A new millifluidic-based gastrointestinal platform to evaluate the effect of simulated dietary methylglyoxal intakes

Abstract

The search for new in vitro modular bioreactors to simulate flow-mediated transport and absorption of chemical substances is a very important issue in toxicology and in drug and bioactive delivery research. The possibility of setting up a dynamic microenvironment leads to experimental conditions that may more closely resemble the in vivo model, especially to measure acute or chronic intake of compounds. We propose a novel millifluidic-based gastrointestinal model as an evolution of the common in vitro methods, to evaluate the exposure to exogenous methylglyoxal (MGO), a highly reactive α-oxoaldehyde responsible for the formation of advanced glycation end products involved in a number of chronic diseases. Gastric and intestinal cells were seeded into two different chambers, creating a multi-compartmental system where fluids dynamically interact with human gastric stromal and intestinal cells. MGO was tested at concentrations simulating different MGO food intakes (meal, daily, and hypothetically weekly). Cell viability was measured over time, and simultaneously, extracellular MGO was quantified by a validated RP-HPLC-DAD method to evaluate its absorption/metabolization. This new platform gives the opportunity to connect different compartments, allowing studying kinetic and metabolic profiles of different substances and representing a very promising alternative to animal models, at least in preliminary investigations.