Ameliorative effect of nerolidol on cyclophosphamide-induced gonadal toxicity in Swiss Albino mice: Biochemical-, histological- and immunohistochemical-based evidences

Andrologia. 2020 May;52(4):e13535. doi: 10.1111/and.13535. Epub 2020 Feb 12.

Abstract

Cyclophosphamide (CP) is commonly used as antineoplastic and immunosuppressant drug with noticeable gonadotoxic profile. Nerolidol (NER) is a sesquiterpene with potent antioxidant and anti-inflammatory properties. Thus, the present study was designed to explore its possible gonadal protective potential against cyclophosphamide-induced testicular, epididymal, seminal and spermatozoal toxicities. Animals were divided into five groups: control (normal saline for 14 days), treatment group (NER 200 and 400 mg/kg, p.o) for 14 days along with a single dose of cyclophosphamide (200 mg/kg, i.p) on 7th day, toxic and Per se groups (cyclophosphamide 200 mg/kg i.p) on 7th day and NER 400 mg/kg for 14 days respectively. Animals were sacrificed on the 15 day, and body weight, weight of reproductive organs, testosterone level, sperm count, biochemical parameters, histopathological and immunohistochemical studies were performed in the testes, epididymis and in the serum. CP administration induced oxidative stress, nitrative stress, inflammation, reduced testosterone level, sperm count, increased expression of MPO and caused histological aberrations in the testes, epididymis and seminal vesicles. CP caused reduced sperm count, sperm motility and testosterone level which got reversed upon treatment with nerolidol in a dose-dependent manner. Nerolidol thus acted as a gonadoprotective molecule and prevented the gonadotoxicity of CP.

Keywords: adjuvant therapy; chemotherapy; myeloperoxidase; testicular inflammation; testosterone.

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Cyclophosphamide / adverse effects*
  • Drug Evaluation, Preclinical
  • Epididymis / drug effects
  • Epididymis / metabolism
  • Genital Diseases, Male / chemically induced
  • Genital Diseases, Male / prevention & control*
  • Male
  • Mice
  • Oxidative Stress / drug effects
  • Peroxidase / metabolism
  • Sesquiterpenes / pharmacology
  • Sesquiterpenes / therapeutic use*
  • Testis / drug effects*
  • Testis / metabolism
  • Testosterone / blood
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antineoplastic Agents, Alkylating
  • Sesquiterpenes
  • Tumor Necrosis Factor-alpha
  • Testosterone
  • Cyclophosphamide
  • Peroxidase
  • nerolidol