| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912; and 2 Department of Medicine, University of New Mexico, Albuquerque, New Mexico 87131
In previous reports, we (15, 18) and others (29) demonstrated data showing that various inhibitors of cytochrome P-450/epoxygenase augment fever in rats and mice, indicating that the enzyme may be involved in endogenous antipyresis. The aim of this study was to further test the hypothesis that the P-450-dependent epoxygenase pathway of arachidonic acid is part of the homeostatic system to control the height of fever. Sprague-Dawley rats were implanted with biotelemeters to monitor body temperature. Fever was induced by intraperitoneal injection of lipopolysaccharide (LPS; 80 µg/kg). We demonstrate that intraperitoneal administration of P-450 inducers (bezafibrate and dehydroepiandrosterone, 10 and 100 mg/kg) before LPS reduced fever in rats in a dose-dependent manner. In complementary experiments, rats were implanted with brain cannulas in addition to the biotelemeters. Various isomers of epoxyeicosanoids were administered into the lateral ventricle at doses of 0.01 to 10 µg/rat to test their influence on LPS-induced fever in rats. Four of five isomers were antipyretic in a dose-dependent manner. The most potent antipyretic isomers were 11,12-epoxyeicosatrienoic acid (EET) followed by 14,15-EET, 8,9-EET, and 12(R) hydroxyeicosatetraenoic acid. These data support the hypothesis that the cytochrome P-450/epoxygenase pathway of arachidonate metabolism is part of the endogenous antipyretic system.
biotelemetry; body temperature; lipopolysaccharide; brain stereotaxic surgery; cerebral lateral ventricle; fever mechanism; epoxygenase; bezafibrate; dehydroepiandrosterone; epoxyeicosanoids; epoxyeicosatrienoic acids; hydroxyeicosatetraenoic acids
This article has been cited by other articles:
|
|
 |
|
  W. Zhang, T. Otsuka, N. Sugo, A. Ardeshiri, Y. K. Alhadid, J. J. Iliff, A. E. DeBarber, D. R. Koop, and N. J. Alkayed Soluble Epoxide Hydrolase Gene Deletion Is Protective Against Experimental Cerebral Ischemia Stroke, July 1, 2008; 39(7): 2073 - 2078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. P. Koerner, R. Jacks, A. E. DeBarber, D. Koop, P. Mao, D. F. Grant, and N. J. Alkayed Polymorphisms in the Human Soluble Epoxide Hydrolase Gene EPHX2 Linked to Neuronal Survival after Ischemic Injury J. Neurosci., April 25, 2007; 27(17): 4642 - 4649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Imig Epoxide hydrolase and epoxygenase metabolites as therapeutic targets for renal diseases Am J Physiol Renal Physiol, September 1, 2005; 289(3): F496 - F503. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Le Quere, E. Plee-Gautier, P. Potin, S. Madec, and J.-P. Salaun Human CYP4F3s are the main catalysts in the oxidation of fatty acid epoxides J. Lipid Res., August 1, 2004; 45(8): 1446 - 1458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhao, T. Yamamoto, J. W. Newman, I.-H. Kim, T. Watanabe, B. D. Hammock, J. Stewart, J. S. Pollock, D. M. Pollock, and J. D. Imig Soluble Epoxide Hydrolase Inhibition Protects the Kidney from Hypertension-Induced Damage J. Am. Soc. Nephrol., May 1, 2004; 15(5): 1244 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Foster, K. Gott, M. R. Schuyler, W. Kozak, and Y. Tesfaigzi LPS-induced neutrophilic inflammation and Bcl-2 expression in metaplastic mucous cells Am J Physiol Lung Cell Mol Physiol, August 1, 2003; 285(2): L405 - L414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Miyoshi, K. Nagata, T. Imoto, O. Goto, A. Ishida, and T. Watanabe ANG II is involved in the LPS-induced production of proinflammatory cytokines in dehydrated rats Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R1092 - R1097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Roth and P. Persson What suppresses fever in pregnancy near term? Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2002; 283(3): R798 - R799. [Full Text] [PDF]
|
|
|
|
|
|
A. Mouihate, M-S. Clerget-Froidevaux, K. Nakamura, M. Negishi, J. L. Wallace, and Q. J. Pittman Suppression of fever at near term is associated with reduced COX-2 protein expression in rat hypothalamus Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2002; 283(3): R800 - R805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Islam, R. F. Frye, T. J. Richards, I. Sbeitan, S. S. Donnelly, P. Glue, S. S. Agarwala, and J. M. Kirkwood Differential Effect of IFN{alpha}-2b on the Cytochrome P450 Enzyme System: A Potential Basis of IFN Toxicity and Its Modulation by Other Drugs Clin. Cancer Res., August 1, 2002; 8(8): 2480 - 2487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Roman P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function Physiol Rev, January 1, 2002; 82(1): 131 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. T. Morgan Regulation of Cytochrome P450 by Inflammatory Mediators: Why and How? Drug Metab. Dispos., March 1, 2001; 29(3): 207 - 212. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
