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

Bogdan Sorop,Vlad Laurențiu David ,M Florea ,L Bălan ,Alina Hegheş ,Delia Berceanu-Văduva ,Doru Anastasiu

doi:10.37358/rc.20.7.8267

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.

Highlights

The term folates describes the class of water-soluble vitamins, consisting of a pterin structure, a paminobenzoic acid and a residue of one or more molecules of glutamic acid
One of these is related to the amount of unmetabolized folic acid (FA) that reaches from mother to fetus with adverse consequences due to the resulting poor methylation processes
Given that folate cannot be synthesized by the human body, it must be introduced either through food, or through supplements stating that these compounds, introduced into the body are not metabolically active compounds

Summary

Introduction

The term folates describes the class of water-soluble vitamins, consisting of a pterin structure, a paminobenzoic acid and a residue of one or more molecules of glutamic acid. The importance of folate in growth and development has been studied for decades, but there are mechanisms and processes that have not yet been elucidated or fully understood. One of these is related to the amount of unmetabolized folic acid (FA) that reaches from mother to fetus with adverse consequences due to the resulting poor methylation processes. MTHFR (Methylene Tetra Hydro Folate Reductase) mutations are a key factor especially in the pre-conception period and to prevent genetic abnormalities the administration of methylfolate to the detriment of folic acid is indicated [2].

Methods

Results

Conclusion