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LOW-DOSE LUTEOLIN FAILS TO MITIGATE DOXORUBICIN-INDUCED CARDIOVASCULAR AND PULMONARY INJURY IN RATS: HISTOPATHOLOGICAL STUDY

Kübra SEVGİN, Yağmur ÇELİK, Nur ELAGÜL TOMBUL, Ayşe KÖSE VURUŞKAN

İnönü Üniversitesi Sağlık Hizmetleri Meslek Yüksek Okulu Dergisi - 2025;13(3):778-790

University of Health Sciences, Hamidiye International Faculty of Medicine, Istanbul

 

This study aimed to evaluate the effect of luteolin (LUT) on lung, heart, and aorta histology in rats subjected to doxorubicin (DOX)-induced injury. Thirty-four 8-week-old male rats were divided into four groups: control (saline), LUT (20 mug/kg/day), DOX (5 mg/kg on days 1, 7, 14, 21, 28), and DOX+LUT (combined treatment). On day 29, rats were sacrificed for histological assessment of cardiovascular and pulmonary damage. Heart, lung, and aorta tissues were stained with Hematoxylin and Eosin (H&E), Toluidine Blue (TB), Safranin and Hemalum (SH), or Picrosirius Red (PSR). Semi-quantitative analyses of collagen and elastic fibers was performed using ImageJ. Group comparisons were made using one-way ANOVA with Bonferroni correction (p < 0.0083). DOX induced pronounced myocardial injury evidenced by loss of cross-striations, cytoplasmic vacuolization, coagulative necrosis, and an increase in collagen deposition with reduction in aortic elastic fibers and increase in aortic-collagen, as well as alveolar septal thickening, hemorrhage, and an increase in pulmonary mast cell density and interstitial collagen (all p < 0.0083). LUT treatment alone produced no histological alterations, and its co-administration at 20 µg/kg failed to ameliorate any of the DOX-induced changes. In conclusion, LUT (20 µg/kg) did not alleviate DOX-induced cardiopulmonary damage, underscoring the need for dose optimization in future studies.