Key result
RNH-6270 suppresses TNF-α-induced endothelial cell death and ICAM-1 expression by inhibiting reactive oxygen species.
Why the study?
The effects of olmesartan on TNF-α-induced glomerular endothelial cell damage have not been investigated.
Does RNH-6270 prevent TNF-α-induced cytotoxicity and oxidative stress in human glomerular endothelial cells?
Does RNH-6270 prevent TNF-α-induced cytotoxicity and oxidative stress in human glomerular endothelial cells?
RNH-6270, an active metabolite of olmesartan, protects human glomerular endothelial cells against TNF-α-induced dysfunction by inhibiting reactive oxygen species.
Answers are grounded in this paper and cite their sources.
Suggests olmesartan protects ECs from TNF-α independently of angiotensin II; leaves open clinical renal benefit.
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.
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Izawa‐Ishizawa et al. (2012) studied TNF-α-induced glomerular endothelial cell damage. RNH-6270 (active metabolite of olmesartan) vs. TNF-α stimulation alone was evaluated on Cell viability, cytotoxicity, oxidative stress, and ICAM-1 expression. RNH-6270 suppressed cell death and the increase in ICAM-1 expression induced by TNF-α via the inhibition of reactive oxygen species in human glomerular endothelial cells.
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