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Angiotensin II Receptor Blocker Improves Tumor Necrosis Factor-α-Induced Cytotoxicity via Antioxidative Effect in Human Glomerular Endothelial Cells.
MedLine Citation:
PMID:  23052181     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background/Aims: Tumor necrosis factor-α (TNF-α) 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-α-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-α-induced human glomerular EC (HGEC) damage to clarify the renoprotective mechanisms of ARBs. Methods: Cultured HGECs were stimulated by TNF-α, and then cell viability and cytotoxicity were measured by MTT assay and lactate dehydrogenase release assay, respectively. TNF-α-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-α via the inhibition of reactive oxygen species in HGECs. Conclusion: Our findings suggested that olmesartan might have protective effects against TNF-α-induced glomerular EC dysfunction.
Authors:
Yuki Izawa-Ishizawa; Keisuke Ishizawa; Takumi Sakurada; Masaki Imanishi; Licht Miyamoto; Shoko Fujii; Hironori Taira; Yoshitaka Kihira; Yasumasa Ikeda; Shuichi Hamano; Shuhei Tomita; Koichiro Tsuchiya; Toshiaki Tamaki
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-09
Journal Detail:
Title:  Pharmacology     Volume:  90     ISSN:  1423-0313     ISO Abbreviation:  Pharmacology     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0152016     Medline TA:  Pharmacology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  324-331     Citation Subset:  -    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Affiliation:
Department of Pharmacology, The University of Tokushima Graduate School, Tokushima, Japan.
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