title: Kynurenic acid attenuates multiorgan dysfunction in rats after heatstroke.
abstract: OBJECTIVE
  To assess whether systemic delivery of kynurenic acid improves the outcomes of heatstroke in rats.
  
  
  METHODS
  Anesthetized rats were divided into 2 major groups and given vehicle solution (isotonic saline 0.3 mL/kg rat weight) or kynurenic acid (30-100 mg in 0.3 mL saline/kg) 4 h before the start of thermal experiments. They were exposed to an ambient temperature of 43 °C for 68 min to induce heatstroke. Another group of rats were exposed to room temperature (26 °C) and used as normothermic controls. Their core temperatures, mean arterial pressures, serum levels of systemic inflammatory response molecules, hypothalamic values of apoptotic cells and neuronal damage scores, and spleen, liver, kidney and lung values of apoptotic cells were determined.
  
  
  RESULTS
  The survival time values during heatstroke for vehicle-treated rats were decreased from the control values of 475-485 min to new values of 83-95 min. Treatment with KYNA (30-100 mg/kg, iv) 4 h before the start of heat stress significantly and dose-dependently decreased the survival time to new values of 152-356 min (P<0.05). Vehicle-treated heatstroke rats displayed hypotension, hypothalamic neuronal degeneration and apoptosis, increased serum levels of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and interleukin-10 (IL-10), and spleen, liver, kidney, and lung apoptosis. KYNA preconditioning protected against hypotension but not hyperthermia and attenuated hypothalamic neuronal degeneration and apoptosis during heatstroke. KYNA preconditioning attenuated spleen, kidney, liver, and lung apoptosis and up-regulated serum IL-10 levels but down-regulated serum TNF-α and ICAM-1 levels during heatstroke.
  
  
  CONCLUSIONS
  Our results suggest that systemic delivery of kynurenic acid may attenuate multiorgan dysfunction in rats after heatstroke.
authors.affiliation: Institute of Biomedical Engineering, Chung Yuan Christian University, Chung Li, Taiwan, China.
authors.forename: Yi-chang
authors.initials: YC
authors.lastname: Hsieh
authors.forename: Ruei-feng
authors.initials: RF
authors.lastname: Chen
authors.forename: Yi-shian
authors.initials: YS
authors.lastname: Yeh
authors.forename: Mao-tsun
authors.initials: MT
authors.lastname: Lin
authors.forename: Jui-hsiang
authors.initials: JH
authors.lastname: Hsieh
authors.forename: Sheng-hsien
authors.initials: SH
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005334:Fever / Q000209:etiology / Q000517:prevention & control; D018883:Heat Stroke / Q000150:complications / Q000188:drug therapy*; D007022:Hypotension / Q000209:etiology / Q000517:prevention & control; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007736:Kynurenic Acid