The protective effects of esculetin against Doxorubicin‐Induced hepatotoxicity in rats: Insights into the modulation of Caspase, FOXOs, and heat shock protein pathways.

Kizir, Duygu; Yeşilkent, Esra Nur; Öztürk, Neslihan; Karağaç, Medine Sibel; Isıyel, Murat; Tosun, Hilal; Karadaş, Habibe; Ceylan, Hamid; Karaman, Melike; Demir, Yeliz

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.

HEAT shock proteins; GENE expression; FLAVONOIDS; DOXORUBICIN; CASPASES

Journal of Biochemical & Molecular Toxicology, 2024, Vol 38, Issue 10, p1

1095-6670

Academic Journal

10.1002/jbt.23861