2. Academic Validation
  3. Evaluation of acute and subacute toxicity of sodium taurodeoxycholate in rats

Evaluation of acute and subacute toxicity of sodium taurodeoxycholate in rats

  • Drug Chem Toxicol. 2021 May;44(3):268-276. doi: 10.1080/01480545.2019.1609493.
Hyung Jun Choi 1 2,  Jun-Won Yun 3,  Youn-Hee Kim 4,  Euna Kwon 2,  Min-Kyong Hyon 1 2,  Ji Young Kim 1 2,  Jeong-Hwan Che 5,  Woo Ho Kim 6,  Seung-Yong Seong 4,  Byeong-Cheol Kang 1 2 5 7
Affiliations

Affiliations

  • 1 Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 2 Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
  • 3 Department of Biotechnology, The Catholic University of Korea, Bucheon, Republic of Korea.
  • 4 Wide River Institute of Immunology, Department of Microbiology and Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 5 Biomedical Center for Animal Resource and Development, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 6 Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 7 Designed Animal and Transplantation Research Institute, Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun, Gangwon-do, Republic of Korea.
PMID: 31215257 DOI: 10.1080/01480545.2019.1609493
Abstract

Taurodeoxycholate (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 TDCA 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 TDCA might have a favorable therapeutic index in clinical applications.

Keywords

Taurodeoxycholate; acute toxicity; bile acid; sepsis; subacute toxicity.

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