Evaluation of acute and subacute toxicity of sodium taurodeoxycholate in rats. (4th May 2021)

• Record Type: Journal Article
• Authors: Choi, Hyung Jun; Yun, Jun-Won; Kim, Youn-Hee; Kwon, Euna; Hyon, Min-Kyong; Kim, Ji Young; Che, Jeong-Hwan; Ho Kim, Woo; Seong, Seung-Yong; Kang, Byeong-Cheol
• Is Part Of: Drug and chemical toxicology. Volume 44:Number 3(2021)
• Page Start: 268
• Page End: 276
• Publication Date: 2021-05-04
• Subjects: Taurodeoxycholate -- acute toxicity -- subacute toxicity -- bile acid -- sepsis; Toxicology -- Periodicals; Drugs -- Toxicology -- Periodicals; Toxicology, Experimental -- Periodicals; 615.9005
• DOI: 10.1080/01480545.2019.1609493
• Languages: English
• ISSNs: 0148-0545

Abstract

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.