title: Protective role of indomethacin on lipopolysaccharide-stimulated fever induction and cerebral catecholamine biosynthesis in Wistar rat.
abstract: OBJECTIVE
  The antipyretic and neuroprotective potential of the nonsteroidal anti-inflammatory drug "indomethacin" was tested against lipopolysaccharide-produced hyperthermia and biosynthesis of norepinephrine and dopamine, in six brain regions of male rat.
  
  
  METHODS
  Observations were based on a single intraperitoneal injection of each of lipopolysaccharide (250 µg Kg-1 body wt) and indomethacin (20 mg Kg-1 body wt) followed by sampling and assaying of brain specimens after 2, 8, 12 and 24 hrs. lipopolysaccharide induced a general hyperthermia (8-24 hr) that was completely abolished by pretreatment with indomethacin.
  
  
  RESULTS
  In virtually all brain regions tested, lipopolysaccharide stimulated the biosynthesis of norepinephrine and dopamine. Yet, pretreatment with indomethacin provoked substantial mitigation predominantly after 24 hrs. A time-based manner attended by a regionally nonselective manner characterized lipopolysaccharide-induced monoamine biosynthesis; whereas, indomethacin alleviation seems to proceed in a time-dependent and regionally-selective pathway since the pons proved the fastest and/or most responsive brain region to indomethacin action. A role of prostaglandin synthesis in the development of lipopolysaccharide-induced fever and catecholamine biosynthesis was suggested, given that both responses were abolished by the cyclooxygenase-inhibitor indomethacin.
  
  
  CONCLUSIONS
  Accordingly, our data verified the potent therapy potential of indomethacin in protecting cerebral noradrenergic and dopaminergic systems against lipopolysaccharide-induced acute phase reactions.
authors: Zoology Department, College of Science, King Saud University, Malaz, Riyadh, Kingdom of Saudi Arabia. kadham@ksu.edu.sa
authors: Khadiga G
authors: KG
authors: Adham
authors: Eman M H
authors: EM
authors: Al-Humaidhi
authors: Maha H
authors: MH
authors: Daghestani
authors: Nadia A
authors: NA
authors: Aleisa
authors: Manal H
authors: MH
authors: Farhood
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced / Q000188:drug therapy; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis* / Q000378:metabolism; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D004298:Dopamine; D009638:Norepinephrine; D007213:Indomethacin