Evaluation of miR-122 to Predict High Dose Acetaminophen-Induced Liver Injury in Mice: The Combination Uses of 5-Fluorouracil

Administration of high doses of acetaminophen (APAP) is known to cause drug-induced liver injury (DILI) in humans. Therefore, the detection or prediction of these side-effects at an early stage using appropriate biomarkers is the need of the hour. Micro RNA (miR)-122 is expected to be a novel biomar...

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Bibliographic Details
Published in:	Biological & pharmaceutical bulletin Vol. 41; no. 11; pp. 1732 - 1735
Main Authors:	Munakata, Chie, Fuchigami, Yuki, Hiroishi, Shu, Haraguchi, Ayana, Hagimori, Masayori, Enomoto, Hatsune, Tachiki, Hidehisa, Kodama, Yukinobu, Sasaki, Hitoshi, Kawakami, Shigeru
Format:	Journal Article
Language:	English
Published:	Japan The Pharmaceutical Society of Japan 01-11-2018 Pharmaceutical Society of Japan Japan Science and Technology Agency
Subjects:	5-Fluorouracil Acetaminophen Acetaminophen - adverse effects Alanine Alanine transaminase Alanine Transaminase - blood Analgesics Analgesics, Non-Narcotic - adverse effects Analgesics, Non-Narcotic - therapeutic use Animals Antimetabolites, Antineoplastic - adverse effects Antimetabolites, Antineoplastic - therapeutic use Antineoplastic drugs Antitumor agents biomarker Biomarkers Biomarkers - metabolism Chemical and Drug Induced Liver Injury - diagnosis Chemical and Drug Induced Liver Injury - etiology Chemical and Drug Induced Liver Injury - metabolism Drug dosages Drug interaction Drug interactions Early Diagnosis Fluorouracil - adverse effects Hep G2 Cells Humans Liver Liver - drug effects Liver - metabolism liver injury Male Mice Mice, Inbred C57BL micro RNA-122 MicroRNAs - metabolism Ribonucleic acid RNA Side effects acetaminophen liver injury micro RNA-122 biomarker
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Summary:	Administration of high doses of acetaminophen (APAP) is known to cause drug-induced liver injury (DILI) in humans. Therefore, the detection or prediction of these side-effects at an early stage using appropriate biomarkers is the need of the hour. Micro RNA (miR)-122 is expected to be a novel biomarker for liver injury. However, more evidence is required in various alternate situations such as its use in combination as APAP is often used along with anticancer drugs. In the present study, we aimed to evaluate the functions of miR-122 as a biomarker for liver injury in comparison with alanine aminotransferase (ALT) in a mice model with the APAP-induced liver injury (AILI). Consequently, there was a dose-dependent increase in miR-122 after administration of APAP intraperitoneally. Similar observations were made for ALT activity. Additionally, the expression of miR-122 increased in a more rapid manner compared to ALT activity. However, there was a variation in the miR-122 expression. Further, we investigated the drug–drug interaction between APAP and 5-fluorouracil using miR-122 and ALT in mice. As a result, the degree of AILI was not changed by the use of 5-fluorouracil in combination with APAP in mice.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0918-6158 1347-5215
DOI:	10.1248/bpb.b18-00504