TITLE:
Flavonoids as Modulators of Nrf2 Signaling Pathway in Alleviating Cisplatin-Induced Organ Toxicity
AUTHORS:
Xin Zhang, Jiwei Qian, Butian Wei, Bo Zhang
KEYWORDS:
Flavonoids, Cisplatin, Nrf2, Oxidative Stress, Natural Product
JOURNAL NAME:
Yangtze Medicine,
Vol.9 No.1,
March
5,
2025
ABSTRACT: Cisplatin, a highly efficacious platinum-based anticancer agent, finds widespread application in the management of diverse malignant solid tumors, exhibiting commendable therapeutic outcomes. However, its clinical practice is limited due to its severe adverse effects, including nephrotoxicity, hepatotoxicity, cardiotoxicity, and ototoxicity. Although the exact mechanism of cisplatin toxicity is still unclear, oxidative stress, inflammation, mitochondrial damage, endoplasmic reticulum stress (ER stress), apoptosis, and DNA damage are involved in the processes of cisplatin toxicity. At present, a great amount of evidence has shown that flavonoids have beneficial effects on several cisplatin-induced organ toxicity by their powerful antioxidant properties. The activation of Nrf2 by flavonoids could potentially serve as a key mechanism for alleviating organ toxicity induced by cisplatin. In this review, we summarize the basic structure, regulation, and function of Nrf2, as well as focus on the role of Nrf2 in reducing cisplatin-induced nephrotoxicity, hepatotoxicity, and cardiotoxicity.