Can ebselen prevent cisplatin-induced ovarian damage?
- 29 Downloads
The occurrence of ovarian damage is a major shortcoming in treating tumors with cisplatin (CP). The present study investigates the beneficial effects of ebselen—a seleno-organic compound with antioxidant and antiinflammatory properties—vis-à-vis CP-induced ovarian damage.
Twenty-eight adult female rats were divided into four study groups. Group 1 received no treatment. The rats in Groups 2, 3, and 4 were intraperitoneally administered CP (2 mg/kg/day) twice per week, for 5 weeks. Those in Group 2 received 0.3 ml saline (0.9% NaCl) intraperitoneally 60 min before each CP treatment, while those in Group 3 received 0.2 ml dimethyl sulfoxide (DMSO) and 0.3 ml saline intraperitoneally 60 min before each CP treatment. The rats in Group 4 were pretreated with an intraperitoneal injection of 15 mg/kg/day ebselen 60 min before each CP treatment. Ovarian tissue malondialdehyde (MDA), total nitric oxide (NOx), glutathione (GSH), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and catalase levels, as well as histopathological damage scores (HDSs) and serum antimullerian hormone (AMH) levels, were assessed.
Cu/Zn-SOD and GSH levels were significantly higher, and MDA and NOx levels significantly lower, in Group 4 than in Groups 2 and 3. Pretreatment with ebselen significantly improved serum AMH levels, relative to Groups 2 and 3. Additionally, HDS values were significantly lower in Group 4 than in Groups 2 and 3.
Our results from using an experimental rat model of CP chemotherapy suggest that ebselen use may ameliorate ovarian damage by preventing oxidative injury.
KeywordsAnti-mullerian hormone Cisplatin Ebselen Oxidative stress Ovary
This work was financially supported by the Research Fund of Istanbul Education and Research Hospital (Grant Number: 19.03.2015/64).
ZS was involved in management data analysis, intellectual idea, protocol development, data collection, writing and editing; HU was involved in data collection and writing; NB was involved in data collection and statistics; ME was involved in data collection and editing; BB was involved in data collection and management data analysis.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interests.
The presented study was approved by the animal local ethics committee of Bezmialem Vakif University. All procedures performed in studies involving animals were in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.
- 3.Yucebilgin MS, Terek MC, Ozsaran A, Akercan F, Zekioglu O, Isik E et al (2004) Effect of chemotherapy on primordial follicular reserve of rat: an animal model of premature ovarian failure and infertility. Aust N Z J Obstet Gynaecol 44:6–9. https://doi.org/10.1111/j.1479-828X.2004.00143.x CrossRefPubMedGoogle Scholar
- 7.Soylu Karapinar O, Pinar N, Özcan O, Atik Doğan E, Bayraktar S, Şahin H, Dolapçioğlu K (2017) The effect of dexpanthenol on experimentally induced ovarian ischaemia/reperfusion injury: a biochemical and histopathological evaluation. Arch Gynecol Obstet 295:777–784. https://doi.org/10.1007/s00404-017-4287-y CrossRefPubMedGoogle Scholar
- 19.Beutler E, Duran O, Kelly MB (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 51:882–888Google Scholar
- 20.Sun Y, Oberly LW, Ying LA (1998) Simple method for clinical assay of superoxide dismutase. Clin Chem 34:497–500Google Scholar
- 22.Witte AB, Anestal K, Jerremalm E, Ehrsson H, Arner ES (2005) Inhibition of thioredoxin reductase but not of glutathione reductase by the major classes of alkylating and platinum-containing anticancer compounds. Free Radic Biol Med 1:696–703. https://doi.org/10.1016/j.freeradbiomed.2005.04.025 CrossRefGoogle Scholar
- 29.Dhanarajan R, Abraham P, Isaac B (2006) Protective effect of ebselen, a selenoorganic drug, against gentamicin-induced renal damage in rats. Basic Clin Pharmacol Toxicol 99:267–272. https://doi.org/10.1111/j.1742-7843.2006.pto_474.x CrossRefPubMedGoogle Scholar
- 33.Akdemir A, Zeybek B, Akman L, Ergenoglu AM, Yeniel AO, Erbas O et al (2014) Granulocyte-colony stimulating factor decreases the extent of ovarian damage caused by cisplatin in an experimental rat model. J Gynecol Oncol 25:328–333. https://doi.org/10.3802/jgo.2014.25.4.328 CrossRefPubMedCentralPubMedGoogle Scholar