Protective Effect of HMG-CoA Reductase Inhibitor Rosuvastatin on Doxorubicin-Induced Cognitive Impairment, Oxidative Stress and Neuroinflammation: Possible Role of CREB, ERK1/2, and BDNF

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dc.contributor.authorYeni, Yesim
dc.contributor.authorCicek, Betul
dc.contributor.authorHacimuftuoglu, Ahmet
dc.contributor.authorOzkaraca, Mustafa
dc.contributor.authorLacin, Burak Batuhan
dc.date.accessioned2026-06-19T06:41:04Z
dc.date.available2026-06-19T06:41:04Z
dc.date.issued2025
dc.departmentMalatya Turgut Özal Üniversitesi
dc.description.abstractDuring or after chemotherapy, cognitive impairments characterized by forgetfulness, difficulty concentrating, and depressive and anxiety-like symptoms are observed. There is limited research examining the effects of rosuvastatin (RVS), an HMG-CoA reductase inhibitor, in the context of neuroinflammation-related cognitive disruption. Here, we aimed to investigate the neuroprotective potential of RVS against doxorubicin (DOX)-induced cognitive impairments. Experimental groups were planned as control (normal saline, intraperitoneal), DOX (total cumulative dose 10 mg/kg, intraperitoneal), RVS (10 mg/kg, oral, 20 days), and RVS + DOX. Efficacy was monitored by applying a battery of behavioral assessments, as well as biochemical, genetic, histopathological, and immunohistochemical examinations. Results from Morris water maze (MWM), passive avoidance, locomotion activity, and elevated plus maze (EPM) tests showed that DOX administration caused behavioral disorders. Moreover, DOX increased the levels of inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-alpha), while decreasing the levels of interleukin-10 (IL-10), glutathione (GSH), superoxide dismutase, catalase (SOD), endothelial nitric oxide (eNOS), and catalase (CAT). Co-treatment with RSV significantly attenuated DOX-induced behavioral changes and oxidative stress markers. In addition, similar to the immunohistochemical results, we determined that it increased the expression levels of extracellular signal-related kinases 1/2 (ERK1/2), cyclic adenosine monophosphate response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) and restored the histopathological structure of the brain. Therefore, these results indicated that RSV has a neuroprotective effect against DOX-induced cognitive impairment by reducing neurobehavioral impairments, exerting antioxidant and anti-inflammatory effects, and modulating brain growth factors.Graphical AbstractRSV ameliorated DOX-induced cognitive impairments by assessing oxidative stress, BDNF, CREB, and ERK1/2 expression. These beneficial effects induced by RSV provided strong protection against both cognitive dysfunction and anxiety-like behavior. RSV may help prevent or alleviate cognitive dysfunction in patients with various types of cancer undergoing chemotherapy and may have potential benefit in neurodegenerative diseases
dc.description.sponsorshipScientific and Technological Research Council of Turkiye (TUBIdot;TAK)
dc.description.sponsorshipOpen access funding provided by the Scientific and Technological Research Council of Turkiye (TUB & Idot;TAK). This research received no external funding.
dc.identifier.doi10.1007/s11481-025-10213-6
dc.identifier.issn1557-1890
dc.identifier.issn1557-1904
dc.identifier.issue1
dc.identifier.orcid0000-0002-5701-3684
dc.identifier.orcid0000-0002-6719-7077
dc.identifier.pmid40358798
dc.identifier.scopus2-s2.0-105004909377
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1007/s11481-025-10213-6
dc.identifier.urihttps://hdl.handle.net/20.500.12899/6046
dc.identifier.volume20
dc.identifier.wosWOS:001487356200001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofJournal of Neuroimmune Pharmacology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20260612
dc.subjectCognitive Impairment
dc.subjectDoxorubicin
dc.subjectNeuroinflammation
dc.subjectNeuroplasticity
dc.subjectRosuvastatin
dc.titleProtective Effect of HMG-CoA Reductase Inhibitor Rosuvastatin on Doxorubicin-Induced Cognitive Impairment, Oxidative Stress and Neuroinflammation: Possible Role of CREB, ERK1/2, and BDNF
dc.typeArticle

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