Effects of angiotensin II type 1 receptor blocker on albumin-induced cell damage in human renal proximal tubular epithelial cells.
OBJECTIVE
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-beta-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.


CONCLUSIONS
These observations suggest renal tubular cell-protective properties of ARBs related to decreased oxidative stress during proteinuria.
Takao
Toshihiro
T
Division of Community Medicine, Department of Community Nursing, Kochi Medical School, Nankoku, Japan. takaot@kochi-u.ac.jp
Horino
Taro
T
Kagawa
Toru
T
Matsumoto
Reiko
R
Inoue
Kousuke
K
Taguchi
Takafumi
T
Morita
Tatsuhito
T
Iwasaki
Yasumasa
Y
Hashimoto
Kozo
K
Terada
Yoshio
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000118:Acetylglucosaminidase / Q000378:metabolism; D000418:Albumins / Q000494:pharmacology; D000419:Albuminuria / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D000418:Albumins; D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D000080242:8-Hydroxy-2'-Deoxyguanosine; C437965:olmesartan; D019255:NADPH Oxidases; C086986:CYBA protein, human; D000118:Acetylglucosaminidase; D003849:Deoxyguanosine; D014633:Valine