Gentisic acid attenuates 5-fluorouracil-induced ovotoxicity in rats via modulating Nrf2 signalling: An experimental approach


MENTEŞE A., DEMİR S., YULUĞ E., Kucuk H., Alemdar N. T., Demir E., ...Daha Fazla

REPRODUCTIVE TOXICOLOGY, cilt.128, 2024 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 128
  • Basım Tarihi: 2024
  • Doi Numarası: 10.1016/j.reprotox.2024.108661
  • Dergi Adı: REPRODUCTIVE TOXICOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chimica, Environment Index, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: 5-Fluorouracil, Endoplasmic reticulum stress, Gentisic acid, Inflammation, Nrf2, Ovotoxicity, Oxidative stress
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

5-Fluorouracil (5-FU) is the third most used chemotherapeutic in the world with its anticancer effect resulting from its potential to block DNA replication. Like other cytotoxic agents, 5-FU has side effects on healthy tissues, and the reproductive system is among the tissues most affected by these undesirable effects. Gentisic acid (GEA) is a secondary metabolite that is abundant in fruits, vegetables and spices and has antioxidant activity. This study was conducted to investigate the toxicity of 5-FU in rat ovarian tissue and to determine the therapeutic activity of GEA on ovotoxicity caused by 5-FU. The results showed that 5-FU caused histopathological findings by suppressing Nrf2 pathway and accordingly increasing oxidative stress, inflammation, endoplasmic reticulum stress and apoptosis. However, GEA treatments after 5-FU application ameliorated 5-FU-induced ovotoxicity dosedependently through activation of Nrf2 pathway. All these findings provided strong evidence supporting the hypothesis that GEA treatment may have therapeutic effects against 5-FU-induced ovarian damage. However, the beneficial effect of GEA use in eliminating ovarian damage in women after 5-FU chemotherapy should continue to be investigated with more detailed molecular studies.