Alterations in bladder urothelial acetylcholine, ATP, prostaglandin E2 and inflammatory cytokines by the chemotherapeutic agent epirubicin — ASN Events
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Alterations in bladder urothelial acetylcholine, ATP, prostaglandin E2 and inflammatory cytokines by the chemotherapeutic agent epirubicin (#218)

Sung Hyun Kang 1 , Catherine McDermott 1 , Russ Chess-Williams 1
  1. Faculty of Health Sciences and Medicine, Bond University, Robina, Queensland, Australia

Epirubicin is a cytotoxic agent administered intravesically for the treatment of superficial bladder cancer.  During treatment the drug comes into close contact with the urothelium and post-treatment, patients may suffer urinary adverse effects.  The aim of this study was to assess the effects of epirubicin on the release of urothelial mediators and inflammatory cytokines to determine if they may play a role in the adverse effects associated with intravesical epirubicin treatment.

Immediately and 24hr following a 1 hour treatment of cultured UROtsa human urothelial cells with epirubicin, samples of incubation medium were prepared for analysis of basal and stretch-induced (using hypotonic solution) mediator release. Incubation medium was collected 24 hr after epirubicin pretreatment for analysis of inflammatory cytokines.

Immediately following epirubicin treatment, basal Ach release was significantly increased (2-fold, P<0.01) at 1mg/ml compared to the untreated controls and the Ach response to hypotonic stimulation was abolished (P<0.01). Both basal release and stretch-induced ATP release were significantly increased (2-fold, P<0.01) after 0.1mg/ml epirubicin.  In addition, basal PGE2 release was significantly increased (2-fold, P<0.01), but stretch-induced release was abolished (P<0.05) after 1mg/ml epirubicin. Twenty four hours after pretreatment, basal Ach release was significantly increased (P<0.05) and stretch-induced Ach release was reduced by 70% (P<0.01) by 0.01mg/ml epirubicin. Both basal and stretch-induced ATP release were significantly increased (5-fold, P<0.01 and 4-fold, P<0.01 respectively) by 0.01mg/ml epirubicin. In contrast, PGE2 release was unaffected by epirubicin at any concentration. In addition, interleukin-6 and -8 were significantly enhanced (66-fold, P<0.01 and 5-fold, P<0.01 respectively) 24 hours after epirubicin pretreatment (0.01mg/ml).

These findings indicate that inflammatory cytokines interleukin-6 and interleukin-8 are induced and urothelial mediator release is affected by treatment with epirubicin at clinically relevant concentrations and durations of treatment. These changes may play a role in the adverse effects observed in patients following intravesical epirubicin treatment.

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