Rosiglitazone treatment attenuates renal tissue inflammation generated by urinary tract obstruction

Shai Efrati, Sylvia Berman, Avraham Chachashvili, Natan Cohen, Yariv Siman-Tov, Zhan Averbukh, Joshua Weissgarten

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: Peroxisome proliferator-activated receptor (PPAR)-γ activation by rosiglitazone decreases manifestation of intrarenal inflammatory hallmarks. Inflammation significantly aggravates renal injury following urinary tract obstruction. The effect of rosiglitazone on renal inflammation following unilateral ureteral obstruction was investigated. Methods: Ninety-six Srague-Dawley rats were subjected to unilateral ureteral ligation, or to sham operation. Half of each group received rosiglitazone, 5 mg/kg bodyweight per day. The animals were killed and their kidneys allocated following 1 h, 24 h or 2 weeks, for pathological examination or for intrarenal transforming growth factor (TGF)-β, interleukin (IL)-4, IL-6, IL-10 and nitric oxide (NO) assessment by specific enzyme-linked immunosorbent assays. Apoptosis rates, extracellular matrix deposition, PPAR-γ, α-smooth muscle actin (α-SMA) expression and macrophage infiltration were assessed by specific immunohistological stainings. Results: PPAR-γ receptor expression was downregulated, and infiltration of macrophages decreased, in all rosiglitazone-treated kidneys. Rosiglitazone significantly decreased apoptosis, TGF-β, IL-6, α-SMA expression and NO availability in obstructed kidneys. Synthesis of IL-10 was unaltered, while IL-4 augmented by Rosiglitazone. Rosiglitazone also affected NO and IL-4 production in sham-operated controls. Conclusion: (i) Rosiglitazone attenuates profibrotic and pro-inflammatory responses in a rat model of ureteral obstruction-induced renal inflammation; (ii) rosiglitazone stimulates counteractive anti-inflammatory responses in the damaged kidneys; (iii) in part, rosiglitazone exerts comparable anti-inflammatory effects on obstructed kidneys and unobstructed healthy controls. Taken together, this ascertains the importance of the anti-inflammatory role of rosiglitazone treatment in amelioration of ureteral obstruction-induced renal damage.

Original languageEnglish
Pages (from-to)189-197
Number of pages9
JournalNephrology
Volume14
Issue number2
DOIs
StatePublished - Mar 2009

Keywords

  • Inflammation
  • Nitric oxide
  • Peroxisome proliferator-activated receptor
  • Rosiglitazone
  • Transforming growth factor-β
  • Ureteral obstruction

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