Bladder urotoxicity pathophysiology induced by the oxazaphosphorine alkylating agents and its chemoprevention

The use of oxazaphosphorines (cyclophosphamide, ifosfamide) in the treatment of numerous neoplastic disorders is associated with their essential adverse effect in the form of hemorrhagic cystitis, which considerably limits the safety and efficacy of their pharmacotherapy. HC is a complex inflammatory response, induced by toxic oxazaphosphorines metabolite - acrolein with subsequent immunocompetetive cells activation and release of many proinflammatory agents. However, there are some chemoprotectant agents which help reduce the HC exacerbation. The article briefly discuses the mechanism of action of oxazaphosphorines, the pathophysiology of the hemorrhagic cystitis development and currently accepted chemopreventive agents, applied to the objective of urotoxicity amelioration. Moreover, the rationale for some phytopharmaceuticals administration as novel bladder protective compounds accompanying cyclophosphamide or ifosfamide therapy was also mentioned.