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Treatment of obesity-associated overactive bladder by the phosphodiesterase type-4 inhibitor roflumilast.
Int Urol Nephrol. 2017 Oct; 49(10):1723-1730.IU

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.

Authors+Show Affiliations

Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China.Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China. air-nick@hotmail.com.Department of Stomatology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China.Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China.Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China.Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28756610

Citation

Ding, Honglin, et al. "Treatment of Obesity-associated Overactive Bladder By the Phosphodiesterase Type-4 Inhibitor Roflumilast." International Urology and Nephrology, vol. 49, no. 10, 2017, pp. 1723-1730.
Ding H, Li N, He X, et al. Treatment of obesity-associated overactive bladder by the phosphodiesterase type-4 inhibitor roflumilast. Int Urol Nephrol. 2017;49(10):1723-1730.
Ding, H., Li, N., He, X., Liu, B., Dong, L., & Liu, Y. (2017). Treatment of obesity-associated overactive bladder by the phosphodiesterase type-4 inhibitor roflumilast. International Urology and Nephrology, 49(10), 1723-1730. https://doi.org/10.1007/s11255-017-1671-2
Ding H, et al. Treatment of Obesity-associated Overactive Bladder By the Phosphodiesterase Type-4 Inhibitor Roflumilast. Int Urol Nephrol. 2017;49(10):1723-1730. PubMed PMID: 28756610.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Treatment of obesity-associated overactive bladder by the phosphodiesterase type-4 inhibitor roflumilast. AU - Ding,Honglin, AU - Li,Ning, AU - He,Xiaoning, AU - Liu,Bing, AU - Dong,Liming, AU - Liu,Yili, Y1 - 2017/07/29/ PY - 2017/03/01/received PY - 2017/07/25/accepted PY - 2017/8/2/pubmed PY - 2018/8/2/medline PY - 2017/7/31/entrez KW - Detrusor overactivity KW - High-fat diet KW - Inflammatory KW - Obesity KW - Overactive bladder KW - Phosphodiesterase type-4 inhibitor SP - 1723 EP - 1730 JF - International urology and nephrology JO - Int Urol Nephrol VL - 49 IS - 10 N2 - 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. SN - 1573-2584 UR - https://www.unboundmedicine.com/medline/citation/28756610/Treatment_of_obesity_associated_overactive_bladder_by_the_phosphodiesterase_type_4_inhibitor_roflumilast_ L2 - https://doi.org/10.1007/s11255-017-1671-2 DB - PRIME DP - Unbound Medicine ER -