Chemoprotective Effect of Plantago sempervirens Crantz Extract on Ovarian Structure and Folliculogenesis

Abstract

Alkylating agents such as cyclophosphamide (CPA) are commonly used in cytotoxic or immunosuppressive therapies for different types of diseases. One of the main secondary effects of such therapy is the reduction in follicular reserve, targeting the primordial follicles. The aim of this study was to investigate the antioxidant and protective effects of Plantago sempervirens extract on the follicular pool. The experiment was performed on Wistar female rats, for 21 days. They were divided into five groups according to the treatment they received (Control, CPA (200 mg/kg BW), P. sempervirens extract in three different doses—25/50/100 dw/mL ethanol extract (5 mL/kg BW)). The investigations regarded enzymatic and non-enzymatic nitro-oxidative stress, hormone levels (FSH and estrogen), TEM sections of the ovaries, and oestrus cycle monitorization. CPA strongly increased the oxidative stress (TOS—32.8 mmol H2O2/L; NO—68.60 μmol/L; OSI—6.82), alongside a depletion of FSH and a blockage of the oestrus cycle in the metestrus phase. The follicular pool was strongly depleted during CPA exposure, but FSH concentration and the TEM images of the cells revealed a significant improvement after treatment, as the dose increases (P3). Therefore, these findings reveal that P. sempervirens therapy could have a potential protective effect against CPA-induced acute damages in the ovaries, as well as maintaining a functional oestrus cycle.