Hepatotoxicity by Acetaminophen and Amiodarone in Zebrafish Embryos

Abstract

: Introduction: Liver is an essential organ for the detoxification of chemicals and play pivotal role in various biochemical and physiological processes hence liver toxicity is one of the major causes for the withdrawal of newly discovered molecules. Characteristics viz. high fecundity rate, transparent eggs, less maintenance cost, livelihood in E3 medium without external feeding make Zebrafish (Danio rerio) suitable vertebral model for the hepatotoxicity assay. Methods: On 3 dpf, embryos were exposed to various concentrations of Acetaminophen and Amiodarone in well plates. This procedure was followed up to day 5. Due to mortality observed in Amiodarone treated group G32 (15 μM) treatment was not performed for. On 6 dpf, embryos were kept in lateral position in agar plates and photography was performed. Captured images were analysed through Image J software. Results: Mortalities were observed in Amiodarone treated groups on day 4 (7.1 % at 25 μM), on day 5 (78.5% and 68.2% at 25 μM and 15 μM ) and day 6 (100%, 78.5% and 64.2% at 25 μM, 15 μM and 10 μM). Statistically significant decreased pixel intensity was observed at 1000 μM, 2000 μM and 5000 μM Acetaminophen concentrations and at 5 μM, 7 μM, 10 μM Amiodarone concentrations. Conclusion: Acetaminophen and Amiodarone have hepatotoxic potential in zebrafish embryos. Amiodarone induces embryo lethality at 10 μM. NOAEL for Amiodarone is 3 μM and for Acetaminophen is 500 μM.Key words: Liver necrosis, Pixel intensity.