Kynurenic acid (KYNA) is an endogenous antagonist of glutamate in the central nervous system. It is most active as an antagonist at receptors sensitive to N‐methyl‐D‐aspartate (NMDA) which regulate neuronal excitability and plasticity, brain development and behaviour[3]. Peripheral administration of kynurenic acid, at a dose that caused plasma levels to increase 430-fold, resulted in only 4-fold increases in striatal ECF(extracellular fluid) concentrations[4]. KYNA has a significant protective effect on liver injury induced by thioacetamide (TAA)[5].
Kynurenic acid/犬尿喹啉酸 细胞实验
Cell Line
Concentration
Treated Time
Description
References
pancreatic acinar cells
250 µM
8 h
Evaluate the protective effects of KYNA and SZR-72 on LO-induced cellular toxicity, results showed KYNA and SZR-72 significantly reduced LO-induced toxicity
Front Immunol. 2021 Oct 21;12:702764.
murine neonatal cardiomyocytes
20 μM
20 min
KynA decreased mitochondrial ROS production and preserved mitochondrial membrane potential in a GPR35-dependent manner
KYNA and KYNA analogs attenuated TNF-α production induced by heat inactivated Staphylococcus aureus and increased TSG-6 mRNA expression
Front Immunol. 2019 Jun 21;10:1406.
Kynurenic acid/犬尿喹啉酸 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Sprague-Dawley rats
Acute necrotizing pancreatitis
Intraperitoneal injection
300 mg/kg
Single dose, lasted for 24 hours
Evaluate the effects of KYNA and SZR-72 on the severity of acute pancreatitis, results showed 300 mg/kg dose significantly alleviated pancreatitis symptoms
Front Immunol. 2021 Oct 21;12:702764.
C57BL/6J mice
LPS-induced sepsis model
Intraperitoneal injection
50 mg/kg
Administered 24 hours and 2 hours before LPS injection
KA significantly reduced serum IL-1β and IL-18 levels in wild-type mice but had no effect in Nlrp3?/? mice
Front Immunol. 2022 Oct 13;13:1019365
Mice
Cardiac ischemia/reperfusion (I/R) injury model
Intraperitoneal injection
5 mg/kg
Single dose 2 hours or 24 hours prior to ischemia
KynA significantly reduced myocardial infarct size and protected cardiac function by activating GPR35
Science. 2022 Aug 5;377(6606):621-629.
Sprague-Dawley rats
Heatstroke model
Intravenous injection
30–100 mg/kg
Single dose, 4 hours before heat exposure
KYNA preconditioning significantly prolonged survival time in heatstroke rats, attenuated hypotension, hypothalamic neuronal degeneration and apoptosis, reduced apoptosis in spleen, kidney, liver, and lung, upregulated serum IL-10 levels, and downregulated TNF-α and ICAM-1 levels.
Acta Pharmacol Sin. 2011 Feb;32(2):167-74
Polish Longwool sheep
Sheep brain third ventricle cannulation model
Intracerebroventricular infusion
20 µg; 100 µg
4 infusions, 30 min each, at 30 min intervals
To investigate the effect of KYNA on BDNF and TrkB expression in specific brain regions of sheep. Results showed that KYNA significantly increased BDNF protein concentration and mRNA expression in the hippocampal CA3 field, amygdala, and prefrontal cortex, with effects varying by dose and brain region.
Cells. 2024 Nov 21;13(23):1928
Sprague-Dawley rats
Intraabdominal sepsis model
Intraperitoneal injection
160 µM/kg
Twice at 16h and 22h after induction
To evaluate the protective effects of KYNA and its synthetic derivatives on sepsis-associated neutrophil activation and brain mitochondrial dysfunction. Results showed that KYNA and its derivatives significantly reduced sepsis-induced increases in BBB permeability and brain injury marker S100B levels, and improved brain mitochondrial function.
United States, California
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UCLA Cousins Center for Psychoneuroimmunology
Recruiting
Los Angeles, California, United States, 90095
Contact: Gracie Pineda 310-825-8425 grpineda@g.ucla.edu
Principal Investigator: Joshua H Cho, MD, PhD 收起 <<
United States, California
... 展开 >>
UCLA Cousins Center for Psychoneuroimmunology
Recruiting
Los Angeles, California, United States, 90095
Contact: Gracie Pineda 310-825-8425 grpineda@g.ucla.edu
Principal Investigator: Joshua H Cho, MD, PhD 收起 <<
Ireland
... 展开 >> Cork University Hospial
Recruiting
Cork, Ireland
Contact: Gerard Clarke, PhD 00353214901415 g.clarke@ucc.ie
Principal Investigator: Gerard Clarke, PhD
Principal Investigator: Timothy G Dinan, Professor
Principal Investigator: John F Cryan, PhD
University College Cork
Recruiting
Cork, Ireland
Contact: Gerard Clarke, PhD 00353214901415 g.clarke@ucc.ie
Principal Investigator: Gerard Clarke, PhD
Principal Investigator: Timothy G Dinan, Professor
Principal Investigator: John F Cryan, PhD 收起 <<
United States, Maryland
... 展开 >>
Maryland Psychiatric Research Center
Recruiting
Catonsville, Maryland, United States, 21228
Principal Investigator: Robert W. Buchanan, M.D. 收起 <<
United States, Texas
... 展开 >>
Michael E. DeBakey VA Medical Center
Recruiting
Houston, Texas, United States, 77030
Contact: Marijn Lijffijt, PhD 713-798-5642 marijn.lijffijt@bcm.edu
Sub-Investigator: Sanjay J. Mathew, MD
Sub-Investigator: Alan C. Swann, MD 收起 <<
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