Effect of 5-lipoxygenase inhibitor against lipopolysaccharide-induced hypothermia in mice.
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.
Singh
Vijay Pal
VP
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160 014, India.
Patil
Chandrashekhar S
CS
Kumar
Manish
M
Kulkarni
Shrinivas K
SK
D000818:Animals; D003106:Colon / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006918:Hydroxyurea / Q000031:analogs & derivatives / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects; D007035:Hypothermia / Q000188:drug therapy* / Q000401:mortality; D007036:Hypothermia, Induced; D007213:Indomethacin / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D015289:Leukotrienes / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice
D015289:Leukotrienes; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D007975:Leukotriene B4; D015232:Dinoprostone; C063449:zileuton; D006918:Hydroxyurea; D007213:Indomethacin