Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury

Young Eun Cho, Eun Ju Im, Pyong Gon Moon, Esteban Mezey, Byoung Joon Song, Moon Chang Baek

Research output: Contribution to journalArticle

Abstract

Drug- and alcohol-induced liver injury are a leading cause of liver failure and transplantation. Emerging evidence suggests that extracellular vesicles (EVs) are a source of biomarkers because they contain unique proteins reflecting the identity and tissue-specific origin of the EV proteins. This study aimed to determine whether potentially hepatotoxic agents, such as acetaminophen (APAP) and binge alcohol, can increase the amounts of circulating EVs and evaluate liver-specific EV proteins as potential biomarkers for liver injury. The circulating EVs, isolated from plasma of APAP-exposed, ethanol-fed mice, or alcoholic hepatitis patients versus normal control counterparts, were characterized by proteomics and biochemical methods. Liver specific EV proteins were analyzed by immunoblots and ELISA. The amounts of total and liver-specific proteins in circulating EVs from APAP-treated mice significantly increased in a dose- and time-dependent manner. Proteomic analysis of EVs from APAP-exposed mice revealed that the amounts of liver-specific and/or hepatotoxic proteins were increased compared to those of controls. Additionally, the increased protein amounts in EVs following APAP exposure returned to basal levels when mice were treated with N-acetylcysteine or glutathione. Similar results of increased amounts and liver-specific proteins in circulating EVs were also observed in mice exposed to hepatotoxic doses of thioacetamide or D-galactosamine but not by non-hepatotoxic penicillin or myotoxic bupivacaine. Additionally, binge ethanol exposure significantly elevated liver-specific proteins in circulating EVs from mice and alcoholics with alcoholic hepatitis, compared to control counterparts. These results indicate that circulating EVs in drug- and alcohol-mediated hepatic injury contain liver-specific proteins that could serve as specific biomarkers for hepatotoxicity.

Original languageEnglish (US)
Article numbere0172463
JournalPLoS One
Volume12
Issue number2
DOIs
StatePublished - Feb 1 2017

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Chemical and Drug Induced Liver Injury
Biomarkers
Liver
biomarkers
alcohols
Alcohols
drugs
Acetaminophen
liver
Pharmaceutical Preparations
Proteins
proteins
alcoholic hepatitis
mice
Alcoholic Hepatitis
proteomics
Ethanol
Proteomics
ethanol
Extracellular Vesicles

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury. / Cho, Young Eun; Im, Eun Ju; Moon, Pyong Gon; Mezey, Esteban; Song, Byoung Joon; Baek, Moon Chang.

In: PLoS One, Vol. 12, No. 2, e0172463, 01.02.2017.

Research output: Contribution to journalArticle

Cho, Young Eun ; Im, Eun Ju ; Moon, Pyong Gon ; Mezey, Esteban ; Song, Byoung Joon ; Baek, Moon Chang. / Increased liver-specific proteins in circulating extracellular vesicles as potential biomarkers for drug- and alcohol-induced liver injury. In: PLoS One. 2017 ; Vol. 12, No. 2.
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