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Treatment of obesity-associated overactive bladder by the phosphodiesterase type-4 inhibitor roflumilast

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Abstract

Purpose

To prove that phosphodiesterase type-4 inhibitors could potentially treat obesity-associated overactive bladder through modulation of the systemic inflammatory response.

Methods

In this 12-week study, 90 female Sprague–Dawley rats were divided into three groups: (1) vehicle-treated normal diet (ND)-fed rats; (2) vehicle-treated high-fat diet (HFD)-fed rats; and (3) roflumilast-treated HFD-fed rats. Oral roflumilast (5 mg/kg/day) was administered during the last 4 weeks of HFD feeding in the test group. At 12 weeks, a urodynamic study was performed in ten rats of each group. Bladder tissue was extracted, the bladder mucosa was separated under microscopy, and bladder detrusor smooth muscle (DSM) expression of TNF-α, interleukin (IL)-6, IL-1β, and nuclear factor kappa B (NF-κB) were analyzed using Western blotting and quantitative reverse transcription-polymerase chain reaction (qRT-PCR).

Results

Bodyweights of the HFD-fed rats significantly increased and were not ameliorated by roflumilast treatment. Cystometry evidenced augmented frequency and non-void contractions in obese rats that were also prevented by roflumilast. These alterations were accompanied by a markedly increased expression of TNF-α, IL-6, IL-1β, and NF-κB in DSM of obese rats. Furthermore, roflumilast decreased expression of inflammatory factors in DSM.

Conclusions

Oral treatment with roflumilast in rats fed an HFD restores normal bladder function and downregulates expression of inflammatory factors in the bladder.

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Funding

This study was funded by a grant from LNCCC of LNCCC-D16-2015 to Ning Li.

Author information

Correspondence to Ning Li.

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Conflict of interest

All authors declare that they have no conflict of interests with regard to the work reported in this manuscript.

Ethical approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed.

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Ding, H., Li, N., He, X. et al. Treatment of obesity-associated overactive bladder by the phosphodiesterase type-4 inhibitor roflumilast. Int Urol Nephrol 49, 1723–1730 (2017). https://doi.org/10.1007/s11255-017-1671-2

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Keywords

  • Overactive bladder
  • Detrusor overactivity
  • High-fat diet
  • Obesity
  • Phosphodiesterase type-4 inhibitor
  • Inflammatory