Phosphodiesterase1 inhibitor "Vinpocetine" ameliorates the inflammation, apoptosis and oxidative stress induced by cyclophosphamide in urinary bladder: an experimental study

Int Urol Nephrol. 2023 Jan;55(1):129-139. doi: 10.1007/s11255-022-03246-w. Epub 2022 Jul 11.

Abstract

Background: Hemorrhagic cystitis often develops in patients treated with cyclophosphamide (CP). Vincamine (vinca alkaloid) is the source of the synthetic derivative vinpocetine (Vinpo). Worldwide, Vinpo is used as a cerebroprotective drug. As it has anti-oxidant, anti-thrombotic and anti-inflammatory effects but the power of Vinpo to prevent CP induced cystitis has not been studied.

Aim of study: This research was planned to explore the effect of Vinpo (10-30 mg/kg, orally) administered 1 or 4 h before inducing cystitis by CP injection (300 mg/kg, i.p.) on the urinary bladder of mice.

Results: Administration of Vinpo 30 mg/kg, 4 h before CP injection ameliorated inflammatory markers. It reduced inducible nitric oxide synthase (iNOS), tumor necrosis factor- α (TNF-α), and BCL2 Associated X (Bax) expression in the bladder and increased the total antioxidant capacity level. Histological examination of the bladder has further supported these results. The present study suggests a protective effect of Vinpo (30 mg/kg, 4 h before CP injection) against CP-induced bladder inflammation.

Conclusion: This proposes that Vinpo 30 mg/kg may become a promising pharmacological drug to prevent urinary adverse effects in patients treated with chemotherapy using CP.

Keywords: Cyclophosphamide; Cystitis; Vinpocetine.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Apoptosis
  • Cyclophosphamide / adverse effects
  • Cystitis* / chemically induced
  • Cystitis* / drug therapy
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Mice
  • Oxidative Stress
  • Urinary Bladder / pathology
  • Vinca Alkaloids* / pharmacology
  • Vinca Alkaloids* / therapeutic use

Substances

  • Cyclophosphamide
  • Antioxidants
  • Vinca Alkaloids