The Effect of High-Dose Paracetamol on Thyroid Gland Morphometry; Animal Experiment

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Objective: The present study aimed to investigate the histomorphological alterations induced by high-dose acetaminophen administration on the thyroid gland and trachea in rats, and to comparatively examine the protective efficacy of Vaccinium arctostaphylos (VA) fruit extract versus N-acetylcysteine (NAC). Materials and Methods: A total of 40 male Wistar albino rats were randomly assigned to five equal groups (n=8/group): Control, Acetaminophen (PCM; 2 g/kg), PCM + N-acetylcysteine (NAC; 140 mg/kg), PCM + Vaccinium arctostaphylos extract (VA; 250 mg/kg), and PCM + VA (500 mg/kg). Treatments were administered via oral gavage. After 24 hours, the thyroid gland and trachea were excised following euthanasia under high-dose anesthesia. Tissue sections (5 μm) were stained with hematoxylin-eosin and evaluated histomorphologically using a semi-quantitative scoring system. Intergroup variations were analyzed using the Kruskal-Wallis test followed by Dunn's post-hoc test with Bonferroni correction (p < 0.05). Results: High-dose paracetamol (PCM) administration induced severe tissue damage, characterized by widespread disruption of thyroid follicular architecture (2.25 ± 0.43), decreased colloid density, and variable increases in follicular epithelial cell height. Additionally, significant tracheal alterations, including pseudostratified ciliated epithelial desquamation and tracheitis (moderate in 62.5% and severe in 37.5% of rats), were observed. In contrast, the PCM + VA (500 mg/kg) and PCM + NAC groups demonstrated complete preservation of thyroid follicular regular round-oval morphology and tracheal epithelial integrity, showing no significant differences compared to the Control group ( p = 1.000, score: 0.00 ± 0.00). However, the lower dose of VA (250 mg/kg) failed to exhibit a significant protective effect, resulting in persistent follicular disruption and moderate tracheitis comparable to the PCM-only group (p = 1.000). Conclusion: High-dose paracetamol induces concurrent, severe histomorphological damage in both the thyroid gland and trachea, highlighting their vulnerability to systemic toxic stress due to close anatomical proximity. A 500 mg/kg dose of Vaccinium arctostaphylos fruit extract provides histomorphological protection comparable to N-acetylcysteine, whereas the 250 mg/kg dose is insufficient. These findings demonstrate a clear dose-dependent efficacy and suggest that VA extract holds strong therapeutic potential as a natural antioxidant counteracting paracetamol-induced organ toxicity.