Cisplatin-induced hearing loss ( CIHL ) is a serious side effect associated with chemotherapy, driven primarily by oxidative stress and chronic inflammation in the cochlea. Because astaxanthin is a potent natural antioxidant and anti-inflammatory, its ability to counteract the damaging effects of cisplatin has generated research interest.
How Astaxanthin Might Work in CIHL
1. ROS Neutralization and Antioxidant Protection
Cisplatin causes an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defenses, resulting in oxidative stress and cellular damage in the cochlea.
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Astaxanthin as a ROS scavenger:
- It protects sensory cells in the cochlea by neutralizing ROS and preventing lipid peroxidation, one of the main mechanisms of cisplatin-induced damage.
- It activates the Nrf2 antioxidant pathway, promoting the production of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx).
2. Reduction of Inflammation
Cisplatin activates microglia and local inflammation in the cochlea, exacerbating cellular damage by releasing proinflammatory cytokines (such as IL-1β, IL-6, and TNF-α).
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Astaxanthin and NF-κB inhibition:
- Suppresses the NF-κB signaling pathway, which regulates the production of inflammatory mediators.
- Reduces the expression of proinflammatory cytokines, mitigating inflammatory damage in the cochlea.
3. Mitochondrial Protection
Cisplatin-induced mitochondrial dysfunction leads to a significant increase in ROS leakage.
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Astaxanthin and mitochondrial function:
- Protects mitochondria from oxidative damage by stabilizing the electron transport chain, reducing mitochondrial ROS production.
- Preserves cellular energy levels, crucial for the viability of the sensory cells of the cochlea.
4. Regulation of ROS-Generating Enzymes
Cisplatin activates enzymes such as NADPH oxidase (NOX3) and iNOS , increasing the production of ROS and RNS (reactive nitrogen species).
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Astaxanthin and NOX3/iNOS:
- Preclinical studies have shown that astaxanthin can inhibit NOX3 activity and reduce iNOS-mediated RNS production, decreasing oxidative and inflammatory damage in the cochlea.
Preclinical Evidence of the Potential of Astaxanthin
In animal models of ototoxicity, astaxanthin has been shown to:
- Reduces hearing damage: Protects against cisplatin-induced hair cell loss, preserving hearing function.
- Mitigates oxidative and inflammatory stress: Reduces markers of oxidative damage and inflammation in the tissues of the inner ear.
- Prevents cell death: Protects sensory and support cells in the cochlea by modulating key pathways such as NF-κB and Nrf2.
Future Perspectives
While research on astaxanthin in cisplatin-induced hearing loss is in its early stages, preclinical studies suggest its potential as a natural protective agent. Its ability to act on multiple mechanisms, including ROS neutralization, inflammation reduction, and mitochondrial protection, positions it as a promising nutraceutical intervention.
However, human clinical trials are needed to confirm its efficacy, determine the optimal dose, and establish its use in combination with chemotherapy to minimize side effects without compromising the anticancer efficacy of cisplatin.
Astaxanthin, thanks to its safe profile and potent antioxidant and anti-inflammatory properties, could be an effective tool for preventing cisplatin-induced hearing loss. Its ability to protect cochlear cells from the damaging effects of cisplatin makes it a promising natural supplement for hearing care during chemotherapy treatments.
At Sevens , we explore the potential of astaxanthin and other natural antioxidants to offer solutions that protect your overall health, even in the most challenging situations like ototoxicity. Discover how this powerful carotenoid can make a difference in your recovery.