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.
Subject(s)
Chromonar/analogs & derivatives , Chromonar/therapeutic use , Endotoxemia/drug therapy , NF-kappa B/antagonists & inhibitors , Salmonella typhi , Animals , Aorta, Thoracic/drug effects , Aorta, Thoracic/metabolism , Aorta, Thoracic/physiology , Electrophoretic Mobility Shift Assay , Endotoxemia/metabolism , Endotoxemia/physiopathology , In Vitro Techniques , Male , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/physiology , NF-kappa B/genetics , NF-kappa B/metabolism , Nitrates/blood , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase Type II , Nitrites/blood , Phenylephrine , RNA, Messenger/antagonists & inhibitors , Rats , Rats, Wistar , Reverse Transcriptase Polymerase Chain Reaction , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/geneticsABSTRACT
A thermophilic anaerobic bacterium designated strain RWcit2T (T = type strain) was isolated from the production water of a petroleum reservoir. The cells of this organism are straight to slightly curved rods that are gram negative and nonmotile. Spore formation has not been demonstrated. Growth occurs at temperatures ranging from 28 to 60 degrees C, with optimum growth occurring at 55 degrees C, and at pH values ranging from 5.5 to 8.6, with optimum growth occurring between pH 7 and 7.6. Growth occurs in media containing 0 to 20 g of NaCl per liter, and optimum growth occurs in the presence of 10 g of NaCl per liter. Strain RWcit2T grows on a range of organic acids, including citrate, pyruvate, malate, fumarate, and tartrate; on protein extracts; and on a limited number of carbohydrates. Sulfur, thiosulfate, and cystine are reduced to hydrogen sulfide. Sulfate, sulfite, and nitrate are not reduced. The DNA base composition is 44 mol% G + C. The 16S ribosomal DNA sequence revealed that strain RWcit2T is a member of the domain Bacteria and forms a branch that is approximately equidistant from Dictyoglomus thermophilium and Thermoanaerobacter spp. (level of similarity, 82%). Strain RWcit2T cannot be placed in any previously described taxon based on its phylogenetic and physiological traits and is named Anaerobaculum thermoterrenum gen. nov., sp. nov.
