Advertisement

Variable Antipyretic Effect of SC-58236, a Selective Cyclooxygenase (COX)-2 Inhibitor, in Rats

  • Eyup S. Akarsu
  • Soner Mamuk
  • Sibel Arat
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 525)

Abstract

Fever is the most common body temperature (Tb) change accompanied to inflammation [1]. It has been reported that increased prostaglandin (PG) formation is generally essential for the genesis of fever [2]. The COX enzyme is required for PG synthesis. There are two isoforms of the COX enzyme as COX-1 and COX-2 [3]. Recent studies have suggested that COX- 2 isoenzyme is critical for the mediation of lipopolysaccharide (LPS)- induced fever in rodents [4,5]. But, our data did not support this suggestion [6]. Briefly, selective inhibitors of COX-2 and COX-1, either alone or in combination, did not inhibit the initiation of the fever component of LPS- induced dual Tb response in rats. It may be proposed that the model we used could be the source of this variance since we observed an initial hypothermia and subsequent fever by LPS at 50 γg/kg dose. The mechanisms of fever may have been determined by the pattern of the response implying that the fever as a component of dual response may have different characteristics than the fever, which develops without hypothermia. In this connection, a lower dose of LPS such as 2 γg/kg produces only fever in our experimental conditions [[7]]. Another source of variability might be related with LPS itself. We have reported that LPS causes serotype-specific Tb changes in rats [[7]]. Thus, it may be proposed that diverse signalling pathways might be activated depending on the dose or the serotype of LPS. In order to evaluate this proposal, the effects of COX-1 or COX-2 selective inhibitors (valeryl salicylate [VS] and SC-58236; respectively) on fever induced by low dose of two different serotype of LPSs were investigated in rats.

Keywords

Febrile Response Dual Response Diverse Signalling Pathway Activate Alternative Pathway Fever Peak 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kluger MJ.Fever Role of pyrogens and cryogens. Physiol Rev 1991; 71: 93–161.Google Scholar
  2. 2.
    Coceani F, Akarsu ES. Prostaglandin E2 in the pathogenesis of fever: An Update. Ann NY Acad Sci 1998; 856:76–81.PubMedCrossRefGoogle Scholar
  3. 3.
    Vane JR, Bakhle, YS, Botting RM. Cyclooxygenase-1 and-2. Ann Rev Pharmacol Toxicol 1998; 38:97–120.CrossRefGoogle Scholar
  4. 4.
    Cao C, Matsumura K, Yamagata K, Watanabe Y. Involvement of cyclooxygenase-2 in LPS-induced fever and regulation of its mRNA by LPS in the rat brain. Am J Physiol 1997; 272: R1712–R1725.PubMedGoogle Scholar
  5. 5.
    Li S, Wang Y, Matsumura K, Ballou LR, Morham SG, Blatteis CM. The febrile response to lipopolysaccharide is blocked in COX-2-/-, but not in COX-1-/-mice. Brain Res 1999; 825:86–94.PubMedCrossRefGoogle Scholar
  6. 6.
    Dogan MD, Ataoglu H, Akarsu ES. Effects of selective COX enzyme inhibitors on lipopolysaccharide-induced dual thermoregulatory changes in rat. Brain Res Bull 2002;57:179–185.PubMedCrossRefGoogle Scholar
  7. 7.
    Dogan MD, Ataoglu H, Akarsu ES. Effects of different serotypes of E. Coli lipopolysaccharides on body temperature in rats. Life Sci 2000; 67:2319–2329.PubMedCrossRefGoogle Scholar
  8. 8.
    Dogan MD, Ataoglu H, Akarsu ES. Polysaccharide components of exogenous pyrogens produce fever in rats. In: Gourine VN, ed. Basic and Applied Thermophysiology. Inst Physiol Natl Acad Sci Rep Belarus, 2000; pp: 26–29.Google Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Eyup S. Akarsu
    • 1
  • Soner Mamuk
    • 1
  • Sibel Arat
    • 1
  1. 1.Faculty of Medicine, Department of Pharmacology and Clinical PharmacologyAnkara UniversityAnkaraTurkey

Personalised recommendations