Tetramethylpyrazine decreases hypothalamic glutamate, hydroxyl radicals and prostaglandin-E 2 and has antipyretic effect
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Inflammation Research
ORIGINAL RESEARCH PAPER
Tetramethylpyrazine decreases hypothalamic glutamate, hydroxyl radicals and prostaglandin-E2 and has antipyretic effects Chin-Hong Chang • Wu-Tein Huang • Cheng-Hsing Kao • Sheng-Hsien Chen Cheng-Hsien Lin
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Received: 23 August 2012 / Revised: 4 February 2013 / Accepted: 12 February 2013 / Published online: 23 March 2013 Ó Springer Basel 2013
Abstract Objective We studied the effects of tetramethylpyrazine (TMP) on the fever, increased plasma levels of tumor necrosis factor-a (TNF-a) and increased hypothalamic levels of glutamate, hydroxyl radicals and prostaglandin-E2 (PGE2) induced by lipopolysaccharide (LPS). Materials and methods 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-a were measured.
Results All the body core temperature, plasma levels of TNF-a, and hypothalamic levels of glutamate, hydroxyl radicals, and PGE2 were up-graded by an intravenous dose of LPS (2 lg/kg). Pretreatment with intravenous TMP (10–40 mg/kg) or intracerebroventricular TMP (130 lg in 20 ll per animal) 1 h 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 1 h after LPS injection. Conclusion TMP preconditioning may cause its antipyretic action by reducing plasma levels of TNF-a as well as hypothalamic levels of glutamate, hydroxyl radicals, and PGE2 in rabbits.
Responsible Editor: Michael Parnham. C.-H. Chang C.-H. Kao Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan C.-H. Kao e-mail: [email protected] C.-H. Chang W.-T. Huang Department of Recreation and Health Care Management, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan S.-H. Chen Department of Obstetrics and Gynecology, Chi Mei Medical Center, Tainan, Taiwan S.-H. Chen Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan C.-H. Lin (&) Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan e-mail: [email protected]
Keywords Fever Tetramethylpyrazine Antipyresis Hypothalamus Glutamate Hydroxyl radicals Prostaglandin-E2
Introduction In rabbits, intravenous lipopolysaccharide (LPS) increased the circulating tumor necrosis factor-alpha (TNF-a) [1, 2] and body core temperature. Systemically administered LPS or centrally injected TNF-a increased hypothalamic levels of glutamate, hydroxyl radicals, and prostaglandin-E2 (PGE2) and body core temperature in rabbits [1–3]. These observations prompt us to think that systemic delivery of LPS may induce fever by stimulating the production of glutamate, hydroxyl radicals, and PGE2 in the hypothalamus [4]. Tetramethylpyrazine (TMP) is a biologically active ingredient first extrac
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