Overview of extracellular microvesicles in drug metabolism

Abstract

Importance of the field: Liver is the major body reservoir for enzymes involved in the metabolism of endogenous and xenobiotic compounds. Recently, it has been shown that hepatocytes release exosome-like vesicles to the extracellular medium, and the proteomic characterization of these hepatocyte-secreted exosomes has revealed the presence of several of these enzymes on them.

Areas covered in this review: A systematic bibliographic search focused on two related aspects: i) xenobiotic-metabolizing enzymes that have been detected in microvesicles (MVs); and ii) MVs that are in the blood stream or secreted by cell types with clear interactions with this fluid.

What the reader will gain: A discussion of these hepatocyte-secreted vesicles along with other MVs as enzymatic carriers in the context of extrahepatic drug-metabolizing systems.

Take home message: The contribution of many tissues including the liver to the MV plasma population is supported by several reports. On the other hand, many enzymes involved in the metabolism of drugs have been detected in MVs. Together, these observations support a role of hepatic-MVs in spreading the liver metabolizing activities through the body contributing in this manner to extrahepatic drug metabolism systems what could be relevant for body homeostasis and pharmaceutical interests.

Keywords::

• cytochromes
• drug metabolism
• exosomes
• extrahepatic
• microvesicles

Acknowledgements

J Conde-Vancells and E Gonzalez equally contributed to this work.

Notes

This box summarizes key points contained in the article.