Chemoprotective effect of ascorbic acid, α-tocopherol, and selenium on cyclophosphamide-induced toxicity in the rat ovarium

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Vol. 29; no. 5; pp. 777 - 784
• Main Authors: GÜRGEN, Seren Gülşen, ERDOGAN, Deniz, ELMAS, Ciğdem, KAPLANOGLU, Gülnur Take, OZER, Ciğdem
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.05.2013; Elsevier
• Subjects: alpha-Tocopherol - pharmacology; alpha-Tocopherol - therapeutic use; Animals; Antineoplastic Agents, Alkylating - toxicity; Antioxidants - metabolism; Antioxidants - pharmacology; Antioxidants - therapeutic use; Ascorbic acid; Ascorbic Acid - pharmacology; Ascorbic Acid - therapeutic use; Biological and medical sciences; Cyclophosphamide; Cyclophosphamide - toxicity; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; GDF-9; Glutathione - metabolism; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Growth Differentiation Factor 9 - metabolism; Oocytes - drug effects; Oocytes - metabolism; Ovarian Diseases - chemically induced; Ovarian Diseases - metabolism; Ovarian Diseases - pathology; Ovarian Diseases - prevention & control; Ovarium; Ovary - drug effects; Ovary - metabolism; Ovary - pathology; PCNA; Proliferating Cell Nuclear Antigen - metabolism; Rats; Rats, Wistar; Selenium; Selenium - pharmacology; Selenium - therapeutic use; Vertebrates: anatomy and physiology, studies on body, several organs or systems; α-Tocopherol; Cyclophosphamide; PCNA; Ascorbic acid; α-Tocopherol; Selenium; Ovarium; GDF-9; Rat; Toxicity; Rodentia; Vitamin; Antioxidant; Micronutrient; Vertebrata; Mammalia; Animal
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2012.11.004

Abstract Objective The aim of the study was to evaluate the protective efficacy of ascorbic acid, α-tocopherol, and selenium by measuring the glutathione (GSH) levels and proliferating cell nuclear antigen (PCNA) and growth differentiation factor-9 (GDF-9) expression in the ovarian tissues of rats treated with cyclophosphamide (CP) therapy. Methods Female Wistar rats were divided into 5 groups of 6 rats each: (I) control, (II) only CP, (III) CP + ascorbic acid, (IV) CP + α-tocopherol, and (V) CP + selenium. Immunohistochemical stainings and GSH protocol were then applied. Results Following CP administration, the rats exhibited significantly lower GDF-9 expression in oocytes and PCNA expression in granulosa cells of follicles in all stages of development ( P < 0.05). In CP + antioxidant groups (Groups III, IV, V), GDF-9 immunoreaction in oocytes and PCNA immunoreaction in granulosa cells of the developing follicles were found to show an increase towards the levels observed in the control group ( P < 0.05). Conclusions CP was found to cause remarkable degenerative effects in normal ovarian tissue, and we believe that this damage can be reduced and ovarian tissue can be spared from the toxic effects of CP by using antioxidants such as ascorbic acid, α-tocopherol, and selenium.