Protective Effects of Phenytoin and Spironolactone against 5-Fluorouracil-induced Alopecia: Involvement of Antioxidant, Anti-inflammatory, and Collagen-regenerative Mechanisms.

Authors

Onaolapo J Olakunle, Ogundiran J Reuben, Olofinnade T Anthony, Onaolapo Y Adejoke

Published in

Anti-inflammatory & anti-allergy agents in medicinal chemistry. Oct 06, 2026. Epub Oct 06, 2026.

Abstract

Chemotherapy-induced alopecia (CIA) is one of the most distressing adverse effects of cancer treatment and is primarily associated with oxidative stress, inflammation, and damage to hair follicles. Effective preventive and therapeutic options remain limited. This study evaluated the protective effects of oral phenytoin and spironolactone against 5-fluorouracil (5-FU)- induced alopecia in rats.
CIA was induced in rats using intraperitoneal administration of 5-FU, followed by daily oral treatment with phenytoin or spironolactone for 21 days. Feed intake, body weight, and hair regrowth were monitored throughout the study. Blood and skin samples were collected for assessment of oxidative stress markers, inflammatory cytokines, and histological changes using Haematoxylin and Eosin and Von Gieson staining.
5-FU administration significantly reduced feed intake and body weight and induced marked alopecia, impaired hair regrowth, and follicular degeneration. Treatment with phenytoin and spironolactone improved appetite, attenuated weight loss, and enhanced hair regrowth. Both agents significantly reduced oxidative stress, as evidenced by decreased plasma malondialdehyde (MDA) levels, lowered TNF-α and IL-1β concentrations, and restored IL-10 levels. Histological analyses revealed that 5-FU caused dermal papilla distortion, follicular shrinkage, loss of anagen follicles, and disruption of collagen organization. These alterations were markedly ameliorated by both treatments, with improved follicular architecture, hair shaft integrity, collagen organization, and anagen activity. Phenytoin produced greater improvements in selected hair morphometric indices.
The findings indicate that attenuation of oxidative stress and inflammation was accompanied by improved follicular structure and hair regrowth, suggesting that these mechanisms may contribute to the protective effects of both agents. The greater improvement in selected morphometric indices with phenytoin indicates potentially differential effects on follicular recovery.
Phenytoin and spironolactone effectively attenuated 5-FU-induced alopecia, oxidative stress, inflammation, and follicular damage. Their protective effects suggest potential therapeutic utility in promoting post-chemotherapy hair recovery and improving treatment outcomes.

PMID:
42864925
Bibliographic data and abstract were imported from PubMed on 13 Oct 2026.

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