Metabolomics-on-a-chip approach to study hepatotoxicity of DDT, permethrin and their mixtures.

Despite the diversity of studies on pesticide toxicities, there is a serious lack of information concerning the toxic effect of pesticides mixtures. Dichlorodiphenyl-trichloroethane (DDT) and permethrin (PMT) are among the most prevalent pesticides in the environment and have been the subject of several toxicological studies. However, there are no data on the toxicity of their mixtures.

Effects of DDT and permethrin on rat hepatocytes cultivated in microfluidic biochips: Metabolomics and gene expression study.

Dichlorodiphenyl-trichloroethane (DDT) and permethrin (PMT) are amongst most prevalent pesticides in the environment. Although their toxicity has been extensively studied, molecular mechanisms and metabolic effects remain unclear, including in liver where their detoxification occurs. Here, we used metabolomics, coupled to RT-qPCR analysis, to examine effects of DDT and PMT on hepatocytes cultivated in biochips.

Long-term human primary hepatocyte cultures in a microfluidic liver biochip show maintenance of mRNA levels and higher drug metabolism compared with Petri cultures.

Human primary hepatocytes were cultivated in a microfluidic bioreactor and in Petri dishes for 13 days. mRNA kinetics in biochips showed an increase in the levels of CYP2B6, CYP2C19, CYP2C8, CYP3A4, CYP1A2, CYP2D6, HNF4a, SULT1A1, UGT1A1 mRNA related genes when compared with post extraction levels. In addition, comparison with Petri dishes showed higher levels of CYP2B6, CYP2C19, CYP2C8, CYP3A4, CYP1A2, CYP2D6 related genes at the end of culture.

Investigation of omeprazole and phenacetin first-pass metabolism in humans using a microscale bioreactor and pharmacokinetic models.

A new in vitro microfluidic platform (integrated insert dynamic microfluidic platform, IIDMP) allowing the co-culture of intestinal Caco-2 TC7 cells and of human primary hepatocytes was used to test the absorption and first-pass metabolism of two drugs: phenacetin and omeprazole. The metabolism of these drugs by CYP1A2, CYP2C19 and CYP3A4 was evaluated by the calculation of bioavailabilities and of intrinsic clearances using a pharmacokinetic (PK) model. To demonstrate the usefulness of the device and of the PK model, predictions were compared with in vitro and in vivo results from the literature.

Investigation of the hepatotoxicity of flutamide: pro-survival/apoptotic and necrotic switch in primary rat hepatocytes characterized by metabolic and transcriptomic profiles in microfluidic liver biochips.

We investigated the effects of the liver damage induced by flutamide in primary rat hepatocytes using liver microfluidic biochips. Flutamide is a non-steroidal anti-androgenic drug. Two flutamide concentrations, 10 μM and 100 μM, were used to expose the hepatocytes for 24h under perfusion.

Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines.

We developed a new biological model to mimic the organ-organ interactions between the intestine and the liver. We coupled polycarbonate cell culture inserts and microfluidic biochips in an integrated fluidic platform allowing dynamic co-cultures (called IIDMP for Integrated Insert in a Dynamic Microfluidic Platform). The intestinal compartment was simulated using Caco-2 TC7 cells and the liver one by HepG2 C3A.

Investigation of expression and activity levels of primary rat hepatocyte detoxication genes under various flow rates and cell densities in microfluidic biochips.

We investigated the behavior of primary rat hepatocytes in biochips using a microfluidic platform (the integrated dynamic cell culture microchip). We studied the effects of cell inoculation densities (0.2-0.

Impact of alginate composition: from bead mechanical properties to encapsulated HepG2/C3A cell activities for in vivo implantation.

Recently, interest has focused on hepatocytes' implantation to provide end stage liver failure patients with a temporary support until spontaneous recovery or a suitable donor becomes available. To avoid cell damage and use of an immunosuppressive treatment, hepatic cells could be implanted after encapsulation in a porous biomaterial of bead or capsule shape. The aim of this study was to compare the production and the physical properties of the beads, together with some hepatic cell functions, resulting from the use of different material combinations for cell microencapsulation: alginate alone or combined with type I collagen with or without poly-L-lysine and alginate coatings.