The antipyretic effects of baicalin in lipopolysaccharide-evoked fever in rabbits.
Evidence has accumulated to indicate that systemic administration of lipopolysaccharide (LPS), in addition to elevating tumor necrosis factor-alpha (TNF-alpha) as well as fever, induces overproduction of both glutamate and hydroxyl radicals in the rabbit's hypothalamus. Current investigation was attempted to determine whether baicalin exerts its antipyresis by suppressing overproduction of circulating TNF-alpha and hypothalamic glutamate and hydroxyl radicals in rabbits. The microdialysis probes were stereotaxically and chronically implanted into the preoptic anterior hypothalamus of rabbit brain for determination of both glutamate and hydroxyl radicals in situ. It was found that systemic administration of LPS (0.5-10 microg/kg) induced dose-related increased levels of both core temperature and hypothalamic levels of both glutamate and hydroxyl radicals accompanied by increased plasma levels of TNF-alpha. The rise in both the core temperature and hypothalamic glutamate and hydroxyl radicals could also be induced by direct injection of TNF-alpha (1-20 ng) into the lateral ventricle of rabbit brain. Pretreatment with baicalin (2-20 mg/kg, i.v.) one hour before an i.v. dose of LPS significantly reduced the LPS-induced overproduction of circulating TNF-alpha and brain glutamate and hydroxyl radicals. Both the febrile response and overproduction of both glutamate and hydroxyl radicals in the hypothalamus caused by central administration of TNF-alpha could be suppressed by baicalin. These findings suggest that systemic administration of baicalin may exert its antipyresis by inhibiting the N-methyl-D-aspartate receptor-dependent hydroxyl radicals pathways in the hypothalamus and circulating TNF-alpha accumulation during LPS-fever.
Tsai
Cheng-Chia
CC
Institute of Pharmacology, National Yang-Ming University, and Department of Surgery, Mackay Memorial Hospital, Taipei 100, Taiwan.
Lin
Mao-Tsun
MT
Wang
Jhi-Joung
JJ
Liao
Jyh-Fei
JF
Huang
Wu-Tein
WT
D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005334:Fever / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D005419:Flavonoids / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides; D008297:Male; D017551:Microdialysis / Q000379:methods; D011817:Rabbits; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D005419:Flavonoids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D017665:Hydroxyl Radical; C038044:baicalin; D018698:Glutamic Acid