title: Preventive effect of phosphodiesterase 5 inhibitor tadalafil on experimental post-pyelonephritic renal injury in rats.
abstract: BACKGROUND
  To evaluate the effects of Tadalafil, a phosphodiesterase 5 enzyme inhibitor, on Escherichia coli-induced renal damage in an acute pyelonephritis (PN) rat model.
  
  
  METHODS
  Experimental PN was induced in 32 Wistar rats, and four groups were formed: group 1 (no treatment), group 2 (antibiotic), group 3 (Tadalafil), and group 4 (antibiotic + Tadalafil). Antibiotic was given on days 3 to 8, and Tadalafil was administered between days 0 and 28 of bacterial inoculation. Half of the rats were killed on the ninth day (early period) and histopathological parameters, immunohistochemical renal fibrosis markers, and oxidant/antioxidant system activities were evaluated. The rest of the rats were killed at the sixth week of the study and evaluated for histopathological parameters and renal fibrosis markers.
  
  
  RESULTS
  Inflammatory activity was significantly milder in rats treated with antibiotic + Tadalafil versus no treatment group both in the early and late periods. In the late period, interstitial fibrosis or tubular atrophy was lower in the antibiotic + Tadalafil group versus the no treatment and antibiotic groups, and in Tadalafil versus antibiotic group. Tadalafil administration significantly reduced renal malondialdehyde and nitric oxide levels and enhanced superoxide dismutase and catalase activities. In addition, circulating tumor necrosis factor α, interleukin 1β was greatly reduced in Tadalafil group versus the no treatment group.
  
  
  CONCLUSIONS
  We have provided the first evidence that phosphodiesterase 5 enzyme inhibitor Tadalafil ameliorates circulating inflammatory cytokines, reverses oxidant/antioxidant dysfunction and eventually possesses an overall protective effect on renal tissue from Escherichia coli-induced PN-related kidney injury. Phophodieterase 5 inhibitor might be a novel therapeutic target for PN.
authors.affiliation: Department of Surgical Nursing Centre, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Zhu
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Yong-zhen
authors.initials: YZ
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhai
authors.forename: Jian-ping
authors.initials: JP
authors.lastname: Che
authors.forename: Yang
authors.initials: Y
authors.lastname: Yan
authors.forename: Guang-chun
authors.initials: GC
authors.lastname: Wang
authors.forename: Jun-hua
authors.initials: JH
authors.lastname: Zheng
mesh_terms: D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002243:Carbolines / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D004927:Escherichia coli Infections / Q000150:complications; D007668:Kidney / Q000503:physiopathology; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D011704:Pyelonephritis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D000068581:Tadalafil; D016212:Transforming Growth Factor beta / Q000032:analysis
chemical_list: D002243:Carbolines; D016207:Cytokines; D058986:Phosphodiesterase 5 Inhibitors; D016212:Transforming Growth Factor beta; D000068581:Tadalafil
keywords: Phosphodiesterase 5; Pyelonephritis; Renal damage; Tadalafil