β-caryophyllene attenuates lead acetate-induced hepatotoxicity through regulation of oxidative stress, inflammation, and PI3K/AKT/mTOR signaling.

Authors

Esra Manavoğlu Kirman, İsmail Bolat, Tuba Karaarslan, Samet Tekin, Aslıhan Atasever

Published in

Naunyn-Schmiedeberg's archives of pharmacology. Jun 25, 2026. Epub Jun 25, 2026.

Abstract

Lead 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.

PMID:
42347875
Bibliographic data and abstract were imported from PubMed on 25 Jun 2026.

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