Extracellular vesicles: Roles and applications in drug-induced liver injury

Abstract

Extracellular vesicles (EV) are defined as nanosized particles, with a lipid bilayer, that are unable to replicate. There has been an exponential increase of research investigating these particles in a wide array of diseases and deleterious states (inflammation, oxidative stress, drug-induced liver injury) in large part due to increasing recognition of the functional capacity of EVs. Cells can package lipids, proteins, miRNAs, DNA, and RNA into EVs and send these discrete packages of molecular information to distant, recipient cells to alter the physiological state of that cell. EVs are innately heterogeneous as a result of the diverse molecular pathways that are used to generate them. However, this innate heterogeneity of EVs is amplified due to the diversity in isolation techniques and lack of standardized nomenclature in the literature making it unclear if one scientist's "exosome" is another scientist's "microvesicle." One goal of this chapter is to provide the contextual understanding of EV origin so one can discern between divergent nomenclature. Further, the chapter will explore the potential protective and harmful roles that EVs play in DILI, and the potential of EVs and their cargo as a biomarker. The use of EVs as a therapeutic as well as a vector for therapeutic delivery will be discussed.

Keywords: Acetaminophen; Biomarker; Drug-induced liver injury; Exosomes; Extracellular vesicles; Haptens; Idiosyncratic drug-induced liver injury; Microvesicle; Polycyclic aromatic hydrocarbons.