Can ebselen prevent cisplatin-induced ovarian damage?

Arch Gynecol Obstet. 2018 Jun;297(6):1549-1555. doi: 10.1007/s00404-018-4750-4. Epub 2018 Mar 29.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: Our results from using an experimental rat model of CP chemotherapy suggest that ebselen use may ameliorate ovarian damage by preventing oxidative injury.

Keywords: Anti-mullerian hormone; Cisplatin; Ebselen; Ovary; Oxidative stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Mullerian Hormone / blood*
  • Antioxidants / pharmacology*
  • Azoles / pharmacology*
  • Catalase / metabolism
  • Cisplatin / adverse effects*
  • Cisplatin / pharmacology
  • Female
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Malondialdehyde / metabolism
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide / metabolism
  • Organoselenium Compounds / pharmacology*
  • Ovary / drug effects*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Azoles
  • Neuroprotective Agents
  • Organoselenium Compounds
  • Nitric Oxide
  • ebselen
  • Malondialdehyde
  • Anti-Mullerian Hormone
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione
  • Cisplatin