Steatosis is characterized by abnormal retention of lipids within an organ and is most common within the liver due to the liver’s role in lipid metabolism. Excess lipid accumulation within the liver can be brought on by a variety of hepatocellular insults, including but not limited to, those induced by drugs or as the outcome of the progression of a pathophysiological disease. Hepatotoxicity is a leading exclusion factor during the drug development process. Assays that allow for the in vitro evaluation of key components of hepatotoxicity, such as steatosis, are key to the future of drug development.
Early screening for hepatotoxicity is important for narrowing down potential candidates during drug development. Both 2D and 3D in vitro liver models can offer valuable information regarding lipid accumulation with each having its own pros and cons. 2D assays are typically more cost effective and easier to scale-up for large screening campaigns while 3D assays are more similar to in vivo conditions and can be a better predictor of toxicological profiles.
Visikol offers a wide array of screening platforms for the evaluation of lipid retention after compound treatment. Our 2D and 3D liver cell models range from hepatocyte-only models (HepaRG or primary hepatocytes) to models that incorporate both hepatocytes and non-parenchymal cells, based on a client’s needs. A typical screen evaluates the client compound under a fatty acid free bovine serum albumin (BSA) control treatment and a free fatty acid (palmitic acid and oleic acid) treatment. The cells are then fixed and the lipid accumulation evaluated using Thermo Fisher’s LipidTOX neutral lipid stain. Variations on these assays can also be used to evaluate other aspects of hepatotoxicity, such as: apoptosis, mitochondrial health, and reactive oxygen species (ROS) production.
If you are interested in determining the impact of your target compounds on steatosis of the liver or if you have an interest in any other assay Visikol offers, please feel free to contact us.