Unstability of cinnabarinic acid, an endogenous metabolite of tryptophan, under situations mimicking physiological conditions

Gómez-Piñeiro, Rogelio J; Dali, Madou; Mansuy, Daniel; Boucher, Jean‐Luc

doi:10.1016/j.biochi.2022.04.009

Cited by 2 publications

(3 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One may not exclude, however, that it is not a lack of scientific community interest in CA but rather the technical difficulties for its measurement that have brought about the situation wherein it is less investigated than the other kynurenine pathway metabolites. The latest study of Gómez-Piñeiro et al [ 54 ] also shows that CA is unstable under physiological conditions, and that, in the presence of reductants, it readily metabolizes to other products. Thus, this may also be another reason that its levels are below the detection limit.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…Very recently, Gómez-Piñeiro et al [54] provided new data about the metabolism and stability of CA under physiological conditions, with CA's stability being studied under varied conditions (solvent, aerobic/anaerobic conditions, pH, temperature). In the initial experiment, CA was dissolved in DMSO, methanol, and acetonitrile to methanol 1:1 at 37 • C. Regardless of the solvent, under such conditions, the CA was stable up to 8 h.…”

Section: Cinnabarinic Acid Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

A Review on the Role and Function of Cinnabarinic Acid, a “Forgotten” Metabolite of the Kynurenine Pathway

Gawel

2024

Cells

View full text Add to dashboard Cite

In the human body, the majority of tryptophan is metabolized through the kynurenine pathway. This consists of several metabolites collectively called the kynurenines and includes, among others, kynurenic acid, L-kynurenine, or quinolinic acid. The wealth of metabolites, as well as the associated molecular targets and biological pathways, bring about a situation wherein even a slight imbalance in the kynurenine levels, both in the periphery and central nervous system, have broad consequences regarding general health. Cinnabarinic acid (CA) is the least known trace kynurenine, and its physiological and pathological roles are not widely understood. Some studies, however, indicate that it might be neuroprotective. Information on its hepatoprotective properties have also emerged, although these are pioneering studies and need to be replicated. Therefore, in this review, I aim to present and critically discuss the current knowledge on CA and its role in physiological and pathological settings to guide future studies.

show abstract

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Section: Cinnabarinic Acid Chemistrymentioning

confidence: 99%

A Review on the Role and Function of Cinnabarinic Acid, a “Forgotten” Metabolite of the Kynurenine Pathway

Gawel

2024

Cells

View full text Add to dashboard Cite

show abstract

“…These observations indicate that from a clinically relevant therapeutic perspective, a pharmacotherapeutic formulation or dietary supplementation of CA will be essential for activating AhR-Stc2 mediated hepatoprotective signaling pathways. A recent study indicated half-life of CA to be 4 hr in an isolated rat liver microsomes (Gómez-Piñeiro et al, 2022), therefore future studies will need to be performed to comprehensively examine mechanism of CA production within endogenous tryptophan metabolism pathway, and determine in vivo stability of CA.…”

Section: Ca Regulates Lipid Metabolism In Vivomentioning

confidence: 99%

Cinnabarinic Acid Provides Hepatoprotection Against Nonalcoholic Fatty Liver Disease

Patil

Rus

Downing

et al. 2022

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) is a chronic condition in which excess lipids accumulate in the liver and can lead to a range of progressive liver disorders including non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. While lifestyle and diet modifications have proven to be effective as NAFLD treatments, they are not sustainable in long-term and currently no pharmacological therapies are approved to treat NAFLD. Our previous studies demonstrated that cinnabarinic acid (CA), a novel endogenous Aryl hydrocarbon Receptor (AhR) agonist activates AhR target gene, Stanniocalcin 2 and confers cytoprotection against a plethora of ER/oxidative stressors. In this study, the hepatoprotective and anti-steatotic properties of CA were examined against free fatty acid-induced in vitro and high-fat diet-fed in vivo NAFLD models. The results demonstrated that CA treatment significantly lowered weight gain and attenuated hepatic lipotoxicity both before and after established fatty liver, thereby protecting against steatosis, inflammation and liver injury. CA mitigated intracellular free fatty acid uptake concomitant with the downregulation of CD36/fatty acid translocase. Genes involved in fatty acid and triglyceride synthesis were also downregulated in response to CA treatment. Additionally, suppressing AhR and Stc2 expression using RNA interference in vitro verified that the hepatoprotective effects of CA were absolutely dependent on both AhR and its target, Stc2. Collectively, our results demonstrate that endogenous AhR agonist, CA confers hepatoprotection against NAFLD by regulating hepatic fatty acid uptake and lipogenesis.

show abstract

Unstability of cinnabarinic acid, an endogenous metabolite of tryptophan, under situations mimicking physiological conditions

Cited by 2 publications

References 44 publications

A Review on the Role and Function of Cinnabarinic Acid, a “Forgotten” Metabolite of the Kynurenine Pathway

A Review on the Role and Function of Cinnabarinic Acid, a “Forgotten” Metabolite of the Kynurenine Pathway

Cinnabarinic Acid Provides Hepatoprotection Against Nonalcoholic Fatty Liver Disease

Contact Info

Product

Resources

About