PMID- 23052181
OWN - NLM
STAT- MEDLINE
DCOM- 20130423
LR  - 20121113
IS  - 1423-0313 (Electronic)
IS  - 0031-7012 (Linking)
VI  - 90
IP  - 5-6
DP  - 2012
TI  - Angiotensin II receptor blocker improves tumor necrosis factor-alpha-induced 
      cytotoxicity via antioxidative effect in human glomerular endothelial cells.
PG  - 324-31
LID - 10.1159/000343244 [doi]
AB  - BACKGROUND/AIMS: Tumor necrosis factor-alpha (TNF-alpha) is known to involve the 
      progression of renal dysfunction through its cytotoxicity and proinflammatory 
      effects such as the induction of intercellular adhesion molecule (ICAM)-1 
      expression in vascular endothelial cells (ECs). Olmesartan, one of the 
      angiotensin II type 1 receptor blockers (ARBs), has been reported to show 
      protective effects on injured ECs by some causal factors of renal disorder other 
      than angiotensin II. However, the effects of olmesartan on TNF-alpha-induced 
      glomerular EC damage have not been investigated. In the present study, we 
      investigated the effects of RNH-6270, an active metabolite of olmesartan, on 
      TNF-alpha-induced human glomerular EC (HGEC) damage to clarify the renoprotective 
      mechanisms of ARBs. METHODS: Cultured HGECs were stimulated by TNF-alpha, and then 
      cell viability and cytotoxicity were measured by MTT assay and lactate 
      dehydrogenase release assay, respectively. TNF-alpha-induced oxidative stress was 
      estimated by dihydroethidium assay and lucigenin chemiluminescence assay. ICAM-1 
      expression and the phosphorylations of mitogen-activated protein kinases were 
      measured using Western blotting assay. RESULTS: RNH-6270 suppressed cell death 
      and the increase in ICAM-1 expression induced by TNF-alpha via the inhibition of 
      reactive oxygen species in HGECs. CONCLUSION: Our findings suggested that 
      olmesartan might have protective effects against TNF-alpha-induced glomerular EC 
      dysfunction.
CI  - Copyright (c) 2012 S. Karger AG, Basel.
FAU - Izawa-Ishizawa, Yuki
AU  - Izawa-Ishizawa Y
AD  - Department of Pharmacology, The University of Tokushima Graduate School, 
      Tokushima, Japan.
FAU - Ishizawa, Keisuke
AU  - Ishizawa K
FAU - Sakurada, Takumi
AU  - Sakurada T
FAU - Imanishi, Masaki
AU  - Imanishi M
FAU - Miyamoto, Licht
AU  - Miyamoto L
FAU - Fujii, Shoko
AU  - Fujii S
FAU - Taira, Hironori
AU  - Taira H
FAU - Kihira, Yoshitaka
AU  - Kihira Y
FAU - Ikeda, Yasumasa
AU  - Ikeda Y
FAU - Hamano, Shuichi
AU  - Hamano S
FAU - Tomita, Shuhei
AU  - Tomita S
FAU - Tsuchiya, Koichiro
AU  - Tsuchiya K
FAU - Tamaki, Toshiaki
AU  - Tamaki T
LA  - eng
PT  - Journal Article
DEP - 20121009
PL  - Switzerland
TA  - Pharmacology
JT  - Pharmacology
JID - 0152016
RN  - 0 (Angiotensin II Type 1 Receptor Blockers)
RN  - 0 (Imidazoles)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tetrazoles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 8W1IQP3U10 (olmesartan)
SB  - IM
MH  - Angiotensin II Type 1 Receptor Blockers/*pharmacology
MH  - Apoptosis/*drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Humans
MH  - Imidazoles/*pharmacology
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Kidney Glomerulus/cytology
MH  - Reactive Oxygen Species/metabolism
MH  - Tetrazoles/*pharmacology
MH  - *Tumor Necrosis Factor-alpha
EDAT- 2012/10/12 06:00
MHDA- 2013/04/24 06:00
CRDT- 2012/10/12 06:00
PHST- 2012/04/04 00:00 [received]
PHST- 2012/09/07 00:00 [accepted]
PHST- 2012/10/12 06:00 [entrez]
PHST- 2012/10/12 06:00 [pubmed]
PHST- 2013/04/24 06:00 [medline]
AID - 000343244 [pii]
AID - 10.1159/000343244 [doi]
PST - ppublish
SO  - Pharmacology. 2012;90(5-6):324-31. doi: 10.1159/000343244. Epub 2012 Oct 9.