Acute rapamycin( RAP) exposure induce developmental,neurobehavioral and immunal toxicities in embryonic zebrafish

In the present study, we use embryonic zebrafish model to evaluate the RAP's developmental,neurobehavioral and immune toxicity. Wild type AB strain embryos were exposed to various concentrations of RAP solution( 0—5 μmol·L-1) from 8 to120 hours post fertilization( hpf). The RAP concentration that led to malformation in 50% of the embryos( EC50) at 120 hpf was 0. 024 μmol·L-1. The predominant response observed in surviving embryos was yolk sac edema, unabsorbed yolk and uninflated swim bladder. The neurobehavioral toxicity effects included( 1) increased embryonic spontaneous movement frequency at 17—22 hpf and decreased frequency at 23—26 hpf;( 2) 2.5 and 5 μmol·L-1RAP decreased touch response at 27 hpf and 48 hpf;( 3) 0. 01and 0.05 μmol·L-1RAP reduced larval swimming movement speed at 120 hpf. By injection of isothiocyanate dextran with rhodamine B tag,we found that RAP inhibited the absorption of dextran. This may be the reason for the unabsorbed yolk formation under RAP exposure. Using immune transgenic zebrafish MPO strains,RAP decreased the relative fluorescence intensity,decreased the immune cells( neutrophils) and enhanced their sensitivity to inflammation.