Melatonin prevents and ameliorates lead-induced gonadotoxicity through antioxidative and hormonal mechanisms

Toxicol Ind Health. 2018 Sep;34(9):596-608. doi: 10.1177/0748233718773508. Epub 2018 May 15.

Abstract

We investigated the effects of melatonin on sperm parameters and some biochemical markers in lead-exposed male Wistar rats. Lead (50 mg/kg bw/day) and/or melatonin (4 mg/kg or 10 mg/kg bw/day) was administered for 4 weeks, while 2-week lead exposure was preceded by or followed by 2-week treatment with both doses of melatonin in other groups. Lead reduced glutathione, catalase, adjusted testes weight, semen parameters but did not change malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase, and total antioxidant capacity. Though independent of prolactin, lead-induced gonadotoxicity was both centrally and peripherally mediated, as it reduced gonadotropin-releasing hormone and testosterone levels, while gonadotropin levels did not change significantly probably due to negative feedback by elevated estradiol. However, pre-, simultaneous, or posttreatment of lead-exposed rats with melatonin reduced MDA, SOD, and estradiol but dose-dependently increased other parameters. Conclusively, lead causes male gonadotoxicity through oxidative stress and endocrine mechanisms, and these could be dose-dependently prevented and ameliorated by melatonin.

Keywords: Gonadotoxicity; lead; melatonin; oxidative stress; reproductive hormone; sperm.

MeSH terms

  • Animals
  • Antioxidants / analysis
  • Antioxidants / pharmacology*
  • Body Weight / drug effects
  • Gonadotropin-Releasing Hormone / blood
  • Gonadotropins, Pituitary / blood*
  • Lead / toxicity*
  • Male
  • Melatonin / pharmacology*
  • Oxidative Stress / drug effects*
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Spermatozoa / drug effects
  • Testis / drug effects

Substances

  • Antioxidants
  • Gonadotropins, Pituitary
  • Lead
  • Gonadotropin-Releasing Hormone
  • Melatonin