The weakening effect of soluble epoxide hydrolase inhibitor AUDA on febrile response to lipopolysaccharide and turpentine in rat
| Autor: | Agata J. Pacuła, Wieslaw Kozak, Jacek Ścianowski, Małgorzata Pawlikowska, Tomasz Jędrzejewski, Jakub Piotrowski |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Epoxide hydrolase 2 Lipopolysaccharides Male Lipopolysaccharide Fever Physiology Turpentine Inflammatory response Pharmacology Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Aseptic fever Animals Anti-pyretic Enzyme Inhibitors Rats Wistar Biotelemetry chemistry.chemical_classification Inflammation Epoxide Hydrolases General Medicine Metabolism Rats 030104 developmental biology Enzyme Soluble epoxide hydrolase chemistry Immunology cardiovascular system Original Article EETs 030217 neurology & neurosurgery Olive oil |
| Zdroj: | Journal of Physiology and Biochemistry |
| ISSN: | 1877-8755 1138-7548 |
| Popis: | A still growing body of evidence suggests the importance of epoxyeicosatrienoic acids (EETs) in the regulation of inflammatory response; therefore, drugs that stabilize their levels by targeting the soluble epoxide hydrolase (sEH), an enzyme responsible for their metabolism, are currently under investigation. The effect of sEH inhibitors on molecular components of fever mechanism, i.e., on synthesis of pro-inflammatory cytokines or prostaglandins, has been repeatedly proven; however, the hypothesis that sEH inhibitors affect febrile response has never been tested. The aim of this study was to examine if sEH inhibition affects core body temperature (Tb) as well as Tb changes during febrile response to infectious (lipopolysaccharide; LPS) or non-infectious (turpentine; TRP) stimuli. Male Wistar rats were implanted intra-abdominally with miniature biotelemeters to monitor Tb. A potent sEH inhibitor 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) was suspended in olive oil and administrated into animals in the intraperitoneal (i.p.) dose of 15 mg/kg, which, as we showed, has no significant influence on normal Tb. We have found that AUDA injected 3 h after LPS (50 μg/kg i.p.) significantly weakened febrile rise of Tb. Moreover, injection of sEH inhibitor 7 h after turpentine (administrated subcutaneously in a dose of 100 μL/rat) markedly reduced the peak period of aseptic fever. Obtained results provide first experimental evidence that sEH inhibitors possess anti-pyretic properties. Therefore, medicines targeting sEH enzymatic activity should be considered as a complement to the arsenal of topical medications used to treat fever especially in clinical situations when non-steroidal anti-inflammatory drugs are ineffective. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink