Protective effects of genistein and estradiol on PAHs-induced developmental toxicity in zebrafish embryos

The toxicity of exposure to polycyclic aromatic hydrocarbons (PAHs) or phytoestrogen is relatively well characterized. However, the toxicity of combined exposure to PAHs and phytoestrogen is not well investigated. In the present study, benzo(a)pyrene (B(a)P) and benzo(k)fluorathene (B(k)F), genistein, along with 17β-estradiol (E2), were investigated for their single and combined developmental toxicity using zebrafish embryos as model system. We demonstrated that two representative PAHs, both B(a)P (≥1 μM) and B(k)F (≥10 μM), can cause significant malformation and mortality in developing zebrafish embryos. The toxicity effect of B(a)P was in general higher than that of B(k)F. Developmental exposure to high level of genistein (>20 μM) or E2 (>10 μM), also caused significant malformation and mortality in zebrafish larvae at 120 hours post fertilization (hpf). However, different toxic effects were observed for the combined exposure to PAHs and phytoestrogen in zebrafish. Lower doses of genistein (1 and 10 μM) and E2 (0.1 and 1 μM), when used in combination with high concentration of B(a)P (1 μM) or B(k)F (20 μM), can significantly suppress the toxicity effect of B(a)P and B(k)F in developing zebrafish embryos. The beneficial effect of genistein may be due to the inhibition of cytochrome P450 enzymes via directly interacting with aryl-hydrocarbon receptor (AhR) pathway, or disturbing the AhR pathway through interacting with estrogen receptor pathway.