Identification of serum microRNAs as potential toxicological biomarkers for toosendanin-induced liver injury in mice.
Acetaminophen
/ toxicity
Alanine Transaminase
/ metabolism
Animals
Aspartate Aminotransferases
/ metabolism
Biomarkers
/ blood
Chemical and Drug Induced Liver Injury
/ blood
Drugs, Chinese Herbal
/ toxicity
Heterocyclic Compounds, 4 or More Rings
/ toxicity
Liver
/ drug effects
Male
Medicine, Chinese Traditional
/ adverse effects
Mice
Mice, Inbred C57BL
MicroRNAs
/ blood
Monocrotaline
/ toxicity
Random Allocation
Specific Pathogen-Free Organisms
Biomarker
Hepatotoxicity
MicroRNA
Toosendanin
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
18
10
2018
revised:
26
01
2019
accepted:
17
02
2019
pubmed:
8
3
2019
medline:
28
7
2019
entrez:
8
3
2019
Statut:
ppublish
Résumé
Toosendan Fructus is traditionally used as an insecticide or digestive tract parasiticide for treating digestive parasites in China. It is recorded to have little toxicity in Chinese Pharmacopoeia and has been found to cause severe liver injury during clinical practice. This study aims to identify candidate serum microRNAs (miRNAs) as potential toxicological biomarkers for reflecting the hepatotoxicity induced by toosendanin (TSN), which is the main toxic compound isolated from Toosendan Fructus METHODS: Alanine/aspartate aminotransferase (ALT/AST) activities detection and liver histological observation were performed to evaluate the liver injury induced by TSN or other hepatotoxicants in mice. miRNAs chip analysis and Real-time PCR assay were conducted to identify the altered miRNAs in serum from TSN-treated mice RESULTS: The results of serum ALT/AST and liver histological evaluation showed that TSN (10 mg/kg) induced hepatotoxicity in mice. The results of miRNAs chip showed that the expression of 81 serum miRNAs was obviously altered in mice treated with TSN for 12 h, and 22 of them have passed the further validation in serum from mice treated with TSN for both 6 h and 12 h. These 22 miRNAs were supposed to be the candidate toxicological biomarkers for TSN-induced hepatotoxicity with more sensitivity as compared to the alteration of AST or ALT activity. Moreover, the expression of miRNA-122-3p and mcmv-miRNA-m01-4-3p was not only increased in TSN-treated mice, but also increased in mice treated with other hepatotoxicants including acetaminophen (APAP), monocrotaline (MCT) and diosbuibin B (DB). Only the expression of serum miRNA-367-3p was increased in TSN-treated mice but not changed in the liver injury induced by APAP, MCT or DB CONCLUSION: miR-122-3p and mcmv-miRNA-m01-4-3p may be two commonly sensitive biomarkers for reflecting the hepatotoxicity induced by exogenous hepatotoxicants, and miR-367-3p may be a specific biomarker for reflecting the liver injury induced by TSN.
Sections du résumé
BACKGROUND
BACKGROUND
Toosendan Fructus is traditionally used as an insecticide or digestive tract parasiticide for treating digestive parasites in China. It is recorded to have little toxicity in Chinese Pharmacopoeia and has been found to cause severe liver injury during clinical practice.
PURPOSE
OBJECTIVE
This study aims to identify candidate serum microRNAs (miRNAs) as potential toxicological biomarkers for reflecting the hepatotoxicity induced by toosendanin (TSN), which is the main toxic compound isolated from Toosendan Fructus METHODS: Alanine/aspartate aminotransferase (ALT/AST) activities detection and liver histological observation were performed to evaluate the liver injury induced by TSN or other hepatotoxicants in mice. miRNAs chip analysis and Real-time PCR assay were conducted to identify the altered miRNAs in serum from TSN-treated mice RESULTS: The results of serum ALT/AST and liver histological evaluation showed that TSN (10 mg/kg) induced hepatotoxicity in mice. The results of miRNAs chip showed that the expression of 81 serum miRNAs was obviously altered in mice treated with TSN for 12 h, and 22 of them have passed the further validation in serum from mice treated with TSN for both 6 h and 12 h. These 22 miRNAs were supposed to be the candidate toxicological biomarkers for TSN-induced hepatotoxicity with more sensitivity as compared to the alteration of AST or ALT activity. Moreover, the expression of miRNA-122-3p and mcmv-miRNA-m01-4-3p was not only increased in TSN-treated mice, but also increased in mice treated with other hepatotoxicants including acetaminophen (APAP), monocrotaline (MCT) and diosbuibin B (DB). Only the expression of serum miRNA-367-3p was increased in TSN-treated mice but not changed in the liver injury induced by APAP, MCT or DB CONCLUSION: miR-122-3p and mcmv-miRNA-m01-4-3p may be two commonly sensitive biomarkers for reflecting the hepatotoxicity induced by exogenous hepatotoxicants, and miR-367-3p may be a specific biomarker for reflecting the liver injury induced by TSN.
Identifiants
pubmed: 30844585
pii: S0944-7113(19)30038-8
doi: 10.1016/j.phymed.2019.152867
pii:
doi:
Substances chimiques
Biomarkers
0
Drugs, Chinese Herbal
0
Heterocyclic Compounds, 4 or More Rings
0
MIRN367 microRNA, mouse
0
MicroRNAs
0
Mirn122 microRNA, mouse
0
diosbulbin B
20086-06-0
Acetaminophen
362O9ITL9D
Monocrotaline
73077K8HYV
toosendanin
79304-40-8
Aspartate Aminotransferases
EC 2.6.1.1
Alanine Transaminase
EC 2.6.1.2
Types de publication
Journal Article
Langues
eng
Pagination
152867Informations de copyright
Copyright © 2019 Elsevier GmbH. All rights reserved.