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oai:ebyu-rdlopen.rawdatalibrary.net:ebyu/103012026-10-18T21:13:07Zopenairedrivercom_ebyu_10000col_ebyu_10001

β-caryophyllene attenuates lead acetate-induced hepatotoxicity through regulation of oxidative stress, inflammation, and PI3K/AKT/mTOR signalingManavoğlu Kirman, EsraBolat, İsmailKaraarslan, TubaTekin, SametAtasever, AslıhanApoptosisHepatotoxicityLead acetateOxidative stressPI3K/AKT/mTOR signalingβ-CaryophylleneAnimalsAnti-Inflammatory AgentsAntioxidantsChemical and Drug Induced Liver InjuryCytokinesInflammationLiverMaleOrganometallic CompoundsPhosphatidylinositol 3-KinasePhosphatidylinositol 3-KinasesPolycyclic SesquiterpenesProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleySignal TransductionTOR Serine-Threonine Kinasesantiinflammatory agentantioxidantcaryophyllenecytokinemTOR protein, ratorganometallic compoundphosphatidylinositol 3 kinaseLead acetate (PbAc) is an environmental toxicant known to induce liver injury through oxidative stress, inflammation, and apoptosis. This study aimed to investigate the potential hepatoprotective effects of β-caryophyllene (BCP), a natural sesquiterpene with antioxidant and anti-inflammatory properties, against PbAc-induced hepatotoxicity and to explore the underlying molecular mechanisms. Sixty male Sprague–Dawley rats were randomly assigned to five groups: control, BCP200, PbAc, PbAc + BCP100, and PbAc + BCP200. PbAc was used to induce hepatotoxicity, while BCP was administered at doses of 100 and 200 mg/kg. Serum liver enzymes (ALT, AST, ALP, and GGT), oxidative stress parameters (MDA, SOD, and GSH), and inflammatory cytokines (TNF-α, IL-1β, and IL-6) were evaluated. Immunohistochemical and immunofluorescence analyses were performed to assess Nrf2, HO-1, Sirt1, Keap1, and 8-OHdG expression. In addition, the mRNA expression of PI3K, AKT, mTOR, Bax, Bcl-2, and Caspase-3 was determined by qRT-PCR, and histopathological examinations of liver tissue were conducted. PbAc exposure significantly increased serum liver enzyme levels, lipid peroxidation, and pro-inflammatory cytokines while reducing antioxidant defense markers. It also suppressed Nrf2/HO-1 signaling and PI3K/AKT/mTOR gene expression, accompanied by increased Bax and Caspase-3 and decreased Bcl-2 expression, indicating enhanced apoptosis. Histopathological analysis confirmed severe hepatic degeneration and necrosis. BCP treatment significantly attenuated these alterations by reducing oxidative stress and inflammatory responses, restoring Nrf2/HO-1 signaling, improving PI3K/AKT/mTOR pathway activity, and regulating apoptosis-related gene expression. These findings suggest that β-caryophyllene may exert protective effects against PbAc-induced hepatotoxicity through modulation of oxidative stress, inflammation, cell survival signaling, and apoptosis pathways, highlighting its potential as a supportive therapeutic candidate for heavy metal-induced liver injury. © The Author(s) 2026.Springer Science and Business Media Deutschland GmbH2026Articlehttps://rdlopen.rawdatalibrary.net/r/ebyu/10301https://doi.org/10.1007/s00210-026-05605-10028-1298enNaunyn-Schmiedeberg's Archives of Pharmacologyinfo:eu-repo/semantics/openAccessinfo:eu-repo/semantics/articlehttps://ebyu-rdlopen.rawdatalibrary.net/tr/items/ebyu/10301