Sitagliptin protects male albino rats with testicular ischaemia/reperfusion damage: Modulation of VCAM-1 and VEGF-A

Andrologia. 2020 Mar;52(2):e13472. doi: 10.1111/and.13472. Epub 2019 Nov 26.

Abstract

Twisting of the spermatic cord is considered a popular problem in the urological field, which may lead to testicular necrosis and male infertility. Sitagliptin, a glucose-lowering agent, proved to have a vindicatory function in myocardial and renal ischaemia/reperfusion (I/R), but its role in testicular I/R has not yet been studied. The current work investigates its capability to recover the testicular I/R injury with shedding more light on the mechanism of its action. Four groups were used: sham, sham pretreated with sitagliptin, I/R and sitagliptin/I/R-pretreated groups. The outcomes proved that I/R significantly decreased the serum testosterone, with a major increase in oxidative, inflammatory and nitrosative stress, along with a reduction in testicular vascular endothelial growth factor-A level with marked germinal cell apoptosis. However, pretreatment with sitagliptin significantly reversed the profound testicular I/R damaging effects, on the basis of its antioxidant, anti-inflammatory and anti-apoptotic activities with the ability of recuperation of the testicular vascularity.

Keywords: apoptosis; inflammatory stress; sitagliptin; testicular ischaemia/reperfusion; vascular endothelial growth factor.

MeSH terms

  • Animals
  • Cholesterol / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Drug Evaluation, Preclinical
  • Male
  • Oxidative Stress / drug effects
  • Rats
  • Reperfusion Injury / blood
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Sitagliptin Phosphate / pharmacology
  • Sitagliptin Phosphate / therapeutic use*
  • Spermatogenesis / drug effects
  • Testicular Diseases / blood
  • Testicular Diseases / pathology
  • Testicular Diseases / prevention & control*
  • Testis / drug effects*
  • Testis / metabolism
  • Testis / pathology
  • Testosterone / blood
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Testosterone
  • Cholesterol
  • Sitagliptin Phosphate