Effects of ba-wei-die-huang-wan on cyclophosphamide-induced ongoing bladder overactivity and acidic atp solution-induced provoking of bladder overactivity
Wei-Chia Lee, Yao-Chi Chuang, Po-Hui Chiang
Divisions of Urology, Kaohsiung Chang Gung Memorial Hospital,
Chang Gung University
Purpose: To investigate effects of Ba-Wei-Die-Huang-Wan (BWDHW) on cyclophosphamide (CYP)-induced ongoing bladder overactivity and acidic adenosine triphosphate (ATP) solution-induced provoking of bladder overactivity.
Materials and Methods: Female Wistar rats were injected with CYP (100 mg/kg) or saline respectively. Rats were treated with BWDHW (90 mg/kg/day) or vehicle for five days. Both the metabolic cage study and cystometry were evaluated. Acidic ATP solution (5 mM, pH 3.3) was instilled to provoke bladder overactivity. Bladder mucosa and muscle proteins were assessed by Western blotting.
Results: As compared to the controls, the CYP group showed significantly decreased mean cystometric intercontractile interval and increased micturition frequency, whereas the CYP/BWDWH group did not. The CYP group had significant protein overexpression in mucosal M2, M3, P2X2, and P2X3 receptors as well as detrusor M2 and M3 receptors. However, the CYP/BWDWH group had insignificant changes from controls. In the provoking test, the control/BWDHW and CYP/BWDHW groups were less affected by acidic ATP stimulation of intercontractile interval changes than the control group. Compared to the control group, the control/BWDHW group showed significantly lower mucosal P2X3 protein expression and the CYP group showed significant mucosal TRPV1 protein upregulation after the provoking test.
Conclusions: BWDHW treatment can ameliorate CYP-induced ongoing bladder overactivity and suppress mucosal P2X2, P2X3, M2, and M3 receptor protein overexpression, as well as detrusor M2 and M3 receptor protein overexpression. BWDHW pretreatment can reduce acidic ATP solution-provoked bladder overactivity by preventing TRPV1 receptor overexpression in CYP-treated bladder mucosa and inhibiting P2X3 receptor overexpression in naïve bladder mucosa.