Aspirin May Exert Its Antipyresis by Inhibiting the N-Methyl-D-aspartate Receptor-Dependent Hydroxyl Radical Pathways in the Hypothalamus

Journal of Pharmacological Sciences

Mao-Tsun Lin²  Ching-Ping Chang³  Ting-Yu Kao⁴  Wu-Tein Huang¹ 

[1] Department of Health Care Administration, Diwan College of Management, Taiwan;Department of Medical Research, Chi Mei Medical Center, Taiwan;Department of Biotechnology, Southern Taiwan University of Technology, Taiwan;Institute of Physiology, National Yang-Ming University School of Medicine, Taiwan

关键词: fever;    lipopolysaccharide;    glutamate;    hydroxyl radical;    aspirin;   

DOI  :  10.1254/jphs.FP0061460

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(26)Cited-By(6)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 E2 (PGE2) in the hypothalamus induced by LPS could be suppressed by aspirin pretreatment. The data indicate that systemic administration of aspirin, in addition to suppressing PGE2 production, may exert its antipyresis by inhibiting the NMDA receptor-dependent hydroxyl radical pathways in the hypothalamus during LPS fever.

【 授权许可】

Unknown