Key result
NecroX-5 exerted anti-inflammatory and anti-fibrotic effects against cardiac hypoxia/reoxygenation injuries by significantly increasing decorin expression and attenuating TGFβ1 and pSmad2 expression.
p-value: p=<0.05
NecroX-5 demonstrates potential anti-inflammatory and anti-fibrotic effects against cardiac hypoxia/reoxygenation injury by modulating the TNFα/Dcn/TGFβ1/Smad2 pathway.
Should not yet change practice in ischemia-reperfusion injury; hypothesis-generating for NecroX-5 in cardiac fibrosis models.
Inflammatory and fibrotic responses are accelerated during the reperfusion period, and excessive fibrosis and inflammation contribute to cardiac malfunction. NecroX compounds have been shown to protect the liver and heart from ischemia-reperfusion injury. The aim of this study was to further define the role and mechanism of action of NecroX-5 in regulating infl ammation and fi brosis responses in a model of hypoxia/reoxygenation (HR). We utilized HR-treated rat hearts and lipopolysaccharide (LPS)-treated H9C2 culture cells in the presence or absence of NecroX-5 (10 µmol/L) treatment as experimental models. Addition of NecroX-5 signifi cantly increased decorin (Dcn) expression levels in HR-treated hearts. In contrast, expression of transforming growth factor beta 1 (TGFβ1) and Smad2 phosphorylation (pSmad2) was strongly attenuated in NecroX-5-treated hearts. In addition, signifi cantly increased production of tumor necrosis factor alpha (TNFα), TGFβ1, and pSmad2, and markedly decreased Dcn expression levels, were observed in LPS-stimulated H9C2 cells. Interestingly, NecroX-5 supplementation effectively attenuated the increased expression levels of TNFα, TGFβ1, and pSmad2, as well as the decreased expression of Dcn. Thus, our data demonstrate potential antiinflammatory and anti-fibrotic effects of NecroX-5 against cardiac HR injuries via modulation of the TNFα/Dcn/TGFβ1/Smad2 pathway.
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Thu et al. (2016) studied Hypoxia/reoxygenation injury. NecroX-5 vs. Untreated HR or LPS-stimulated controls was evaluated on Decorin (Dcn) and TGFβ1 expression levels (p=<0.05). NecroX-5 exerted anti-inflammatory and anti-fibrotic effects against cardiac hypoxia/reoxygenation injuries by significantly increasing decorin expression and attenuating TGFβ1 and pSmad2 expression.
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