Folates and Anti-folates � Chemical Perspectives, in vitro and in ovo Assessments

Abstract

Folates participate in DNA replication reactions, act as a substrate in enzymatic reactions related to amino acid synthesis and vitamin metabolism while antifolates participate in reactions that inhibit the formation of tetrahydrofolate with consequences on protein and nucleic acid synthesis and implicitly on growth and development both types of cells, healthy and diseased. In the present study, the viability of healthy cells, keratinocytes and human fibroblasts was evaluated in the presence of three folates (folic, dihydrofolic and tetrahydrofolic acids), one antifolate (methotrexate) and combinations between them by Alamar blue assay. The antiangiogenic potential was also evaluated by in ovo technique, CAM assay. Cell viability was influenced in a cell-dependent and dose-dependent manner, fibroblasts being more sensitive to the action of the test compounds, especially the combination of metrotrexate and dihydrofolate. Data related to CAM assay showed that methotrexate revealed a slightly higher vessel density, but without inducing toxicity on vascular architecture and functionality. The data obtained highlight the greater sensitivity of the viability of fibroblasts in the presence of metrotrexate and its combinations with folates used in the study.