LUTEOLİN DOKSORUBİSİN KAYNAKLI TİROİT TOKSİSİTESİNE KARŞI KORUYUCU MUDUR? DENEYSEL BULGULAR DOZ SINIRLAMALARINA İŞARET EDİYOR

Objective: Doxorubicin (DOX) is a chemotherapeutic agent known to cause multi-organ toxicity, including thyroid dysfunction. While biochemical evidence of DOX-induced hypothyroidism exists, histopathological changes and apoptosis regulation in the thyroid remain poorly understood. In addition; although luteolin (LUT) shows protective effects in other tissues, its role against DOX-induced thyroid injury has not yet been studied in vivo. This study aimed to evaluate the protective effects of LUT on DOX-induced thyroid damage in rats, focusing on histopathology, apoptosis, and inflammation. Methods: Adult male Sprague Dawley rats were divided into four groups: control, DOX (5 mg/kg, i.p.), LUT (administered at 20 μg/kg), and DOX+LUT (combined treatment). On day 29 thyroid tissues were harvested. Histopathological evaluation included hematoxylin-eosin (H&E), Periodic-acid Shiff (PAS) and Toluidine Blue (TB) staining and immunofluorescence analysis for Bax and Bcl2 expression. The Bax/Bcl2 ratio was calculated to quantify apoptosis. Results: DOX administration induced marked apoptotic changes in thyroid tissue, reflected by an increased Bax/Bcl2 ratio, without evidence of mast cell infiltration. LUT treatment alone produced no morphological alterations, including follicular damage or colloid deposition. Although co-treatment with LUT enhanced Bcl2 expression, it did not significantly reduce the Bax/Bcl2 ratio. Chronic DOX exposure induces marked apoptosis and histopathological alterations in thyroid tissues of rats. Conclusion: LUT at the tested dose partially enhanced Bcl2 expression but did not reduce apoptosis or prevent histopathological damage, indicating limited protective efficacy. These findings suggest the need for dose optimization and further investigation in future studies.