Article 2025 · 2 citations

Zingerone ameliorates sodium arsenite-induced cardiotoxicity in rats by suppressing oxidative stress and inflammation via Nrf2 /GCLM\GCLC signaling pathways

Kandemir, Ozge, Kandemir, Fatih Mehmet, Akaras, Nurhan, Kucukler, Sefa, Gur, Cihan, Ileriturk, Mustafa, Simsek, Hasan, Gul, Murat

Abstract

Arsenic toxicity is a serious threat to human health, transmitted through many factors in the environment, especially water and contaminated food. Epidemiologic studies have reported that arsenite increases mortality and morbidity by causing cardiac damage, but the mechanism of action on cardiotoxicity remains to be elucidated. Zingerone (ZNG) obtained from ginger root is a monomer with pharmacological effects such as antioxidant, anti-inflammatory, and anticancer. This study was conducted to investigate the protective potential of zingerone against sodium arsenite-induced cardiac damage in rats. Sodium arsenite (SA) (10 mg/kg) was administered to rats for 14 days to induce cardiotoxicity, while zingerone (25 and 50 mg/kg) was administered for treatment. Then, oxidative stress markers, inflammatory factors, and apoptosis-related proteins were evaluated by molecular and biochemical methods. It was also supported by histological and immunohistochemical stainings. According to the results, ZNG treatment significantly reduced SA-induced altered cardiac functions. Compared with the SA group, rats co-treated with SA and ZNG showed a significant decrease in oxidant markers and an increase in antioxidant levels. Additionally, ZNG treatment regulated the expression of NRF2, HO-1, NQO1, GCLM, and GCLC genes related to oxidative stress. Moreover, treatment with ZNG significantly inhibited arsenite-induced apoptosis (p53, Apaf-1, Bax, Bcl-2, Casp-3, Casp-6, Casp-9) while reducing the levels of inflammatory mediators including NF-kappa B, TNF-alpha, IL-1 beta, COX-2 and iNOS in cardiac tissue. Finally, coadministration of ZNG with SA reduced SA-induced cardiac histopathological changes in rats. The results of this study suggest that ZNG may provide an alternative for clinical inflammation control through antioxidant and anti-inflammatory activities.

Keywords

Sodium arsenite Zingerone Cardiotoxicity Oxidative stress Inflammation DAMAGE TOXICITY LIVER DYSFUNCTION CASPASE-3 NARINGIN ACID

WoS Categories

Biochemistry & Molecular Biology Endocrinology & Metabolism

Sustainable Development Goals

Clean Water and Sanitation Good Health and Well-being

Citation

Journal: JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY
Year: 2025
Volume: 91
ISSN: 0946-672X
eISSN: 1878-3252
DOI: 10.1016/j.jtemb.2025.127716
WoS UID: WOS:001579391500002

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