Honglin Ding1,2, Peng Zhang3, Ning Li4, Yili Liu1, Ping Wang1. 1. Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China. 2. Department of Urology, Affiliated Hospital, Chifeng University, 42 Wangfu Street, Chifeng, Neimeng, China. 3. Department of General Surgery, Shenyang 242 Hospital, 3 Leshan Road, Shenyang, Liaoning, China. 4. Department of Urology, Fourth Affiliated Hospital, China Medical University, 4 Chongshan East Road, Shenyang, Liaoning, China. air-nick@hotmail.com.
Abstract
PURPOSE: To demonstrate that phosphodiesterase type 4 (PDE4) inhibitors could potentially treat diabetic bladder dysfunction (DBD) through modulation of the systemic inflammatory response. METHODS: In this 6-week study, 60 female Sprague-Dawley rats were divided into three groups: (i) vehicle-treated control rats; (ii) vehicle-treated streptozocin (STZ)-injected rats; and (iii) roflumilast-treated STZ-injected rats. Oral roflumilast (5 mg/kg/day) was administered during the last 4 weeks of STZ injection to induce diabetes in the test group. At 6 weeks, a urodynamic study was performed in each group. The expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β in detrusor smooth muscle (DSM) was analyzed using quantitative reverse transcription-polymerase chain reaction and Western blotting. RESULTS: A significant decrease in bodyweight and significant increases in bladder weight and blood glucose level were observed in the diabetic rats and were not ameliorated by roflumilast treatment. Cystometry showed the increased bladder capacity, voiding volume, residual urine volume, and voiding interval in the diabetic rats and the prevention of these changes by roflumilast. These changes were accompanied by significantly enhanced expression of NF-κB, TNF-α, IL-6, and IL-1β in DSM tissue from diabetic rats. Furthermore, roflumilast attenuated the expression of inflammatory factors in DSM tissue. CONCLUSIONS: Oral treatment with roflumilast in diabetic rats improves bladder function and inhibits the expression of inflammatory factors in DSM tissue, indicating that PDE4 is a potential therapeutic target for DBD.
PURPOSE: To demonstrate that phosphodiesterase type 4 (PDE4) inhibitors could potentially treat diabetic bladder dysfunction (DBD) through modulation of the systemic inflammatory response. METHODS: In this 6-week study, 60 female Sprague-Dawley rats were divided into three groups: (i) vehicle-treated control rats; (ii) vehicle-treated streptozocin (STZ)-injected rats; and (iii) roflumilast-treated STZ-injected rats. Oral roflumilast (5 mg/kg/day) was administered during the last 4 weeks of STZ injection to induce diabetes in the test group. At 6 weeks, a urodynamic study was performed in each group. The expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β in detrusor smooth muscle (DSM) was analyzed using quantitative reverse transcription-polymerase chain reaction and Western blotting. RESULTS: A significant decrease in bodyweight and significant increases in bladder weight and blood glucose level were observed in the diabeticrats and were not ameliorated by roflumilast treatment. Cystometry showed the increased bladder capacity, voiding volume, residual urine volume, and voiding interval in the diabeticrats and the prevention of these changes by roflumilast. These changes were accompanied by significantly enhanced expression of NF-κB, TNF-α, IL-6, and IL-1β in DSM tissue from diabeticrats. Furthermore, roflumilast attenuated the expression of inflammatory factors in DSM tissue. CONCLUSIONS: Oral treatment with roflumilast in diabeticrats improves bladder function and inhibits the expression of inflammatory factors in DSM tissue, indicating that PDE4 is a potential therapeutic target for DBD.
Entities:
Keywords:
Diabetes; Diabetic bladder dysfunction; Inflammatory; Phosphodiesterase type 4; Streptozocin
Authors: Shaojing Ye; Fei Ma; Dlovan F D Mahmood; Katherine L Meyer-Siegler; Raymond E Menard; David E Hunt; Lin Leng; Richard Bucala; Pedro L Vera Journal: PLoS One Date: 2021-08-23 Impact factor: 3.240