Endogenous metabolites investigation of cadiotoxicity induced by astemizole on zebrafish using GC-MS metabonomics / 中国药学杂志

ABSTRACT

OBJECTIVE: To analysis metabolic changes of zebrafish treated by astemizole, and to find potential cardiotoxicity related biomarkers. METHODS: Forty-eight hpf zebrafish was treated by astemizole and cardiac toxicity was denoted with heart rate, sinus venous (SV) -bulbus arteriosus (BA) distance and heart phenotype. Meanwhile, zebrafish tissue samples were obtained and subjected to GC-MS analysis to find potential biomarkers of cardiotoxicity. RESULTS: Heart rate of zebrafish treated by astemizole decreased significantly compared with the control groups accompanied with apparent atrioventricular block and cardiac morphological changes. Metabonomics analysis show that the metabolic profiling distinguished astemizole group from the control group and 12 potential biomarkers, glucose, glycine, lactic acid, creatinine, glutamine, N-acetyl-L-lysine, L-proline, citric acid, L-tyrosine, phosphate, cholesterol, palmitic acid, are identified. CONCLUSION: These results showed that metabonomics based on new model organism, zebrafish, can be used to express the astemizole-induced cardiotoxicity. The biomarkers found contribute to the early warning for drug-induced cardiotoxicity.