Hydrogen-rich saline attenuates chemotherapy-induced ovarian injury via regulation of oxidative stress

Abstract:

Hydrogen has been reported to exert a therapeutic effect in several diseases due to its antioxidative, antiinflam-matory and anti-apoptotic properties. The aim of the present study was to investigate whether hydrogen-rich saline treatment could attenuate ovarian damage induced by cisplatin. A total of 240 adult, virgin, female Sprague Dawley rats, weighing 180-220 g, were randomly divided into four groups (n=60 per group): Control (Con), control + hydrogen-rich saline (Con + H2), cisplatin-induced ovarian injury (OI) and cisplatin-induced ovarian injury + hydrogen-rich saline (OI + H2). Cisplatin was diluted in saline immediately before use. In the OI and OI + H2 groups, the rats were administered a dose of cisplatin on the 1st and 7th days. The rats in the Con + H2 and OI + H2 groups were intraperitoneally injected with hydrogen-rich saline (10ml/kg body weight) once a day over a 2-week period. On the 14th, 28th and 42nd days (T1, T2 and T3) after the cisplatin injection, femoral vein blood was collected. At the end of the experiment, ovarian homogenates were prepared, and the samples were used for estrogen (E2), follicle-stimulating hormone (FSH), superoxide dismutase (SOD), catalase (CAT) and malondial- dehyde (MDA) examination. In addition, rats (n=10 per group) were sacrificed for bilateral ovary removal; one was fixed in formalin for follicle-counting analysis, while the other was used for nuclear factor erythroid 2-related factor 2 (Nrf2) detection by western blotting. Hydrogen-rich saline attenuated the FSH release, elevated the level of E2, improved the development of follicles, and reduced the damage to the ovarian cortex at T1, T2 and T3 in the OI + H2 rats. Cisplatin induced oxidative stress by increasing the levels of oxidation products and attenuating the activity of antioxidant enzyme, which could be reversed by hydrogen-rich saline treatment. Furthermore, hydrogen-rich saline regulated the Nrf2 protein expression in rats with ovarian damage. In conclusion, hydrogen-rich saline exerts a protective effect against cisplatin-induced ovarian injury by reducing MDA and increasing SOD and CAT activity. Ovarian injury induced by chemotherapy involves the activation of Nrf2.