Effect of 5-lipoxygenase inhibitor against lipopolysaccharide-induced hypothermia in mice.
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Date
2005-12-20
Authors
Singh, Vijay Pal
Patil, Chandrashekhar S
Kumar, Manish
Kulkarni, Shrinivas K
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Abstract
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.
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Singh VP, Patil CS, Kumar M, Kulkarni SK. Effect of 5-lipoxygenase inhibitor against lipopolysaccharide-induced hypothermia in mice. Indian Journal of Experimental Biology. 2005 Dec; 43(12): 1150-5