Extract of Actaea racemosa Protects Mice Ovarian Follicles Against Doxorubicin-induced Toxicity

Abstract

Background: Given the cytotoxicity of chemotherapy drugs used in cancer treatment, there is a need to develop alternative agents to protect female fertility. This study investigated the effect of Actaea racemosa (A. racemosa) extract on mice ovarian cells and the damage caused by doxorubicin (DOX) to the mice ovaries. Methods: We evaluated the effects of A. racemosa extract on mice ovaries (n=42) after DOX treatment. The mice were pre-treated with saline solution (controls) or with 0.5 or 5 mg/kg A. Racemosa extract. Afterward, during a period of 10 days, they were treated daily with one of the six protocols: (i) saline solution (control), (ii) 10 mg/kg DOX, (iii) 0.5 mg/kg A. racemosa extract, (iv) both DOX and 5 mg/kg A. racemosa extract, (v) A. racemosa extract (5 mg/kg), and (vi) both DOX and 0.5 mg/kg A. racemosa extract. At the end of these treatments, the ovaries were fixed for histopathological examinations. Ovarian follicular morphology, stromal cell density, collagen fibers, and TNF-α expression were evaluated. Some ovaries were fixed for transmission electron microscopy or stored at -80oC to study the mRNA expression for Caspase-3 and TNF-α. Results: The Mice treated with A. racemosa extract had reduced follicular degeneration and cell death after exposure to DOX. Ovaries of mice treated with 0.5 mg/kg A. racemosa extract had granulosa cells and oocytes with preserved ultrastructure, decreased immunostaining for TNF-α, and reduced Caspase-3 mRNA. Conclusion: The A. racemosa extract supported follicular survival and protected the ovarian follicles and stromal cells against DOX-induced cytotoxicity.