Effects of Angiotensin II Type 1 Receptor Blocker on Albumin-Induced Cell Damage in Human Renal Proximal Tubular Epithelial Cells

Abstract

Background/Aims: Proteinuria is not merely a marker of chronic nephropathies, but may also be involved in the progression to end-stage renal failure. We investigated the effect of angiotensin II type 1 receptor blockers (ARBs) on albumin-induced cell damage in human renal proximal tubular epithelial cells (RPTEC). Methods: The N-acetyl-β- D-glucosaminidase (NAG) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in the medium after albumin treatment with ARBs were determined by commercially available kits. The levels of p22^phox protein in RPTEC were measured using Western blotting after albumin treatment with ARBs. Angiotensin II concentrations in cell media and cell lysates were assayed with a commercially available kit. Results: Human albumin (0.1–10 mg/ml) dose-dependently increased NAG release and olmesartan or valsartan (10^–9–10^–7 mol/l) showed a significant reduction on albumin (1 mg/ml)-induced NAG release in RPTEC. Albumin treatment (1 mg/ml) showed significant increases in p22^phox protein levels in RPTEC and ARBs significantly decreased albumin-induced p22^phox protein levels. Significant increases in 8-OHdG levels were observed in the albumin (1 mg/ml)-treated group and ARBs markedly reduced albumin-induced 8-OHdG levels in RPTEC. Human albumin dose-dependently increased angiotensin II concentrations in both cell media and lysates. Conclusion: These observations suggest renal tubular cell-protective properties of ARBs related to decreased oxidative stress during proteinuria.