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Using Caco-2 Cells to Study Lipid Transport by the Intestine
Published on: August 20, 2015
Transesterification of p-hydroxybenzoate esters (parabens) by human intestinal (Caco-2) cells
M Lakeram1, A J Paine, D J Lockley
1Pharmaceutical Science Research Division, King's College London, London, UK.
Xenobiotica; the Fate of Foreign Compounds in Biological Systems
|September 15, 2006
Summary
A new metabolic pathway, presystemic transesterification, was discovered in human intestinal cells involving parabens and ethanol. This interaction reduces paraben hydrolysis and may cause drug-alcohol interactions.
Area of Science:
- Pharmacology
- Biochemistry
- Toxicology
Background:
- Paraben preservatives are common in oral products.
- Standard paraben metabolism involves hydrolysis to p-hydroxybenzoic acid and excretion.
- A presystemic transesterification pathway in the human intestine was not previously reported.
Purpose of the Study:
- To investigate the potential for paraben transesterification in human intestinal cells.
- To characterize the kinetics of this novel transesterification reaction.
- To explore the implications of this pathway for paraben metabolism and drug-alcohol interactions.
Main Methods:
- Utilized human intestinal Caco-2 cells and cell homogenates.
- Assessed the impact of varying ethanol concentrations on paraben hydrolysis.
- Determined kinetic parameters (Km, Vmax) for transesterification with different alcohols and paraben esters.
- Studied the influence of time, pH, protein, and substrate concentrations.
Main Results:
- Ethanol significantly reduced paraben hydrolysis in Caco-2 cells.
- Optimal transesterification to ethylparaben occurred at 1.0-2.5% ethanol.
- Kinetic data revealed an enzyme preference for short-chain esters.
- Transesterification rates varied significantly with different alcohols and paraben chain lengths.
Conclusions:
- This study reports the first evidence of transesterification in human intestinal cells.
- Presystemic transesterification can alter paraben disposition in the presence of ethanol.
- This mechanism may lead to unrecognized drug-alcohol interactions and artifacts in in vitro studies.
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