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Vanillic acid abrogates cisplatin-induced ovotoxicity through activating Nrf2 pathway
Ahmet Mentese1, Selim Demir2, Hatice Kucuk3
1Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey.
Tissue & Cell
|July 21, 2023
Summary
Vanillic acid (VA) protects against cisplatin-induced ovarian damage by reducing oxidative stress and inflammation. This study demonstrates VA
Area of Science:
- Reproductive toxicology
- Pharmacology
- Biochemistry
Background:
- Cisplatin (CDDP) is a vital chemotherapy drug but causes ovarian toxicity, limiting its use in women.
- Oxidative stress (OS) and inflammation are key mechanisms in cisplatin-induced ovotoxicity.
- Vanillic acid (VA), a natural compound, possesses potent antioxidant properties.
Purpose of the Study:
- To investigate the protective effects of vanillic acid (VA) against cisplatin (CDDP)-induced ovarian damage in a rat model for the first time.
- To elucidate the underlying mechanisms of VA's therapeutic action, focusing on oxidative stress, inflammation, endoplasmic reticulum stress (ERS), and apoptosis.
- To assess the impact of VA on reproductive hormone levels in the context of CDDP-induced ovotoxicity.
Main Methods:
- Ovarian toxicity was induced in female rats using a single dose of cisplatin (5 mg/kg).
- Rats were treated with vanillic acid (5 and 10 mg/kg) for three days.
- Biochemical markers of oxidative stress, inflammation, endoplasmic reticulum stress, and apoptosis were measured in ovarian tissue; reproductive hormones were quantified in serum.
Main Results:
- Cisplatin administration led to increased ovarian damage, characterized by elevated OS, inflammation, ERS, apoptosis, and inhibition of the Nrf2 pathway.
- Vanillic acid treatment dose-dependently reversed these cisplatin-induced changes, mitigating ovarian damage.
- VA treatment activated the Nrf2 pathway, suggesting its crucial role in VA's protective effects. Histopathological analysis confirmed the biochemical findings.
Conclusions:
- Vanillic acid demonstrates significant therapeutic potential in preventing and treating cisplatin-induced ovarian damage.
- VA's protective effects are mediated through its antioxidant properties and activation of the Nrf2 pathway.
- VA is a promising candidate for further development as a protective agent against chemotherapy-induced reproductive toxicity.
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