Aspirin may exert its antipyresis by inhibiting the N-methyl-D-aspartate receptor-dependent hydroxyl radical pathways in the hypothalamus.
Recent findings have suggested that the N-methyl-D-aspartate (NMDA) receptor-dependent hydroxyl radical pathway in the hypothalamus of rabbit brain may mediate the fever induced by lipopolysaccharide (LPS). The aim of this study was to investigate whether aspirin exerts its antipyresis by suppressing 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 intravenous (i.v.) injection of LPS, in addition to inducing fever, caused increased levels of both glutamate and hydroxyl radicals in the hypothalamus. Pretreatment with aspirin (10 - 60 mg/kg, i.v.) one hour before an i.v. dose of LPS significantly reduced the febrile response and attenuated the LPS-induced increased levels of both glutamate and hydroxyl radicals in the hypothalamus. The increased levels of prostaglandin E(2) (PGE(2)) in the hypothalamus induced by LPS could be suppressed by aspirin pretreatment. The data indicate that systemic administration of aspirin, in addition to suppressing PGE(2) production, may exert its antipyresis by inhibiting the NMDA receptor-dependent hydroxyl radical pathways in the hypothalamus during LPS fever.
Kao
Ting-Yu
TY
Institute of Physiology, National Yang-Ming University School of Medicine, Taipei, Taiwan.
Huang
Wu-Tein
WT
Chang
Ching-Ping
CP
Lin
Mao-Tsun
MT
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D005334:Fever / Q000139:chemically induced / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D017551:Microdialysis; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013238:Stereotaxic Techniques
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D016194:Receptors, N-Methyl-D-Aspartate; D017665:Hydroxyl Radical; D018698:Glutamic Acid; D015232:Dinoprostone; D001241:Aspirin