title: Rosiglitazone treatment attenuates expression of inflammatory hallmarks in the remaining kidney following contralateral nephrectomy.
abstract: OBJECTIVE
  Following kidney donation, living kidney donors have been reported to develop anemia and pronounced inflammation. Therapeutic strategies for ameliorating unilateral nephrectomy-induced inflammation would be beneficiary for the living donors. We applied rosiglitazone to attenuate inflammatory processes ongoing within the remaining kidney following contralateral nephrectomy.
  
  
  METHODS
  20 Sprague-Dawley rats were subjected to left unilateral nephrectomy and 20 others to sham operation. Half of each group was treated for 2 weeks with rosiglitazone (5 mg/kg body weight). After sacrifice, intrarenal transforming growth factor (TGF)-beta, angiotensin-II (A-II), interleukin (IL)-6, IL-10, IL-4 and nitric oxide (NO) were assessed, and histologic sections stained to assess the inflammatory cell infiltration. Renal function was evaluated by creatinine, urea, cystatin C measurements.
  
  
  RESULTS
  Intrarenal IL-6, A-II and TGF-beta were significantly augmented, while NO was significantly decreased in kidneys remaining after contralateral nephrectomy. Rosiglitazone treatment abrogated augmented IL-6, A-II and TGF-beta synthesis and restored intrarenal NO availability in the remaining kidneys. Rosiglitazone also augmented anti-inflammatory IL-4 cytokine synthesis, while IL-10 production, leukocyte infiltration and renal function parameters remained unchanged.
  
  
  CONCLUSIONS
  Rosiglitazone treatment attenuates the proinflammatory responses, represented by augmented IL-6, A-II and TGF-beta production, developing in the remaining kidney following contralateral nephrectomy. In addition, by stimulating IL-4 synthesis and restoring NO availability, rosiglitazone treatment initiates counteractive anti-inflammatory responses in the remaining kidney.
authors.affiliation: Nephrology Division, Assaf Harofeh Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Zerifin, Israel. efratishai@013.net
authors.forename: Shai
authors.initials: S
authors.lastname: Efrati
authors.forename: Sylvia
authors.initials: S
authors.lastname: Berman
authors.forename: Avraham
authors.initials: A
authors.lastname: Chachashvili
authors.forename: Natan
authors.initials: N
authors.lastname: Cohen
authors.forename: Zhan
authors.initials: Z
authors.lastname: Averbukh
authors.forename: Joshua
authors.initials: J
authors.lastname: Weissgarten
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001795:Blood Pressure Determination; D016207:Cytokines / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D007668:Kidney; D016030:Kidney Transplantation / Q000379:methods*; D019520:Living Donors; D008297:Male; D009392:Nephrectomy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone