Potential chemoprotective effect of melatonin in cyclophosphamide- and cisplatin-induced testicular damage in rats

Fertil Steril. 2009 Sep;92(3):1124-1132. doi: 10.1016/j.fertnstert.2008.07.1758. Epub 2008 Oct 1.

Abstract

Objective: To evaluate the effect of melatonin on cyclophosphamide (CP)- and cisplatin-induced testicular toxicity with use of sperm parameters and biochemical and histopathologic approaches.

Design: Experimental study.

Setting: Vakif Gureba Hospital, Istanbul, Turkey.

Animals: Six-week-old adult male Wistar albino rats (N = 48).

Intervention(s): Cyclophosphamide was administered to rats by gavage at a single dose of 100 mg/kg body weight, only once. Cisplatin was injected intraperitoneally at single doses of 7 mg/kg/d for five consecutive days. Melatonin was both administered separately and coadministered with CP and cisplatin intraperitoneally at a dose of 10 mg/kg body weight.

Main outcome measure(s): Body and testicular weight, epididymal sperm characteristics, plasma T, and histopathologic structure of the testicular tissue were determined. Malondialdehyde (MDA) and reduced glutathione (GSH) levels and glutathione peroxidase (GSH-Px) activity were assessed in testicular tissue.

Result(s): Body and testicular weight, epididymal sperm count, motility and morphology, plasma T levels, the activities of GSH-Px, and GSH levels were significantly decreased whereas the level of MDA was significantly increased in rats of the CP and cisplatin group. Melatonin treatment increased GSH levels and GSH-Px activity, decreased MDA level in testicular tissue, and increased plasma T level. Cyclophosphamide and cisplatin caused irregular seminiferous tubules, reduction of seminiferous epithelial layers, significant maturation arrest, and perivascular fibrosis. Melatonin significantly improved histopathologic changes.

Conclusion(s): Melatonin may prevent CP- and cisplatin-induced testicular damage.

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects*
  • Cisplatin / pharmacology
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Cyclophosphamide / pharmacology
  • Fibrosis
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Injections, Intraperitoneal
  • Lipid Peroxidation / drug effects
  • Male
  • Malondialdehyde / metabolism
  • Melatonin / administration & dosage
  • Melatonin / pharmacology*
  • Models, Animal
  • Rats
  • Rats, Wistar
  • Spermatogenesis / drug effects
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / pathology*
  • Testosterone / blood

Substances

  • Antioxidants
  • Testosterone
  • Malondialdehyde
  • Cyclophosphamide
  • Glutathione Peroxidase
  • Glutathione
  • Melatonin
  • Cisplatin