The Effect Of Pharmaceuticals To The Early Development Of Xenopus Tropicalis

There is increasing concern about pharmaceuticals and personal care products (PPCPs) since2000. Drugs through human or animal intake, only a few occur metabolism, most of them enter into water environment through the prototype, which potentially harm the survival, growth and development of human. However, human understanding of drugs is very limited, so we need to carry out the research in the toxicity of the pharmaceutiacals. In order to evaluate the ecotoxicity of RXR agonists/inhibitors, amiodarone and clotrimazole, Xenopus tropicalis embryos were exposed to fluorobexarotene, UVI3003, HX531, amodarone and clotrimazole.First, we exposed Xenopus tropicalis embryos to fluorobexarotene. After48h exposure, the most obvious malformation was reduced brain, deformed eyes, hypopigmentaion, displace of cement gland, bent tail and bent axis. In0-12h exposure groups, the effects on embryos were the most serious. We exposed Xenopus tropicalis embryos to UVI3003. UVI3003induced multiple malformations after48h exposure. The most prominent phenotypes included reduced brains, deformed eyes, loss of pigment of eyes, displaced cement gland, enlarged proctodaeum, narrow fins and bent tails. In0-24h exposure groups, the most prominent phenotypes were reduced brains, loss of pigment of eyes, diplaced cement gland and bent tails. In24-48h exposure groups, however, the most prominent phenotypes were loss of pigment of eyes, enlarged proctodaeums and narrow fins. The embryos of exposure grops in all different windows were affected. We exposed Xenopus tropicalis embryos to HX531. HX531induced multiple malformations after48h of exposure. The most obvious malformations were reduced brain, enlarged proctodaeum, edema in heart and narrow fins. In0-24h exposure groups, the most prominent phenotypes were reduced brain, edema in heart, enlarged proctodaeum and narrow fins, but the embryos had no malformation after24-48h exposure. All these results showed that fluorobexarotene, UVI3003and HX531had strong and highly stage-specific teratogenicity in amphibian embryos. Then, we exposed Xenopus tropicalis embryos to combination of UVI30003and TPT. combination of UVI3003and FBA, the results show that when the concentration of TPT was invariant, the degree of malformation was increased with the increasing concentration of UVI3003and when the concentration of UV13003was invariant, the degree of malformation was increased with the increasing concentration of TPT. When the embryos exposed to combined of UVI3003and FBA, the increasing of UVI3003can reduce the malformation in0-24h exposure and increase the malformation in24-48h exposure. All these results showed that RXR agonists and inhibitors can not counteract teratogenicity of each other.Finally, we exposed Xenopus tropicalis embryos to amoidarone and clotrimazole. In acute test, both the percent of survival and the whole body length were slightly decreased in both pharmaceuticals treatment groups compared to the control. In chronic test, the cumulative mortality was22.2%in0.1μg/L clotrimazole treatment group and21.7%in1μg/L amiodarone treatment group. The whole body length and the biomass were significantly decreased, and the developmental stages were also significantly delayed in both pharmaceuticals treatment groups. The results of our study strongly suggest that clotrimazole had adverse side effects on larvae of Xenopus tropicalis at environmentally relevant concentrations.In brief, we can obtain prominent phenotypes using the Xenopus tropicalis embryos for acute test, the results showed that the ecotoxicity of molecular targeted drugs can charactise by the prominent phenotypes. Also we can evaluate the ecotoxicity of non-targeted drugs by using the chronic test with Xenopus tropicalis larvis.With these, we can complete the ecotoxicity evaluation system of pharmceuticals and provide evidences for analysising teratogenic mechanism of pharmaceuticals.