Know what´s inside:

Hepatocytes and Toxicology

Your hepatocyte partner

The GBA Group has been developing its expertise in in vitro ADME-Toxicology with hepatocytes for almost 20 years.

Our services deliver informations with hepatocytes and/or liver subcellular fractions to evaluate inter-species differences and inter-individual variability in safety and drug efficacy, and to explain adverse reactions. The information is helping in optimizing the discovery, development and approval of drugs, food additives, agrochemicals and nutraceuticals.

The GBA Group is actively involved in innovative research in hepatocyte cell biology and in-vitro toxicology. In addition to standard protocol-driven studies we also offer consultation service experience and customized studies. In support of this type of research, we offer liver cellular products from animal and human origin.

Our services

In-vitro screening for CYP induction

Exposure of plated hepatocytes (human, monkey, dog, minipig, rat and mouse)
mRNA expression by RT-qPCR

In-vitro regulatory (FDA/EMA) CYP and UGT induction

Exposure of plated human hepatocytes (from 3 donors), pre-characterized for response to positive control inducers, including for CYP Relative Induction Score

In-vitro metabolic Stability & Metabolite Identification

Metabolic stability influences both oral bioavailability and plasma half-life of a compound, which in turn, affect its efficacy.

The GBA Group evaluates the metabolic stability of xenobiotics and drug candidates in hepatocytes from various species. This analysis compares metabolic stability profiles from human and animal species in order to identify the most relevant animal model for pharmacokinetic and/or toxicity studies.

Exposure of plated hepatocytes from various species, and incubated for several days, up to 7 days, in a sandwich culture configuration allowing long-term culture and incubation

The GBA Group identifies metabolites formed by hepatocytes from various species.

This analysis compares metabolite identification formed by human and animal species in order to identify the most relevant animal model for pharmacokinetic and/or toxicity studies.

Measuring at multiple time-points the concentration of parent compound and metabolites with the help of HPLC/MS (*performed by a member of the GBA Group)

In-vitro and Ex-vivo Acute and Chronic Liver-related Toxicities

Induction, repression or inhibition of major liver metabolic enzymes,
ex-vivo in liver samples from animals of toxicology studies
in-vitro from plated hepatocytes of various species, and exposed for several days, up to 7 days in a sandwich culture configuration allowing long-term culture and incubation
Cell Proliferation
Using RT-qPCR for gene expression and LC-MS detection for enzyme activities (*performed by a member of the GBA Group)

In-vitro and Ex-vivo Drug induced liver injury

The GBA Group offers innovative in vitro read outs of toxicity such as Drug Induced Liver Injury prediction services by measuring separately, or combined, in hepatocytes from various species, the end-points listed below:

Cell viability - General cell viability assessment using single endpoints such as mitochondrial resazurin metabolism, LDH release or ATP content
Oxidative stress - to address hepatic disorders of detoxification pathways
Steatosis - to address hepatic lipid processing disorder, leading to accumulation of triglycerides within the liver cells
Cholestasis - to address bile acid homeostasis disorder in hepatocytes, leading to bile acid accumulation within liver cells, by determining a Drug-Induced-Cholestasis Index (DICI)