N-acetylcysteine mitigates oxidative damage to the ovary in D-galactose-induced ovarian failure in rabbits

Mol Biol Rep. 2024 Sep 23;51(1):1008. doi: 10.1007/s11033-024-09951-2.

Abstract

Background: Oxidative damage to the ovaries is the primary cause of impaired reproductive functions in female animals. This study aimed to investigate the protective role of N-Acetyl-L-cysteine (NAC) in reducing oxidative damage in the ovaries of female rabbits.

Methods and results: Female rabbit ovaries were treated in vitro with varying concentrations of D-galactose (D-gal): 0, 5, 10, and 15 mg/mL, and it was found that 10 mg/mL D-gal significantly disrupted follicular structures, causing disarray in granulosa cell arrangements and significantly reducing T-SOD and GSH levels (p < 0.01). Consequently, we selected 10 mg/mL D-gal to establish an ovarian failure model. These models were treated with multiple doses of NAC (0, 0.1, 0.3, 0.5 mg/mL). The results revealed that the disruption in granulosa cell arrangement caused by 10 mg/mL D-gal was effectively alleviated by 0.1 mg/mL NAC compared to the D-gal treatment group. Furthermore, 10 mg/mL D-gal significantly (p < 0.01) reduced GSH, T-SOD, and catalase (CAT) levels in the ovaries. However, 0.1 mg/mL NAC effectively (p < 0.01) suppressed these adverse effects. Moreover, the current results showed that 10 mg/mL D-gal alone significantly (p < 0.01) downregulated the expression of Nrf2, GPX, PRDX4, GSR, SOD1, and TAF4B, whereas 0.1 mg/mL NAC counteracted these suppressive effects (p < 0.01).

Conclusions: It could be concluded that NAC may delay ovarian failure by reducing D-gal-induced ovarian oxidative damage in female rabbit, suggested NAC could be a promising therapeutic agent for protecting against ovarian failure and potentially delaying ovarian failure in female rabbits.

Keywords: D-galactose; N-acetylcysteine; Ovarian failure; Oxidative damage.

MeSH terms

  • Acetylcysteine* / pharmacology
  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Catalase / metabolism
  • Disease Models, Animal
  • Female
  • Galactose* / adverse effects
  • Galactose* / pharmacology
  • Glutathione / metabolism
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism
  • Ovary* / drug effects
  • Ovary* / metabolism
  • Ovary* / pathology
  • Oxidative Stress* / drug effects
  • Primary Ovarian Insufficiency / chemically induced
  • Primary Ovarian Insufficiency / metabolism
  • Primary Ovarian Insufficiency / pathology
  • Rabbits
  • Superoxide Dismutase / metabolism

Substances

  • Acetylcysteine
  • Galactose
  • Antioxidants
  • Superoxide Dismutase
  • Glutathione
  • Catalase