Novel hepatotoxicity biomarkers of extracellular vesicle (EV)-associated miRNAs induced by CCl4. (2020)

• Record Type: Journal Article
• Authors: Ono, Ryuichi; Yoshioka, Yusuke; Furukawa, Yusuke; Naruse, Mie; Kuwagata, Makiko; Ochiya, Takahiro; Kitajima, Satoshi; Hirabayashi, Yoko
• Is Part Of: Toxicology reports. Volume 7(2020)
• Page Start: 685
• Page End: 692
• Publication Date: 2020
• Subjects: Exosome -- Extracellular vesicle -- EV -- Hepatotoxicity -- miRNA -- Biomarker -- Carbon tetrachloride (CCl4) -- miR-122 -- miR-192 -- miR423 -- miR-29c -- ALT -- AST; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2020.05.002
• Languages: English
• ISSNs: 2214-7500

Abstract

Graphical abstract: Highlights: Establishment of a highly sensitive "next generation-type" toxicity test for chemical substances and drugs. Isolation of novel hepatotoxicity biomarkers of extracellular vesicle (EV)-associated miRNAs induced by CCl4. miR-122 and miR-192 are highly sensitive hepatotoxicity biomarkers equivalent to ALT and AST. Abstract: Recent findings have revealed that extracellular vesicles (EVs) are secreted from cells and circulate in the blood. EVs are classified as exosomes (40−100 nm), microvesicles (50−1, 000 nm) or apoptotic bodies (500−2, 000 nm). EVs contain mRNAs, microRNAs, and DNAs and have the ability to transfer them from cell to cell. Recently, especially in humans, the diagnostic accuracy of tumor cell type-specific EV-associated miRNAs as biomarkers has been found to be more than 90 %. In addition, microRNAs contained in EVs in blood are being identified as specific biomarkers of chemical-induced inflammation and organ damage. Therefore, microRNAs contained in the EVs released into the blood from tissues and organs in response to adverse events such as exposure to chemical substances and drugs are expected to be useful as novel biomarkers for toxicity assessment. In this study, C57BL/6 J male mice orally dosed with carbon tetrachloride (CCl4) were used as a hepatotoxicity animal model. Here, we report that not only the known hepatotoxicity biomarkers miR-122 and miR-192 but also 42 novel EV-associated biomarkers were upregulated in mice dosed with CCl4. Some of these novel biomarkers may be expected to be able to use for better understanding the mechanism of toxicity. These results suggest that our newly developed protocol using EV-associated miRNAs as a biomarker would accelerate the rapid evaluation of toxicity caused by chemical substances and/or drugs.