Study on the acute toxicity of sodium taurocholate via zebrafish mortality, behavioral response, and NMR-metabolomics analysis

Abstract

Sodium taurocholate (NaT) is a hydrophobic bile salt that exhibits varying toxicity and antimicrobial activity. The accumulation of BSs during their entero-hepatic cycle causes cytotoxicity in the liver and intestine and could also alter the intestinal microbiome leading to various diseases. In this research, the acute toxicity of sodium taurocholate in different concentrations (3000 mg/L, 1500 mg/L, 750 mg/L, 375 mg/L, and 0 mg/L) was investigated on four months old zebrafish by immersion in water for 96 h. The results were determined based on the fish mortality, behavioral response, and NMR metabolomics analysis which revealed LC50 of 1760.32 mg/L and 1050.42 mg/L after 72 and 96 h treatment, respectively. However, the non-lethal NaT concentrations of 750 mg/L and 375 mg/L at 96 h exposure significantly (p ≤ 0.05) decreased the total distance traveled and the activity duration, also caused surface respiration on the zebrafish. Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) revealed that the metabolome of the fish treated with 750 mg/L was discriminated from that of the control by PC1. Major significantly downregulated metabolites by NaT-induction include valine, isoleucine, 2-hydroxyvalerate, glycine, glycerol, choline, glucose, pyruvate, anserine, threonine, carnitine and homoserine. On the contrary, taurine, creatine, lactate, acetate and 3-hydroxybutyrate were upregulated suggesting cellular consumption of lipids, glucose and amino acids for adenosine triphosphate (ATP) generation during immune and inflammatory response. whereby these metabolites were released in the process. In conclusion, the research revealed the toxic effect of NaT and its potential to trigger changes in zebrafish metabolism.