ArticleFrontiers in pharmacology2025
Prevention of chemotherapy drug-mediated human hair follicle damage: combined use of cooling with antioxidant suppresses oxidative stress and prevents matrix keratinocyte cytotoxicity.
Article in Frontiers in pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
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4 authors.
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Abstract
Background: Chemotherapy-induced alopecia (CIA) is a distressing side-effect of cancer treatment. Scalp cooling remains the only available method to mitigate CIA, but its effectiveness varies amongst patients. We previously reported that the cytoprotective effects of cooling are temperature dependent. Here we investigated whether blockade of reactive oxygen species (ROS) by antioxidants can potentiate cooling-mediated cytoprotection against chemotherapy-induced damage in human keratinocytes and hair follicles (HFs). Methods: Results: Chemotherapy agents reduced keratinocyte viability at 37°C by ∼65%-70%, induced HF dystrophy evident by decreased proliferation (9% Ki-67+ cells), increased apoptosis (23% TUNEL+ cells), and reduced anagen (∼10%) and pigmentation. Optimal cooling at 18°C rescued cell viability, significantly (p < 0.001) restored HF proliferation (42% Ki-67+ cells) and pigmentation, suppressed apoptosis (10% TUNEL+ cells), restored anagen (∼70%) and induced a 2-3-fold increase in hair shaft elongation (p < 0.001), whereas cooling at 26°C was only partially effective. ROS generation increased >3-fold following drug exposure and was attenuated by cooling in a temperature-dependent fashion (p < 0.001). Co-treatment with antioxidant (such as N-acetylcysteine) at 26°C restored cell viability to levels comparable with 18°C, normalizing HF proliferation (41% Ki-67+ cells), suppressing apoptosis (8% TUNEL+ cells) and restoring HF function (e.g., hair shaft elongation, p < 0.001). Conclusion: Cooling effectively suppresses chemotherapy drug-induced cytotoxicity in human keratinocytes and HFs in a temperature-dependent manner. Combination of cooling with antioxidant functionally compensates for inadequate cytoprotection under sub-optimal cooling conditions, as it prevents HF cell apoptosis and maintains HF viability (proliferation) and functionality (hair growth). This combinatorial approach holds translational promise for improving the efficacy and consistency of scalp cooling in preventing CIA, ultimately improving cancer patient quality-of-life during chemotherapy treatment.
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