Chemotherapy-induced hemorrhagic cystitis: pathogenesis, pharmacological approaches and new insights

Chemotherapy-induced hemorrhagic cystitis (HC) remains a common and lifethreatening clinical complication, mainly due to the increasing usage of alkylating agents during conditioning regimen for hematopoietic cell transplantation. Currently, mesna and hyperhydration are the two more employed preventive measures. However, these prophylactic approaches have been proven not to be completely effective, since cystoscopic and histopathologic bladder damage are evidenced. Therefore, understanding the pathogenesis of HC must be the cornerstone for the development of novel therapeutic strategies. The purpose of this review is to examine the current knowledge regarding the pathogenesis of HC, describing the importance of transcription factors (nuclear factor kappaB), cytokines (tumor necrosis factor-α, interleukin-1β, -4, -6, and -8), enzymes (inducible nitric oxide synthase and cyclooxygenase-2), among other mediators, for the bladder injury. We also discuss the currently available animal models and future perspectives on the management of HC.