Systemic quercetin is associated with preservation of normal tympanic membrane morphology after myringotomy and reduced TGF-β and MMP-9 expression: a randomized controlled animal study

Myringosclerosis (MS) is an etiologically unknown disorder characterized by increased collagen tissue, hyalinization, and calcification in the tympanic membrane (TM) lamina propria. The preventive effects of many antioxidant and anti-inflammatory agents on the development of MS have been evaluated in the literature. We therefore investigated whether systemic quercetin is associated with preservation of normal TM morphology after experimental myringotomy in rats. Thirty‑six male Wistar rats were randomized to six groups ( n = 6/group): normal (NG), myringotomy control (CG), local quercetin (LQG), local vehicle (1% DMSO; LDG), systemic quercetin (SQG), and systemic vehicle (SDG). Myringosclerosis was scored otomicroscopically (0–3) on day 15. Histopathology (inflammation 0–3; MS 0–2; TM thickness, µm) and immunohistochemistry (IHC) for TGF‑β and MMP‑9 (0–3 semiquantitative scale) were performed by blinded observers. Quercetin (80 mg/kg IP every other day for 14 days) or 1% DMSO (IP) was used systemically; local groups received once‑daily ear‑canal instillations for 14 days. No residual perforations were observed. SQG and NG had similarly low otomicroscopic MS scores, while all other groups exceeded NG ( p < 0.001). TM thickness (mean ± SD) was 17.0 ± 1.0 µm (NG), 16.4 ± 2.9 µm (CG), 98.8 ± 56.9 µm (LQG), 143.7 ± 28.7 µm (LDG), 17.0 ± 3.1 µm (SQG), and 20.7 ± 5.5 µm (SDG). Histologic MS did not differ among NG, CG, and SQG; SDG exceeded NG/CG but not SQG. Inflammation was mild in NG/CG/SQG/SDG; severe in LQG/LDG ( p < 0.001). IHC showed absent/minimal staining in NG; the strongest MMP‑9 and epithelial TGF‑β immunoreactivity occurred in LDG/LQG; SQG resembled NG/CG. Systemic quercetin administration was associated with preservation of normal tympanic membrane morphology and suppression of TGF-β and MMP-9 expression in the early post-myringotomy period, suggesting a potential protective role warranting further investigation.