Exogenous folic acid is not able to inhibit the effects of methotrexate on the folate pathway in zebrafish embryos
2015
Jacabacci, Jessica | Guzzardi, Michael | D'Aversa, Teresa G.
Methotrexate (Mtx) is a teratogen that causes severe abnormalities on developing fetuses. Mtx is also used for treatment of rheumatoid arthritis and leukemia. Folic acid (FA), a B vitamin that is present in prenatal vitamins, and Mtx use the same cellular pathway to cause their effects on organisms. It is of great interest to determine whether FA can overcome the effects of Mtx on a developing embryo. Since Mtx is a competitive inhibitor of dihydrofolate reductase, the enzyme used to make FA; it is hypothesized that an increase in FA will overcome the inhibitory effects of Mtx. Zebrafish (Danio rerio) embryos were treated with Mtx and/or FA and then analyzed for developmental irregularities. These data demonstrate that FA cannot rescue the embryos from the teratogenicity of Mtx. Combined treatment enhanced the developmental abnormalities seen, indicating that exogenous FA cannot be used as a mechanism to overcome the teratogenic effects of Mtx.
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