Faculty of Science, Department of Molecular Biology and Genetics, Atatürk University, Erzurum, Türkiye.
Department of Pharmacy Services, Nihat Delibalta Göle Vocational High School, Ardahan University, Ardahan, Türkiye.
J Biochem Mol Toxicol. 2024 Oct;38(10):e23861. doi: 10.1002/jbt.23861.
Doxorubicin (DOX) is an anthracycline antibiotic widely employed to treat carcinoma. Nevertheless, severe cardiotoxic side effects restrict its clinical use. Esculetin, a natural flavonoid, is found abundantly in plants. This study evaluated the protective effects of esculetin against DOX-induced hepatotoxicity in rat livers. Forty-eight rats were randomly divided into six groups with eight rats in each group: control (I), DOX (II), esculetin (III, 50 mg/kg), esculetin (IV, 100 mg/kg), DOX+esculetin 50 (V, DOX+esculetin 50 mg/kg), and DOX+esculetin 100 (VI, DOX+esculetin 100 mg/kg). The administration of esculetin effectively mitigated alterations in the measured biochemical parameters induced by DOX. Gene expression analyses demonstrated that esculetin treatment significantly reduced the DOX-induced expression of Foxo1, Hspa1a, Hsp4a, Hsp5a, Casp3, and Casp9 while increasing the DOX-induced expression of Foxo3. These findings suggest that esculetin, with its antioxidant and anti-inflammatory effects, might be a therapeutic option for protecting against DOX-induced hepatotoxicity.
多柔比星（DOX）是一种广泛用于治疗癌的蒽环类抗生素。然而，严重的心脏毒性副作用限制了其临床应用。秦皮素是一种天然黄酮类化合物，在植物中含量丰富。本研究评估了秦皮素对 DOX 诱导的大鼠肝脏毒性的保护作用。48 只大鼠随机分为 6 组，每组 8 只：对照组（I）、DOX 组（II）、秦皮素 50mg/kg 组（III）、秦皮素 100mg/kg 组（IV）、DOX+秦皮素 50mg/kg 组（V）和 DOX+秦皮素 100mg/kg 组（VI）。秦皮素的给药有效减轻了 DOX 引起的测定生化参数的变化。基因表达分析表明，秦皮素处理显著降低了 DOX 诱导的 Foxo1、Hspa1a、Hsp4a、Hsp5a、Casp3 和 Casp9 的表达，同时增加了 DOX 诱导的 Foxo3 的表达。这些发现表明，秦皮素具有抗氧化和抗炎作用，可能是预防 DOX 诱导的肝毒性的一种治疗选择。
