Taurodeoxycholic Acid Sodium Salt: Chaperoning Activity & In Vivo Toxicity

Taurodeoxycholic acid sodium salt is intended for use as an internal standard for the quantification of taurodeoxycholic acid by GC- or LC-MS. Taurodeoxycholic acid is a taurine-conjugated form of the secondary bile acid deoxycholic acid. Taurodeoxycholic acid stimulates chloride ion secretion through calcium-activated chloride ion channels and cystic fibrosis transmembrane conductance regulator (CFTR) in Calu-3 airway epithelial cell monolayers when applied basolaterally. Serum levels of taurodeoxycholic acid increase approximately 5-fold within two hours during an oral lipid tolerance test in humans. Demonstrates the utility of Taurodeoxycholic acid sodium salt in improving the analysis of bioactive compounds in food products, facilitating better understanding of food composition and potential health benefits.

Taurodeoxycholic acid sodium salt—Bile Acid with Chaperoning Activity

For centuries, traditional Chinese medicine has valued animal bile for its use in pharmacological and clinical applications. Bile acids are natural products and fundamental components of bile. Taurodeoxycholic acid sodium salt (TUDCA) is a taurine conjugate of ursodeoxycholic acid (UDCA). Based on its choleretic activity and capability of protecting hepatocytes, UDCA has been approved by FDA (US Food and Drug Administration) for treatment of primary biliary cholangitis (previously primary biliary cihrrosis). The advantage of bile acids in therapeutic use is that they might be administrated via oral, subcutaneous, and intravenous routes of application. Furthermore, in most cases they present rather low toxicity to the organism and are able to cross the blood-brain barrier. Recently, the activity of Taurodeoxycholic acid sodium salt has been demonstrated to extend beyond hepatobiliary disorders. Progressing development of modern societies results in increased risk of so-called civilization diseases which include i.e., diabetes, obesity, cardiovascular diseases, or cancer. Most of these disorders are in fact molecularly connected with endoplasmic reticulum (ER) stress and disrupted protein folding machinery. Thus, a group of pharmacological agents possessing potentially beneficial effects against ER stress are known as 'chemical chaperones'.[1]

With all that being said, not every piece of information concerning TUDCA/UDCA activity is so optimistic in pointing to these bile acids as a universal cure for a plenitude of diseases. In light of the available knowledge, it may be stated that although a lot is already known about the biological effects of TUDCA/UDCA in a variety of different cell types and disease models, it is still a very attractive compound to investigate as a potential multifunctional pharmacological agent. Although Taurodeoxycholic acid sodium salt has been known to possess a multitude of activities including ER stress-modulatory, oxidative stress-modulatory, anti-apoptotic, anti-inflammatory, and supposedly epigenetic-modulatory activity in experimental conditions, the clinical relevance of these findings remains unknown and the exact molecular pathways activated after TUDCA treatment in humans are still to be identified. Despite a solid amount of data being already available for this bile acid, further extensive examinations are still performed, unraveling novel roles of TUDCA. This constant interest in unveiling Taurodeoxycholic acid sodium salt biology indicates that there are high expectations and hopes connected with therapeutic opportunities of this bile acid for future use as a natural alternative for many cytoprotective, chemopreventive, and anti-inflammatory drugs.

Toxicity of Taurodeoxycholic acid sodium salt in rats

Taurodeoxycholic acid sodium salt (TDCA) inhibits various inflammatory responses suggesting potential clinical application. However, the toxicity of TDCA has not been evaluated in detail in vivo. We investigated the acute toxicity and 4-week repeated-dose toxicity of TDCA following intravenous infusion under Good Laboratory Practice regulations. In the sighting study of acute toxicity, one of two rats (one male and one female) treated with 300 mg/kg TDCA died with hepatotoxicity, suggesting that the approximate 50% lethal dose of TDCA is 300 mg/kg. Edema and discoloration were observed at the injection sites of tails when rats were infused with 150 mg/kg or higher amount of Taurodeoxycholic acid sodium salt once. In 4-week repeated-dose toxicity study, no treatment-related mortality or systemic changes in hematology and serum biochemistry, organ weights, gross pathology, or histopathology were observed. However, the tail injection site showed redness, discharge, hardening, and crust formation along with histopathological changes such as ulceration, edema, fibrosis, and thrombosis when rats were infused with 20 mg/kg TDCA. Taken together, TDCA induced no systemic toxicity or macroscopic lesions at the injection site at a dose of 10 mg/kg/day, which is 33 times higher than the median effective dose observed in a mouse sepsis model. These findings suggest that Taurodeoxycholic acid sodium salt might have a favorable therapeutic index in clinical applications.[2]

References

[1]Kusaczuk M. Tauroursodeoxycholate-Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives. Cells. 2019 Nov 20;8(12):1471. doi: 10.3390/cells8121471. PMID: 31757001; PMCID: PMC6952947.

[2]Choi, Hyung Jun et al. “Evaluation of acute and subacute toxicity of sodium taurodeoxycholate in rats.” Drug and chemical toxicology vol. 44,3 (2021): 268-276. doi:10.1080/01480545.2019.1609493

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