Parabens are esters of para-hydroxybenzoic acid and are one of the most commonly used preservatives in the cosmetic, pharmaceutical and food industries. We come into contact with them in different ways. Regardless of the route of exposure, they are rapidly absorbed and metabolized. Metabolism takes place with non-specific esterases, forming para-hydroxybenzoic acid and the associated alcohol.
As part of our research, we wanted to study the mechanism of absorption of parabens through biological barriers. We were particularly interested if active transport in an eliminatory direction is involved, which could explain the lower permeability of parabens. We also tried to determine where in the membrane their metabolism to para-hydroxybenzoic acid occurs. For this purpose, we used Caco-2 cells and PAMPA as biological and non-biological models to study permeability. To determine if active transport of parabens was present on Caco-2 cells, we monitored the absorption of substances in an absorptive and eliminatory direction. The P-glycoprotein and BCRP inhibitor verapamil was also added to the apical side of the membrane. The obtained samples were analysed using an HPLC system.
The results showed that parabens pass through biological barriers passively. Active transport is therefore not a mechanism that lessens their systemic absorption. By studying metabolism, we discovered that para-hydroxybenzoic acid is formed within the membrane as the parabens pass through it and is also more intensely produced on the apical side of the membrane. In the case of parabens, metabolism is therefore the primary mechanism that to some extent decreases their bioavailability, as para-hydroxybenzoic acid itself is very poorly permeable. The lower activity of esterases in the skin compared to the mucosa of the gastrointestinal tract could help explain why paraben exposure is greater when applied dermally.
|
