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Polyphenolic compounds as protective agents against cisplatin-induced ototoxicity with molecular mechanisms and
Tong Wei1,2, Jing Nie2, Dongbo Wang2
1College of Pharmacy, Shandong University of Traditional Chinese Medicine Jinan 250355 P. R. China.
Abstract:
Cisplatin remains a cornerstone in the treatment of various solid tumors due to its exceptional antineoplastic efficacy. However, its clinical utility is significantly constrained by severe adverse effects, with ototoxicity emerging as particularly problematic due to its potential to cause permanent hearing impairment and substantially diminish patient quality of life. Recent investigations into mitigating cisplatin-induced ototoxicity have identified natural polyphenolic compounds as promising protective agents, attributable to their diverse biological activities and potent antioxidant properties. This review critically examines the molecular mechanisms underlying cisplatin-induced cochlear damage and systematically evaluates recent advances in employing polyphenolic compounds as otoprotective interventions. Evidence indicates these bioactive molecules attenuate cisplatin-mediated hearing loss through multiple complementary pathways, including modulation of oxidative stress, inflammatory responses, and apoptotic cascades within the cochlear architecture. However, significant challenges, such as low bioavailability and potential interference with cisplatin's antitumor efficacy, hinder their clinical translation. Based on evidence from studies published between 2010 and 2025, with a focus on advances from the last five years, this review systematically outlines protective mechanisms while critically addressing current research limitations. It further proposes future directions, highlighting advanced drug delivery systems and innovative therapeutic strategies. These insights provide a robust mechanistic framework for the rational design and development of novel otoprotective strategies that preserve cisplatin's antitumor efficacy while minimizing its ototoxic potential.
Insights
Natural polyphenols show promise in protecting against cisplatin-induced ototoxicity, a common side effect of cancer treatment. Further research is needed to overcome challenges for clinical use.
Area of Science:
- Pharmacology and Toxicology
- Oto-oncology
- Natural Product Chemistry
Background:
- Cisplatin is a vital chemotherapy drug for solid tumors but causes severe ototoxicity, leading to permanent hearing loss and reduced quality of life.
- Ototoxicity, a significant dose-limiting side effect of cisplatin, necessitates strategies to mitigate hearing damage without compromising anticancer efficacy.
- Natural polyphenolic compounds are being investigated for their antioxidant and anti-inflammatory properties to counteract cisplatin-induced cochlear damage.
Purpose of the Study:
- To critically review the molecular mechanisms of cisplatin-induced ototoxicity.
- To evaluate recent advancements in using polyphenolic compounds for otoprotection against cisplatin.
- To identify challenges and propose future directions for clinical translation of these protective strategies.
Main Methods:
- Systematic review of scientific literature published between 2010 and 2025, with emphasis on the last five years.
- Analysis of molecular pathways involved in cisplatin-induced cochlear damage.
- Evaluation of evidence for the otoprotective effects of various polyphenolic compounds.
Main Results:
- Polyphenols attenuate cisplatin-induced hearing loss via multiple pathways, including reducing oxidative stress, inflammation, and apoptosis in the cochlea.
- Studies indicate that these natural compounds can protect cochlear structures from chemotherapy-induced damage.
- Key challenges identified include poor bioavailability and potential interference with cisplatin's therapeutic effectiveness.
Conclusions:
- Polyphenolic compounds offer a promising therapeutic avenue for mitigating cisplatin ototoxicity.
- Overcoming bioavailability issues and ensuring preserved anticancer activity are critical for clinical application.
- Future research should focus on advanced drug delivery systems and combination strategies for effective otoprotection.
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