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

Abstract

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. This research was planned to explore the effect of Vinpo (10-30mg/kg, orally) administered 1 or 4h before inducing cystitis by CP injection (300mg/kg, i.p.) on the urinary bladder of mice. Administration of Vinpo 30mg/kg, 4h 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 (30mg/kg, 4h before CP injection) against CP-induced bladder inflammation. This proposes that Vinpo 30mg/kg may become a promising pharmacological drug to prevent urinary adverse effects in patients treated with chemotherapy using CP.