TY - JOUR
T1 - Curcumin inhibits the increase of glutamate, hydroxyl radicals and PGE2 in the hypothalamus and reduces fever during LPS-induced systemic inflammation in rabbits
AU - Huang, Wu Tein
AU - Niu, Ko Chi
AU - Chang, Chen Kuei
AU - Lin, Mao Tsun
AU - Chang, Ching Ping
N1 - Funding Information:
This work was supported in part by the National Science Council (Taipei, Taiwan, Republic of China) NSC 96-2314-B-384-002 and NSC 96-2314-B-384-003-MY3.
PY - 2008/9/28
Y1 - 2008/9/28
N2 - Evidence has accumulated to suggest that systemic administration of lipopolysaccharide (LPS), in addition to elevating tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) as well as fever, induces overproduction of glutamate, hydroxyl radicals and prostaglandin E2 (PGE2) in the rabbit's hypothalamus. Current study was attempted to assess whether Curcumin exerts its antipyresis by reducing circulating pro-inflammatory cytokines and hypothalamic glutamate, hydroxyl radicals and PGE2 in rabbits. The microdialysis probes were stereotaxically and chronically implanted into the preoptic anterior hypothalamus of rabbit brain for determination of glutamate, hydroxyl radicals, and PGE2 in situ. It was found that systemic administration of LPS (2 μg/kg) induced increased levels of both core temperature and hypothalamic levels of both glutamate and hydroxyl radicals accompanied by increased plasma levels of TNF-α, IL-1β, and IL-6. The rise in both the core temperature and hypothalamic glutamate and hydroxyl radicals could also be induced by direct injection of TNF-α, IL-1β, or IL-6 into the lateral ventricle of rabbit brain. Pretreatment with Curcumin (5-40 mg/kg, i.p.) 1 h before an i.v. dose of LPS significantly reduced the LPS-induced overproduction of circulating TNF-α, IL-1β, and IL-6, and brain glutamate, PGE2, and hydroxyl radicals. Both the febrile response and overproduction of both glutamate and hydroxyl radicals in the hypothalamus caused by central administration of TNF-α, IL-1β, or IL-6 could be suppressed by Curcumin. These results indicate that systemic injection of Curcumin may exert its antipyresis by inhibiting the glutamate-hydroxyl radicals-PGE2 pathways in the hypothalamus and circulating TNF-α, IL-1β, and IL-6 accumulation during LPS fever.
AB - Evidence has accumulated to suggest that systemic administration of lipopolysaccharide (LPS), in addition to elevating tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) as well as fever, induces overproduction of glutamate, hydroxyl radicals and prostaglandin E2 (PGE2) in the rabbit's hypothalamus. Current study was attempted to assess whether Curcumin exerts its antipyresis by reducing circulating pro-inflammatory cytokines and hypothalamic glutamate, hydroxyl radicals and PGE2 in rabbits. The microdialysis probes were stereotaxically and chronically implanted into the preoptic anterior hypothalamus of rabbit brain for determination of glutamate, hydroxyl radicals, and PGE2 in situ. It was found that systemic administration of LPS (2 μg/kg) induced increased levels of both core temperature and hypothalamic levels of both glutamate and hydroxyl radicals accompanied by increased plasma levels of TNF-α, IL-1β, and IL-6. The rise in both the core temperature and hypothalamic glutamate and hydroxyl radicals could also be induced by direct injection of TNF-α, IL-1β, or IL-6 into the lateral ventricle of rabbit brain. Pretreatment with Curcumin (5-40 mg/kg, i.p.) 1 h before an i.v. dose of LPS significantly reduced the LPS-induced overproduction of circulating TNF-α, IL-1β, and IL-6, and brain glutamate, PGE2, and hydroxyl radicals. Both the febrile response and overproduction of both glutamate and hydroxyl radicals in the hypothalamus caused by central administration of TNF-α, IL-1β, or IL-6 could be suppressed by Curcumin. These results indicate that systemic injection of Curcumin may exert its antipyresis by inhibiting the glutamate-hydroxyl radicals-PGE2 pathways in the hypothalamus and circulating TNF-α, IL-1β, and IL-6 accumulation during LPS fever.
KW - Antipyresis
KW - Curcumin
KW - Fever
KW - Glutamate
KW - Hydroxyl radical
KW - Lipopolysaccharide
KW - Prostaglandin E
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U2 - 10.1016/j.ejphar.2008.07.017
DO - 10.1016/j.ejphar.2008.07.017
M3 - Article
C2 - 18664365
AN - SCOPUS:49949097651
SN - 0014-2999
VL - 593
SP - 105
EP - 111
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -