Protective effect of hydroxytyrosol in rats with ovarian toxicity caused by doxorubicin

Doxorubicin (Dox) is a chemotherapeutic agent widely used in the treatment of breast cancer, which is commonly observed in women of reproductive age, and is also known to cause ovarian toxicity. In this study, the potential effects of Hydroxytyrosol (HT) on ovarian toxicity were investigated. Twenty-eight female Sprague Dawley rats, aged 8–10 weeks and weighing 200–250 g, were used. The rats were divided into four groups: 1. Control group, 2. Dox group, 3. HT group, and 4. Dox+HT group. The Control group received 1 ml of physiological saline orally for 4 weeks; the Dox group was administered a single intraperitoneal dose of Dox at 10 mg/kg on the first day of the experiment; the HT group received HT orally at 4 ml/kg/day for 4 weeks; and the Dox+HT group received a single intraperitoneal dose of Dox at 10 mg/kg on the first day, followed by oral administration of HT at 4 ml/kg/day for 4 weeks. At the end of the 28-day experimental period, the ovaries were excised, and histopathological and immunohistochemical analyses were performed. All obtained data were statistically evaluated. Histochemical analyses revealed that Dox induced degenerative changes in the medulla and follicles of the ovarian tissue. In addition, it relatively increased the number of cystic follicles. Dox administration significantly reduced the numbers of primordial, secondary, and Graafian follicles compared with the control and other groups, while the number of atretic follicles was increased. In the Dox+HT group, only the number of atretic follicles showed a statistically significant reduction compared with the Dox group. Based on these findings, it was concluded that HT is a substance with a beneficial effect on Dox-induced ovarian toxicity. Keywords: Overtoxicity; Hydroxytyrosol; Doxorubicin; TRPC1.