Waldemar A Turski1, Joanna Małaczewska2, Sebastian Marciniak3, Jerzy Bednarski4, Michał P Turski5, Mirosław Jabłoński4, Andrzej K Siwicki2. 1. Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland. Electronic address: turskiwa@op.pl. 2. Department of Microbiology and Clinical Immunology, Faculty of Veterinary Medicine, University of Warmia and Mazury, Olsztyn, Poland. 3. Department of Pharmacology, Medical University, Lublin, Poland. 4. Department of Orthopedics and Rehabilitation, Medical University, Lublin, Poland. 5. Department of Surgery and Surgical Nursing, Medical University, Lublin, Poland.
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.
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.
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