Effects of selective cyclooxygenase enzyme inhibitors on lipopolysaccharide-induced dual thermoregulatory changes in rats.
The effects of selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors (valeryl salicylate and SC-58236, respectively) on Escherichia coli O111:B4 lipopolysaccharide (LPS)-induced dual thermoregulatory changes and serum tumor necrosis factor-alpha elevation were investigated in rats. LPS (50 microg/kg, intraperitoneal) produced an initial hypothermia that was then followed by fever. Serum tumor necrosis factor-alpha levels elevated at the initial phase of hypothermia. Valeryl salicylate injections (20, 40, and 80 mg/kg, subcutaneous [s.c.]) completely inhibited hypothermia without any effect on the elevated serum tumor necrosis factor-alpha levels and on the subsequent fever. On the other hand, SC-58236 injections (10, 20, and 40 mg/kg, s.c.) only partially abolished the hypothermia. SC-58236 had no effect on the initiation of fever, however completely inhibited the maintenance of fever. The serum tumor necrosis factor-alpha elevation was not reduced by SC-58236 treatment. The combination of valeryl salicylate and SC-58236 also failed to inhibit the initiation of fever. These findings suggest that cycloxygenase-1 may have a predominant role for the development of LPS-induced hypothermia, but cyclooxygenase-1 does not seem to be involved in the mediation of LPS-induced fever. Meanwhile, cyclooxgenase-2 may be critical for the late phase rather than the initiation of the fever response in rats.
Dogan
M Devrim
MD
Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Ankara University, Sihhiye 06100 Ankara, Turkey.
Ataoglu
Haluk
H
Akarsu
Eyup S
ES
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000633:toxicity; D016207:Cytokines / Q000502:physiology; D005334:Fever / Q000139:chemically induced* / Q000517:prevention & control; D007035:Hypothermia / Q000097:blood / Q000139:chemically induced*; D007527:Isoenzymes / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011453:Prostaglandins / Q000502:physiology; D011720:Pyrazoles; D051381:Rats; D017208:Rats, Wistar; D012459:Salicylates / Q000494:pharmacology* / Q000633:toxicity; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000096926:Benzenesulfonamides
D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins; D011720:Pyrazoles; D012459:Salicylates; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C119130:4-(5-(4-chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)benzenesulfonamide; D000096926:Benzenesulfonamides; C401835:valerylsalicylate; C496513:Ptgs1 protein, rat