Tetramethylpyrazine decreases hypothalamic glutamate, hydroxyl radicals and prostaglandin-E2 and has antipyretic effects

Abstract

We studied the effects of tetramethylpyrazine (TMP) on the fever, increased plasma levels of tumor necrosis factor-α (TNF-α) and increased hypothalamic levels of glutamate, hydroxyl radicals and prostaglandin-E2 (PGE2) induced by lipopolysaccharide (LPS). The microdialysis probes were stereotaxically and chronically implanted into the hypothalamus of rabbit brain for determining extracellular levels of glutamate, hydroxyl radials, and PGE2. In addition, both the body core temperature and plasma levels of TNF-α were measured. All the body core temperature, plasma levels of TNF-α, and hypothalamic levels of glutamate, hydroxyl radicals, and PGE2 were up-graded by an intravenous dose of LPS (2μg/kg). Pretreatment with intravenous TMP (10-40mg/kg) or intracerebroventricular TMP (130μg in 20μl per animal) 1h before LPS administration significantly attenuated the LPS-induced fever as well as the increased hypothalamic levels of glutamate, hydroxyl radicals, and PGE2. LPS-induced fever could also be attenuated by intravenous or intracerebroventricular TMP 1h after LPS injection. TMP preconditioning may cause its antipyretic action by reducing plasma levels of TNF-α as well as hypothalamic levels of glutamate, hydroxyl radicals, and PGE2 in rabbits.