title: On the toxicity of kynurenic acid in vivo and in vitro.
abstract: BACKGROUND
  Kynurenic acid (KYNA), a tryptophan metabolite is an antagonist of ionotropic glutamate receptors and alpha-7 nicotinic receptor. Moreover, it is an agonist of G-protein receptor GPR35. Its neuroprotective, anticonvulsant, anti-inflammatory and antioxidant activity was documented. KYNA is present in food and herbal medicines. However, the data on effects induced by a long-lasting treatment with KYNA is lacking. The aim of the study was the assessment of toxicity of a prolonged administration of KYNA in rodents. The cytotoxicity of KYNA in vitro was also examined.
  
  
  METHODS
  Adult mice and rats were used. KYNA was administered in the drinking water in concentrations of 25 or 250mg/L for 3-21 days. The following cells were cultured in an in vitro study: mouse fibroblast (NIH/3T3), green monkey kidney cells and primary chick embryo cells (CECC). Cell viability was determined with methyl thiazol tetrazolium reduction assay, neutral red uptake assay and lactate dehydrogenase leakage assay.
  
  
  RESULTS
  KYNA affected neither body gain nor body composition. Blood counts were also unaffected. The viability of cells in the culture was lowered at high millimolar concentrations of KYNA. An elevated viability of GMK and CECC cells was detected in the presence of KYNA in micromolar concentrations.
  
  
  CONCLUSIONS
  The obtained results showed that a long-term application of KYNA in the drinking water is well-tolerated by rodents. No evidence of a toxic response was recorded. Achieved results indicate that diets containing a high amount of KYNA or enriched with KYNA should not cause any risk to the human health.
authors.affiliation: Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland. Electronic address: turskiwa@op.pl.
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Turski
authors.affiliation: Department of Microbiology and Clinical Immunology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Małaczewska
authors.affiliation: Department of Pharmacology, Medical University, Lublin, Poland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Marciniak
authors.affiliation: Department of Orthopedics and Rehabilitation, Medical University, Lublin, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bednarski
authors.affiliation: Department of Surgery and Surgical Nursing, Medical University, Lublin, Poland.
authors.forename: Michał P
authors.initials: MP
authors.lastname: Turski
authors.affiliation: Department of Orthopedics and Rehabilitation, Medical University, Lublin, Poland.
authors.forename: Mirosław
authors.initials: M
authors.lastname: Jabłoński
authors.affiliation: Department of Microbiology and Clinical Immunology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Olsztyn, Poland.
authors.forename: Andrzej K
authors.initials: AK
authors.lastname: Siwicki
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D005347:Fibroblasts; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D041681:NIH 3T3 Cells; D051381:Rats
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007736:Kynurenic Acid
keywords: In vitro; Kynurenic acid; Mice; Rats; Toxicity