(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.
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)-β, 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-β were significantly augmented, while NO was significantly decreased in kidneys remaining after contralateral nephrectomy. Rosiglitazone treatment abrogated augmented IL-6, A-II and TGF-β 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, repre- sented by augmented IL-6, A-II and TGF-β 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.
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