Article 2025 · 2 citations

Mechanistic insights into the P-coumaric acid protection against bisphenol A-induced hepatotoxicity in in vivo and in silico models

Tekin, Samet, Bolat, Merve, Atasever, Aslihan, Bolat, Ismail, Cinar, Burak, Shadidizaji, Azizeh, Dag, Yusuf, Sengul, Emin, Yildirim, Serkan, Hacimuftuoglu, Ahmet, Warda, Mohamad

Abstract

Bisphenol A (BPA), commonly found in plastic containers and epoxy resins used for food products, presents substantial health risks, particularly in relation to hepatic toxicity. This study investigates BPA-induced liver damage and explores the mechanistic dose-dependent protective effects of P-coumaric acid (PCA). 50 male rats were divided into control, BPA-treated, BPA + PCA50, BPA + PCA100, and PCA100 groups. BPA exposure for 14 days induced oxidative stress, evidenced by elevated malondialdehyde levels and decreased activities of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, and catalase). Higher doses of PCA effectively mitigated these effects by restoring redox balance and enhancing antioxidant enzyme activities. Additionally, BPA disrupted inflammation and apoptosis pathways, inhibiting anti-inflammatory markers and interfering with the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway. PCA exhibited dose-dependent protection against these disruptions. Computational analyses revealed that BPA inhibits cyclooxygenase-1 through stable hydrogen bonding with threonine at position 322. PCA's dual protective effect was confirmed by attenuating inflammatory pathways, including TNF-alpha inhibition and suppression of the Kelch-like ECH-associated protein 1 (KEAP1) and Nrf2 signaling pathway. Histopathological assessments confirmed that PCA alleviated significant hepatic damage induced by BPA. Immunohistochemical and immunofluorescence analyses further supported PCA's protective role against BPA-induced apoptosis and cellular hepatotoxicity. These findings underscore PCA's protective potential against BPA-induced hepatotoxicity and highlight novel mechanistic interactions that warrant further investigation in applied nutritional biochemistry.

Keywords

Apoptosis Bisphenol A In silico Inflammation Oxidative stress P-Coumaric acid OXIDATIVE STRESS INDUCED NEPHROTOXICITY TOXICITY LIVER RATS PATHWAY APOPTOSIS EXPOSURE KINETICS DOCKING

WoS Categories

Multidisciplinary Sciences

Sustainable Development Goals

Good Health and Well-being Clean Water and Sanitation

Citation

Journal: SCIENTIFIC REPORTS
Year: 2025
Volume: 15
Issue: 1
ISSN: 2045-2322
DOI: 10.1038/s41598-025-87099-0
WoS UID: WOS:001456731400039

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