Protective Effect of Glutathione Administration on Ovarian Function in Female Rats with Cyclophosphamide-Induced Ovarian Damage

Ebru Tansu Yurttancikmaz; Pinar Ozcan; Fatma Basak Tanoglu; Olgu Enis Tok; Hikmet Tunc Timur; Caglar Cetin

doi:10.1159/000536055

Protective Effect of Glutathione Administration on Ovarian Function in Female Rats with Cyclophosphamide-Induced Ovarian Damage

Gynecol Obstet Invest. 2024;89(2):120-130. doi: 10.1159/000536055. Epub 2024 Jan 22.

Authors

Ebru Tansu Yurttancikmaz¹, Pinar Ozcan¹, Fatma Basak Tanoglu², Olgu Enis Tok³, Hikmet Tunc Timur⁴, Caglar Cetin¹

Affiliations

¹ Department of Obstetrics and Gynaecology, Bezmialem University School of Medicine, Istanbul, Turkey.
² Obstetrics and Gynaecology Clinic, Caldiran State Hospital, Turkish Ministry of Health, Van, Turkey.
³ Department of Histology and Embryology, School of Medicine and Research Institute for Health Sciences and Technologies, Istanbul Medipol University, Istanbul, Turkey.
⁴ Department of Obstetrics and Gynaecology, Dokuz Eylul University School of Medicine, Izmir, Turkey.

Abstract

Objectives: We investigated the potential of glutathione to protect ovarian function in rats exposed to cyclophosphamide by measuring serum anti-Mullerian hormone (AMH) levels, follicle counts, and related parameters.

Design: Forty-two adult female Sprague-Dawley rats were randomly divided into six groups and treated with various combinations of cyclophosphamide, glutathione, and sodium chloride. On day 21, the rats were anesthetized, and their ovaries were removed for examination.

Participants/materials, setting, methods: Histopathological examination, serum AMH concentrations, follicle counts, AMH-positive staining of follicle percentages were analyzed. Statistical analysis was performed using a one-way analysis of variance and Tukey's test, with significance set at p < 0.05. Secondary measures encompassed histopathological examination and percentages of AMH-positive staining of follicles.

Results: Significant differences were observed in follicle counts, AMH-positive follicle parameters, and serum AMH concentrations among the six groups. Group 2 (treated with cyclophosphamide) had the lowest primordial, primary, secondary, and antral follicle counts and the highest atretic count. Group 6, treated with cyclophosphamide and 200 mg/kg glutathione, showed improved follicle counts compared to those in group 2. Reducing the glutathione dose to 100 mg/kg was ineffective.

Limitations: This was an experimental animal investigation with a comparatively modest sample size. Experimental studies should be conducted to determine the optimal dosage and duration of glutathione therapy. Information gathered from an experimental animal model may not yield precisely similar outcomes in humans; therefore, additional investigations are necessary to examine the impact of glutathione on women experiencing POI.

Conclusions: The anti-oxidative protective effect of directly administered glutathione was demonstrated for the first time. Low-dose glutathione was ineffective, whereas a high dose yielded significant ovarian protection against cyclophosphamide. Our findings provide valuable insights for supplementing clinical trials on the protective effects of glutathione against ovarian damage.

Keywords: Anti-Mullerian hormone; Antioxidants; Cyclophosphamide; Glutathione; Primary ovarian insufficiency.

MeSH terms

Adult
Animals
Anti-Mullerian Hormone
Cyclophosphamide / adverse effects
Female
Glutathione / pharmacology
Humans
Ovarian Follicle*
Ovary*
Rats
Rats, Sprague-Dawley

Substances

Cyclophosphamide
Anti-Mullerian Hormone
Glutathione

Grants and funding

The funding for this study was provided by the Scientific Projects Unit of Bezmialem University (Project No. 20220203E). The funding source had no involvement in study design, in the collection of data, in the writing of the report, or in the decision to submit the article for publication.