BACKGROUND/AIMS: 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. 2007 S. Karger AG, Basel
BACKGROUND/AIMS: 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. 2007 S. Karger AG, Basel
Authors: Gursev S Dhaunsi; Mariam H M Yousif; Saghir Akhtar; Mark C Chappell; Debra I Diz; Ibrahim F Benter Journal: Eur J Pharmacol Date: 2010-05-04 Impact factor: 4.432