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

Nutrition. 2013 May;29(5):777-84. doi: 10.1016/j.nut.2012.11.004. Epub 2013 Feb 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / toxicity
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / pharmacology
  • Ascorbic Acid / therapeutic use*
  • Cyclophosphamide / toxicity*
  • Female
  • 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*
  • Ovary / drug effects
  • Ovary / metabolism
  • Ovary / pathology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Rats
  • Rats, Wistar
  • Selenium / pharmacology
  • Selenium / therapeutic use*
  • alpha-Tocopherol / pharmacology
  • alpha-Tocopherol / therapeutic use*

Substances

  • Antineoplastic Agents, Alkylating
  • Antioxidants
  • Growth Differentiation Factor 9
  • Proliferating Cell Nuclear Antigen
  • Cyclophosphamide
  • Glutathione
  • alpha-Tocopherol
  • Selenium
  • Ascorbic Acid