N-nitrosodiethylamine (NDEA) is an environmental mutagen and carcinogen compound that leads to cell damage by inducing oxidative stress. Tyrosol (Tyr) is a phenolic compound that decreases the production of reactive oxygen species and alleviates oxidative stress by influencing multiple cellular pathways. This study investigates the toxic effects of N-nitrosodiethylamine on rat ovaries and the protective role of Tyr. In this experimental study, 36 female rats were randomly divided into six groups: control; NDEA (200 mg/kg body weight, intraperitoneally) on the 4th day of study; Tyr (10 and 20 mg/kg body weight, gavage) for 7 consecutive days; and NDEA (200 mg/kg) + Tyr (10 and 20 mg/kg). After 48 h of treatment with the last dose of Tyr, the rats were sacrificed, and then blood samples were collected for histochemical and biochemical analysis, and ovariectomy was conducted for histopathological and immunohistochemical evaluation. The increase in malondialdehyde levels, along with a decrease in glutathione, suggests that NDEA induced oxidative stress in ovarian tissue. Histological examinations showed a reduction in germ cells, an increase in atretic follicles, and impaired oocyte maturation in rats exposed to NDEA. Decreased levels of estrogen and progesterone accompanied these changes. Moreover, NDEA-treated rats showed elevated caspase-3 immunoreactivity, indicating increased apoptosis in ovarian cells. Conversely, administering Tyr before and after NDEA exposure demonstrated a protective effect, significantly reducing oxidative damage and apoptosis, while preserving ovarian function, particularly at higher doses. These findings suggest that Tyr could be a potential protective agent against NDEA-induced ovarian toxicity due to its antioxidant and anti-apoptotic properties.
Maleki et al. (2026) studied this question.