Subject(s)
Child , Humans , Male , Corpus Callosum/abnormalities , Hyperhidrosis/complications , Hypothalamic Diseases/complications , Hypothermia/complications , Hypothyroidism/complications , Cyproheptadine/therapeutic use , Hyperhidrosis/drug therapy , Hypothalamic Diseases/drug therapy , Hypothermia/drug therapy , Hypothyroidism/drug therapy , Magnetic Resonance Imaging , Syndrome , Serotonin Antagonists/therapeutic use , Thyrotropin-Releasing Hormone/deficiency , Thyrotropin/deficiency , Thyroxine/therapeutic useABSTRACT
Bacterial endotoxin produces sepsis associated with alterations in body temperature (fever or hypothermia). The intraperitoneal administration of bacterial endotoxin, lipopolysaccharide (LPS; 50 microg/mouse) led to a decrease in colonic temperature starting 1 hr after the injection. The hypothermic effect was accompanied by a significant increase in hypothalamic leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) levels. 5-lipoxygenase inhibitor, zileuton (200 and 400 mg/kg, po) administered 30 min before LPS challenge significantly prevented hypothermia. However, non-selective cyclooxygenase inhibitor, indomethacin (10, 20 mg/kg, po) did not reverse the hypothermic response. Further, pretreatment of mice with zileuton prevented LPS-stimulated increase in hypothalamic LTB4 levels and caused a relatively small increase in PGE2 levels. Indomethacin had no effect on LTB4 levels but it reduced PGE2 levels. These results suggest a possible involvement of leukotrienes in LPS-induced hypothermia and the potential protective role of 5-lipoxygenase inhibitors in endotoxemia.
Subject(s)
Animals , Arachidonate 5-Lipoxygenase/antagonists & inhibitors , Colon/drug effects , Dinoprostone/metabolism , Female , Hydroxyurea/analogs & derivatives , Hypothalamus/drug effects , Hypothermia/drug therapy , Hypothermia, Induced , Indomethacin/pharmacology , Leukotriene B4/metabolism , Leukotrienes/physiology , Lipopolysaccharides/pharmacology , Lipoxygenase Inhibitors/pharmacology , Male , MiceABSTRACT
The effect of dexamethasone on ethanol-induced hypothermia was investigated in 3.5-month old male Wistar rats (N = 10 animals per group). The animals were pretreated with dexamethasone (2.0 mg/kg, ip; volume of injection = 1 ml/kg) 15 min before ethanol administration (2.0, 3.0 and 4.0 g/kg, ip; 20 per cent w/v) and the colon temperature was monitored with a digital thermometer 30, 60 and 90 min after ethanol administration. Ethanol treatment produced dose-dependent hypothermia throughout the experiment (-1.84 ñ 0.10, -2.79 ñ 0.09 and -3.79 ñ 0.l5 degrees Celsius for 2.0, 3.0 and 4.0 g/kg ethanol, respectively, 30 min after ethanol) but only the effects of 2.0 and 3.0 g/kg ethanol were significantly antagonized (-0.57 ñ 0.09 and - 1.25 ñ 0.10, respectively, 30 min after ethanol) by pretreatment with dexamethasone (ANOVA, P<0.05). These results are in agreement with data from the literature on the rapid antagonism by glucocorticoids of other effects of ethanol. The antagonism was obtained after a short period of time, suggesting that the effect of dexamethasone is different from the classical actions of corticosteroids.