Effects of Ferrostatin-1 on Vocal Folds in Aging Rats

Age-related vocal fold degeneration is characterized by alterations in the lamina propria, extracellular matrix remodeling, and reduced tissue viscoelasticity, contributing to presbyphonia. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly implicated in tissue aging. This study investigated the association between ferroptosis and vocal fold aging using ferrostatin-1 (Fer-1) in a rat model.

Thirty-six male Sprague-Dawley rats were assigned to three groups: Young, Old, and Old-Fer. Fer-1 (2.5 μmol/kg, 20 μL) was injected unilaterally into the left vocal fold at Weeks 0 and 2. At Week 3, vocal folds were harvested for histological, immunohistochemical, and biochemical analyses. Outcome measures included ferroptosis-related markers, lamina propria thickness, extracellular matrix morphology, collagen and hyaluronic acid distribution, and inflammatory cytokines.

Compared with the Young group, the Old group showed increased lipid peroxidation, reactive oxygen species, and iron accumulation with reduced glutathione peroxidase 4 activity; these changes were attenuated in the Old-Fer group. The Old group also exhibited increased lamina propria thickness, enhanced collagen deposition, and reduced hyaluronic acid distribution, whereas the Old-Fer group demonstrated reduced collagen accumulation and preserved hyaluronic acid distribution. Transforming growth factor-β and interleukin-1β expression levels were elevated in the Old group and reduced following Fer-1 treatment.

The results indicate that ferroptosis is involved in vocal fold aging. In addition, Fer-1 effectively suppressed ferroptotic pathways, which may be associated with the attenuation of aging-related extracellular matrix alterations in the vocal folds.

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