pro-inflammatory TNF-alpha and IL-1 beta, transcription factor NF-kappa B, and M1 macrophage polarization marker CD86 were upregulated significant (p < 0.05) in this group. In addition, CTX exposure led to significantly (p < 0.05) upregulation of the Bax/Bcl-2 mRNA ratio and DNA fragmentations. The PCNA-positive hepatic cell ratio and anti-apoptotic Bcl-2 expression are remarkably suppressed (p < 0.05). Immunohistochemical analyses are also indicated that M2 macrophage polarization marker CD163 is slightly but remarkably (p < 0.05) downregulated in the CTX group compared to the Control and QUE groups. The morphological and biochemical disruptions were alleviated in QUE-treated animals in the CTX + QUE group. Liver function test results, apoptosis, inflammatory, transcription factor NF-kappa B, regeneration/proliferation, and apoptotic index results in this group were similar (p > 0.05) to the control and QUE groups. The M1 cell surface marker expression of CD86 is significantly (p < 0.05) downregulated, and M2 macrophage polarization marker expression of CD163 is upregulated significantly (p < 0.05) compared to the CTX group. Conclusions: This study indicates that QUE has the potential to downregulate CTX-induced hepatic injury and regulate M1/M2 macrophage polarization to the M2 side, which indirectly demonstrates activation of anti-inflammatory signalling and tissue repair.en_US
dc.identifier.doi10.1002/vms3.70183
dc.identifier.issn2053-1095
dc.identifier.issue1en_US
dc.identifier.pmid39792066en_US
dc.identifier.scopus2-s2.0-85214875949en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1002/vms3.70183
dc.identifier.urihttps://hdl.handle.net/11468/29807
dc.identifier.volume11en_US
dc.identifier.wosWOS:001395114400001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofVeterinary Medicine and Scienceen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.snmzKA_WOS_20250222
dc.subjectapoptosisen_US
dc.subjectcyclophosphamideen_US
dc.subjectinflammationen_US
dc.subjectliver toxicityen_US
dc.subjectquercetinen_US
dc.titleThe M1/M2 Macrophage Polarization and Hepatoprotective Activity of Quercetin in Cyclophosphamide-Induced Experimental Liver Toxicityen_US
dc.typeArticleen_US

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