Possible Protective Effects of Curcumin via Modulating of Androgen Receptor (AR) and Oct2 Gene Alterations in Cisplatin-Induced Testicular Toxicity in Rat

Endocr Metab Immune Disord Drug Targets. 2021;21(3):458-463. doi: 10.2174/1871530320666200511073302.

Abstract

Background: Cisplatin is a chemotherapeutic drug used to treat testicular cancer that induces testicular toxicity. This study aimed to investigate the possible role of androgens, androgen receptor, and organic cation transporter 2 (OCT2) in the protective effects of curcumin on cisplatininduced testicular toxicity.

Methods: Thirty male Wistar rats were divided into five groups: 1- control (normal saline, 0.5 ml ip, daily for 10 consecutive days); 2- cisplatin (10 mg/kg ip, single dose at the first day); 3- cisplatin + curcumin (10 mg/kg ip, dissolved in 5% DMSO, daily for 10 consecutive days); 4- cisplatin + vehicle (DMSO 5%, 0.3 ml ip); and 5- curcumin (10 mg/kg ip). At the end of the study, a blood sample was obtained for testosterone measurement. The left testis was kept at -80. to measure androgen receptor (AR) and type 2 organic cation transporter (OCT2) gene expression and the right testis were kept in 10% formalin for histological analysis.

Results: Cisplatin significantly decreased serum testosterone, declined testis AR gene expression, and increased OCT2 gene expression in testis (p<0.01). Curcumin treatment significantly prevented these alterations in testosterone and gene expressions (p<0.01). Moreover, curcumin significantly reversed the cisplatin-induced kidney tissue injury and increased spermatid and spermatozoa.

Conclusion: It is concluded that the ameliorative effect of curcumin in cisplatin-induced reproductive disorders was due to the modulation of testosterone and androgen receptors.

Keywords: Cisplatin; OCT2 gene; androgen receptors; curcumin; organic cation transporter; testis.

MeSH terms

  • Animals
  • Cisplatin
  • Curcumin / pharmacology*
  • Disease Models, Animal
  • Male
  • Organic Cation Transporter 2 / genetics
  • Organic Cation Transporter 2 / metabolism*
  • Protective Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Signal Transduction
  • Testicular Diseases / chemically induced
  • Testicular Diseases / metabolism
  • Testicular Diseases / pathology
  • Testicular Diseases / prevention & control*
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / pathology
  • Testosterone / blood

Substances

  • Organic Cation Transporter 2
  • Protective Agents
  • Receptors, Androgen
  • Slc22a2 protein, rat
  • Testosterone
  • Curcumin
  • Cisplatin