Curcumin nanocrystals attenuate cyclophosphamide-induced testicular toxicity in mice

Toxicol Appl Pharmacol. 2021 Dec 15:433:115772. doi: 10.1016/j.taap.2021.115772. Epub 2021 Oct 27.

Abstract

The cancer therapy using cyclophosphamide (CP) has been associated with adverse effects on the testicular function that raises concerns about the future fertility potential among cancer survivors. Curcumin, a polyphenol, has shown to possess a plethora of biological functions including tissue protective effects. In the present study, we investigated the protective effects of curcumin nanocrystals (NC) in mitigation of CP-induced testicular toxicity. Healthy adult (8-10 week) and prepubertal (2 week) male Swiss albino mice were injected with a single dose of CP (200 mg/kg) intraperitoneally (i.p). NC (4 mg/kg, i.p.) was administered every alternate day, for 35 days in adult mice while, a single dose of NC was injected intraperitoneally to prepubertal mice 1 h prior to CP. Administration of multiple doses of NC ameliorated CP-induced testicular toxicity in adult mice, which was evident from the improved sperm functional competence, sperm chromatin condensation, seminiferous tubule architecture and decreased apoptosis in testicular cells. Further, administration of NC 1 h prior to CP in prepubertal mice modulated the expression of genes pertaining to proliferation, pluripotency, DNA damage and DNA repair in spermatogonial cells at 24 h after the treatment. Overall, these results suggest that NC could be a promising chemoprotective agent, which can have potential application in male fertility preservation.

Keywords: Chemoprotection; Chemotherapy; Curcumin nanocrystals; Germ cells; Spermatozoa; Testicular dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / toxicity*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Cell Proliferation / drug effects
  • Curcumin / chemistry
  • Curcumin / pharmacology*
  • Cyclophosphamide / toxicity*
  • DNA Damage / drug effects
  • Drug Compounding
  • Gene Expression Regulation
  • Infertility, Male / chemically induced
  • Infertility, Male / metabolism
  • Infertility, Male / pathology
  • Infertility, Male / prevention & control
  • Male
  • Mice
  • Nanoparticles*
  • Oxidative Stress / drug effects
  • Spermatogonia / drug effects*
  • Spermatogonia / metabolism
  • Spermatogonia / pathology
  • Testicular Diseases / chemically induced
  • Testicular Diseases / metabolism
  • Testicular Diseases / pathology
  • Testicular Diseases / prevention & control*
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / pathology
  • Time Factors

Substances

  • Antineoplastic Agents, Alkylating
  • Antioxidants
  • Cyclophosphamide
  • Curcumin