Effect of hyaluronic acid on urine nerve growth factor in cyclophosphamide‐induced cystitis

Objectives: To investigate how hyaluronic acid (HA) affects nerve growth factor (NGF) production and bladder overactivity in a cyclophosphamide (CYP)‐induced cystitis rat model. Methods: Female Sprague–Dawley rats received three intermittent intraperitoneal injections of CYP (75 mg/kg) or saline. Before or after CYP injection, HA was given intravesically and urine NGF was checked with creatinine correction. Bladder function was evaluated by cystometrograms under Zoletil anesthesia. Furthermore, the effect of HA was counteracted with hyaluronidase (HYAL). Bladder structural change was compared among groups with trichrome stain. Results: The intercontraction interval (ICI) significantly decreased in CYP‐injected rats in comparison to the saline‐injected controls. In the CYP‐injected groups, bladder HA instillation significantly increased the ICI, but did not change the maximum voiding pressure in comparison to the saline instillation. NGF production significantly increased in CYP‐injected rats, but decreased significantly with HA treatment. Treatment with HA had a more significant effect on urine NGF and the use of HYAL would eliminate this effect. Specific staining showed mucosa swelling after CYP treatment. Little HA coating on bladder mucosa could be found in HA‐treated rats. Conclusions: Present findings raise the possibility that HA could be an effective treatment for CYP‐related bladder overactivity through the involvement of NGF signaling.