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

Kizir D., Yeşilkent E. N., Öztürk N., Karağaç M. S., Isıyel M., Tosun H., ...Daha Fazla

Journal of biochemical and molecular toxicology, cilt.38, sa.10, 2024 (SCI-Expanded, Scopus) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 38 Sayı: 10
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1002/jbt.23861
  • Dergi Adı: Journal of biochemical and molecular toxicology
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Environment Index, Food Science & Technology Abstracts, MEDLINE
  • Anahtar Kelimeler: Caspase, doxorubicin, esculetin, heat shock protein
  • Atatürk Üniversitesi Adresli: Evet

Özet

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.