Abstract
In this study we investigated, for the first time in vivo, the effect of cloricromene, a cumarine derivative, on NF-kappaB activation in endotoxin-treated rats. Endotoxemia was induced in male rats by the intravenous injection of Salmonella typhosa lipopolysaccharide (LPS; 2 mg/kg/i.v.). In vivo treatment with cloricromene (2 mg/kg/i.v.) 30 min before lipopolysaccharide administration reversed the LPS-induced loss in tone of the aortic rings, improved their reactivity to phenylephrine, decreased both nitric oxide (NO) and TNF-alpha serum levels by inhibiting LPS-induced inducible NO synthase and TNF-alpha mRNA expression, and interestingly inhibited LPS-induced NF-kappaB activation. Our data suggest that cloricromene protects rats from LPS by blocking LPS-induced NF-kappaB activation, leading to inhibition of NO and TNF-alpha overproduction and thereby reversing the LPS-induced vascular hyporeactivity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aorta, Thoracic / drug effects
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Aorta, Thoracic / metabolism
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Aorta, Thoracic / physiology
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Chromonar / analogs & derivatives*
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Chromonar / therapeutic use*
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Electrophoretic Mobility Shift Assay
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Endotoxemia / drug therapy*
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Endotoxemia / metabolism
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Endotoxemia / physiopathology
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In Vitro Techniques
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Male
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Muscle Contraction / drug effects
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / physiology
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NF-kappa B / antagonists & inhibitors*
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Nitrates / blood
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / genetics
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Nitric Oxide Synthase Type II
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Nitrites / blood
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Phenylephrine
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RNA, Messenger / antagonists & inhibitors
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Rats
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Rats, Wistar
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Reverse Transcriptase Polymerase Chain Reaction
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Salmonella typhi*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / genetics
Substances
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NF-kappa B
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Nitrates
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Nitrites
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Phenylephrine
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cloricromen
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, rat
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Chromonar