Influence of the periprostatic adipose tissue in obesity-associated mouse urethral dysfunction and oxidative stress: Effect of resveratrol treatment

Autor(es)

Alexandre, Eduardo C. ^[1] ; Calmasini, Fabiano B. ^[1] ; Sponton, Amanda C. da S. ^[2] ; de Oliveira, Mariana G. ^[1] ; Andre, Diana M. ^[1] ; Silva, Fabio H. ^[3] ; Debin, Maria Andreia ^[1] ; Monica, Fabiola Z. ^[1] ; Antunes, Edson ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Fac Med Sci, Dept Pharmacol, Alexander Flemming St, 40 Fundos, BR-13084971 Campinas, SP - Brazil

^[2] Univ Campinas Unicamp, Inst Biol, Dept Struct & Funct Biol, BR-13083862 Campinas, SP - Brazil

^[3] Univ Campinas UNICAMP, Hematol & Hemotherapy Ctr, BR-13083878 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 836, p. 25-33, OCT 5 2018.
• Citações Web of Science: 0

Resumo

Obese mice display overactive bladder (OAB) associated with impaired urethra smooth muscle (USM) function. In this study, we evaluated the role of the adipose tissue surrounding the urethra and prostate in obese mice (here referred as periprostatic adipose tissue; PPAT) to the USM dysfunction. Male C57BL6/JUnib mice fed with either a standard-chow or high-fat diet to induce obesity were used. In PPAT, histological analysis, and qPCR analysis for gp91phox, tumor necrosis factor-alpha (TNF-alpha) and superoxide dismutase (SOD) were conducted. In USM, concentration-response curves to contractile and relaxing agents, as well as measurements of reactive-oxygen species and nitric oxide (NO) levels were performed. The higher PPAT area in obese mice was accompanied by augmented gp91phox (NOX2) and TNF-alpha expressions, together with decreased SOD1 expression. In USM of obese group, the contractile responses to phenylephrine and vasopressin were increased, whereas the relaxations induced with glyceryl trinitrate were reduced. The reactive-oxygen species and NO levels in USM of obese mice were increased and decreased, respectively. A higher SOD expression was also detected in obese group whilst no changes in the gp91phox levels were observed. We next evaluated the effects of the antioxidant resveratrol (100 mg/kg/day, two-weeks, PO) in the functional alterations and NO levels of obese mice. Resveratrol treatment in obese mice reversed both the functional USM dysfunction and the reduced NO production. Our data show that PPAT exerts a local inflammatory response and increases oxidative stress that lead to urethral dysfunction. Resveratrol could be an auxiliary option to prevent obesity-associated urethral dysfunction. (AU)

• Processo FAPESP: 08/57906-3 - Instituto Nacional de Fotônica Aplicada à Biologia Celular - INFABIC
• Beneficiário: Hernandes Faustino de Carvalho
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/15175-1 - Modulação da guanilato ciclase solúvel e dos níveis intracelulares de nucleotídeos cíclicos em órgãos do trato urinário inferior e próstata
• Beneficiário: Edson Antunes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/04556-4 - Envelhecimento e hiperplasia prostática: avaliação de alterações funcionais e moleculares em uretra prostática de ratos
• Beneficiário: Eduardo Costa Alexandre
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/02196-2 - Papel do estresse oxidativo e degradação da guanilil ciclase solúvel na disfunção miccional em camundongos obesos resistentes à insulina
• Beneficiário: Eduardo Costa Alexandre
• Modalidade de apoio: Bolsas no Brasil - Doutorado