Effect of 5-lipoxygenase inhibitor against lipopolysaccharide-induced hypothermia in mice
Singh, V.Pal.; Patil, C.S.; Kumar, M.; Kulkarni, S.K.
Indian Journal of Experimental Biology 43(12): 1150-1155
2005
ISSN/ISBN: 0019-5189 PMID: 16359126 Document Number: 590636
Bacterial endotoxin produces sepsis associated with alterations in body temperature (fever or hypothermia). The intraperitoneal administration of bacterial endotoxin, lipopolysaccharide (LPS; 50 mu g/mouse) led to a decrease in colonic temperature starting 1hr after the injection. The hypothermic effect was accompanied by a significant increase in hypothalamic leukotriene B-4 (LTB4) and prostaglandin E-2 (PGE(2)) 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 PGE(2) levels. Indomethacin had no effect on LTB4 levels but it reduced PGE(2) levels. These results suggest a possible involvement of leukotrienes in LPS-induced hypothermia and the potential protective role of 5-lipoxygenase inhibitors in endotoxemia.