Abstract
Nitroalkene derivatives of nitro-oleic acid (OA-NO2) are endogenous lipid products with potent anti-inflammatory properties in vitro. The present study was undertaken to evaluate the in vivo anti-inflammatory effect of OA-NO2 in mice given LPS. Two days before LPS administration, C57BL/6J mice were chronically infused with vehicle (LPS vehicle) or OA-NO2 (LPS OA-NO2) at 200 microg x kg(-1) x day(-1) via osmotic minipumps; LPS was administered via a single intraperitoneal (ip) injection (10 mg/kg in saline). A third group received an ip injection of saline without LPS or OA-NO2 and served as controls. At 18 h of LPS administration, LPS vehicle mice displayed multiorgan dysfunction as evidenced by elevated plasma urea and creatinine (kidney), aspartate aminotransferase (AST) and alanine aminotransferase (ALT; liver), and lactate dehydrogenase (LDH) and reduced ejection fraction (heart). In contrast, the severity of multiorgan dysfunction was less in LPS OA-NO2 animals. The levels of circulating TNF-alpha and renal TNF-alpha mRNA expression, together with renal mRNA expression of monocyte chemoattractant protein-1, ICAM-1, and VCAM-1, and with renal mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase 2, and renal cGMP and PGE2 contents, were greater in LPS vehicle vs. control mice, but were attenuated in LPS OA-NO2 animals. Similar patterns of changes in the expression of inflammatory mediators were observed in the liver. Together, pretreatment with OA-NO2 ameliorated the inflammatory response and multiorgan injury in endotoxin-induced endotoxemia in mice.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alanine Transaminase / blood
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Animals
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Anti-Inflammatory Agents / administration & dosage*
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Aspartate Aminotransferases / blood
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Blood Urea Nitrogen
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Body Temperature / drug effects
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Cell Adhesion Molecules / blood
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Chemokines / blood
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Creatinine / blood
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Cyclic GMP / metabolism
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Cyclooxygenase 2 / metabolism
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Cytokines / blood
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Dinoprostone / metabolism
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Disease Models, Animal
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Drug Administration Schedule
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Endotoxemia / chemically induced
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Endotoxemia / drug therapy*
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Endotoxemia / immunology
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Endotoxemia / physiopathology
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Heart Diseases / immunology
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Heart Diseases / metabolism
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Heart Diseases / physiopathology
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Heart Diseases / prevention & control*
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Hematocrit
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Inflammation Mediators / blood
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Inflammation Mediators / metabolism*
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Infusion Pumps, Implantable
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Kidney / drug effects
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Kidney / immunology
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Kidney / metabolism
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Kidney Diseases / immunology
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Kidney Diseases / metabolism
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Kidney Diseases / physiopathology
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Kidney Diseases / prevention & control*
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Lipopolysaccharides
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Liver / drug effects
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Liver / immunology
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Liver / metabolism
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Liver Diseases / immunology
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Liver Diseases / metabolism
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Liver Diseases / physiopathology
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Liver Diseases / prevention & control*
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Male
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Mice
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Mice, Inbred C57BL
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Myocardium / immunology
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Myocardium / metabolism
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Nitric Oxide Synthase Type II / metabolism
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Oleic Acids / administration & dosage*
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Stroke Volume / drug effects
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Time Factors
Substances
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10-nitro-oleic acid
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Anti-Inflammatory Agents
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Cell Adhesion Molecules
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Chemokines
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Cytokines
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Inflammation Mediators
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Lipopolysaccharides
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Oleic Acids
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Creatinine
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Ptgs2 protein, mouse
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Cyclooxygenase 2
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Aspartate Aminotransferases
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Alanine Transaminase
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Cyclic GMP
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Dinoprostone