N-acetylcysteine ameliorates 5-fluorouracil-induced ovarian injury in rats

Abstract

Objective: Although 5-fluorouracil (5-FU) is one of the most commonly used chemotherapeutics worldwide, it has been shown that 5-FU administration can cause reproductive toxicity in recent years. N-acetylcysteine (NAC) is the precursor of glutathione, the most important endogenous antioxidant molecule and is known for its effective antioxidant and anti-inflammatory properties. Although NAC is one of the most studied antioxidant molecules, its curative effect against ovarian damage caused by 5-FU has not been demonstrated to date. It was therefore aimed to investigate whether NAC is therapeutic against 5-FU-induced ovotoxicity in this study for the first time.Methods: Rats were first exposed to a single dose of 5-FU (100 mg/kg) and then treated with NAC (10 and 20 mg/kg) for three days. The oxidative stress, inflammation and apoptosis markers in ovarian tissues were also determined using spectrophotometric methods. Ovarian tissues were also evaluated histologically.Results: It was revealed that the levels of oxidative stress, inflammation and apoptosis biomarkers in ovarian tissue increased by 5-FU administration (p<.005). Treatments with NAC significantly restored these damages dose-dependently (p<.005). Moreover, these biochemical findings were confirmed by histological examination.Conclusion: NAC can be considered as a potential therapeutic molecule against 5-FU-induced reproductive toxicity, as it can abolish the ovarian toxicity caused by 5-FU by reducing oxidative stress, inflammation and apoptosis.