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 dose-dependently 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.
Keyphrases
- oxidative stress
- diabetic rats
- endoplasmic reticulum stress
- induced apoptosis
- ischemia reperfusion injury
- dna damage
- high glucose
- gene expression
- drug induced
- type diabetes
- squamous cell carcinoma
- polycystic ovary syndrome
- heat shock
- metabolic syndrome
- heat stress
- mass spectrometry
- risk assessment
- cell proliferation
- adipose tissue
- skeletal muscle
- single molecule
- heavy metals
- human health
- high resolution
- stress induced
- health risk
- anti inflammatory