Hepatocytes are the major functional cells of the liver and play a vital role in the metabolism and detoxification of xenobiotics. The use of functionally characterized human hepatocytes has become an essential tool in predictive toxicology.
The functional characterization of human hepatocytes involves evaluating changes in hepatocyte differentiation, metabolism, and toxicity in response to toxicological stimuli. Differentiation can be assessed by measuring the expression of hepatocyte-specific markers, such as albumin and CYP450 enzymes. Metabolism can be evaluated by measuring the activity of xenobiotic metabolizing enzymes, such as CYP450, UGT, and SULT, and by assessing the ability of hepatocytes to transport drugs and chemicals across the membrane.
Toxicity can be assessed by evaluating changes in hepatocyte morphology, cell viability, and function. Morphology can be evaluated by measuring changes in cell size, shape, and granularity. Viability can be assessed using assays such as MTT and LDH assays. Function can be evaluated by measuring changes in albumin secretion, urea production, and bile acid transport.
The use of functionally characterized human hepatocytes offers several advantages in predictive toxicology. These cells provide a more relevant model than animal models or cell lines as they more accurately represent human liver function and metabolism. Additionally, their involvement in xenobiotic metabolism provides a unique opportunity to evaluate the potential toxicity and metabolism of various substances in a relevant physiological context.
In conclusion, the functional characterization of human hepatocytes offers a valuable tool for evaluating the potential toxicity and metabolism of various substances in the liver. Their involvement in xenobiotic metabolism and detoxification make them a relevant model for evaluating the safety and efficacy of drugs, chemicals, and other substances.