Doxorubicin induces detrusor smooth muscle impairments through myosin dysregulation, leading to a risk of lower urinary tract dysfunction.

In this study, we tested the hypothesis that systemic doxorubicin administration also affects detrusor smooth muscle function in the urinary bladder, especially when administered at a young age. The effects on the detrusor smooth muscle and bladder function were assessed in BALB/cJ mice that received 6 weekly intravenous injections of doxorubicin (3mg/kg/wk) or saline for the control group. Systemic doxorubicin administration resulted in detrusor smooth muscle hypertrophy, increased voiding frequency and a significant attenuation of detrusor smooth muscle contractility followed by a slower relaxation compared to the control group. Gene expression analyses reveled that unlike doxorubicin-induced cardiotoxicity, the bladders from doxorubicin-administered animals showed no changes in oxidative stress markers, instead, downregulation of large conductance/big potassium (BK) channel and altered expression of myosin light chain kinase coincided with reduced myosin light chain phosphorylation. These results indicate that <italic>in vivo</italic> doxorubicin exposure caused detrusor smooth muscle dysfunction by dysregulation of molecules involved in the detrusor contractile-relaxation mechanisms. Collectively, our findings suggest that childhood cancer survivors treated with doxorubicin may be at increased risk of bladder dysfunction, and benefit from follow-up surveillance of bladder function. PMID: 31066574 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research