A Rapid Quantitative Assessment Method for Liver Damage Effects of Compounds Based on Zebrafish Liver Partition Area Ratio.

Abstract

Total liver area is a traditional indicator in evaluating compound liver damage with zebrafish models. However, in some experiments, compounds changed zebrafish liver morphology but total liver area showed no significant difference, indicating it is inaccurate for evaluating compound effects on zebrafish liver damage. Therefore, in this study, transgenic zebrafish Tg(l-fabp:EGFP) labeled with liver cells using green fluorescent protein was used to evaluate compound effects on liver by the liver partition area ratio. The coefficient of variation of the total liver area and the liver partition area ratio of normal zebrafish at different development stages was calculated to determine the precision and dispersion of the liver partition area ratio. Three known hepatotoxic compounds (water extract of psoralea, alcohol, and α-naphthalene isothiocyanate) were used to treat zebrafish, and liver partition area ratio was calculated and verified by liver tissue pathological sections. The Pearson correlation coefficient was used to analyze the correlation between the liver partition area ratio, total liver area, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Results showed significant difference in liver partition area ratio between hepatotoxic compound treated group and control group, and it could accurately reflect liver morphology changes. There was a strong correlation between liver partition area ratio and ALT and AST level, whereas that between total liver area and ALT and AST level was low. Therefore, the change in zebrafish liver partition area ratio can be an evaluation indicator for rapid assessment of compound effects on zebrafish liver function damage, more sensitive and accurate than total liver area.