Classification, hepatotoxic mechanisms, and targets of the risk ingredients in traditional Chinese medicine-induced liver injury.

Abstract:

:Traditional Chinese medicine (TCM) has become a crucial cause of drug-induced liver injury (DILI). Differ from chemical medicines, TCM feature more complex and mostly indefinite components. This review aimed to clarify the classification, underlying mechanisms and targets of the risk components in TCM-induced liver injury to further guide the secure application of TCM. Relevant studies or articles published on the PubMed database from January 2008 to December 2019 were searched. Based on the different chemical structures of the risk ingredients in TCM, they are divided into alkaloids, glycosides, toxic proteins, terpenoids and lactones, anthraquinones, and heavy metals. According to whether drug metabolism is activated or hepatocytes are directly attacked during TCM-induced liver injury, the high-risk substances can be classified into metabolic activation, non-metabolic activation, and mixed types. Mechanisms of the hepatotoxic ingredients in TCM-induced hepatotoxicity, including cytochrome P450 (CYP450) induction, mitochondrial dysfunction, oxidative damage, apoptosis, and idiosyncratic reaction, were also summarized. The targets involved in the risk ingredient-induced hepatocellular injury mainly include metabolic enzymes, nuclear receptors, transporters, and signaling pathways. Our periodic review and summary on the risk signals of TCM-induced liver injury must be beneficial to the integrated analysis on the multi-component, multi-target, and multi-effect characteristics of TCM-induced hepatotoxicity.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Pan X,Zhou J,Chen Y,Xie X,Rao C,Liang J,Zhang Y,Peng C

doi

10.1016/j.toxlet.2020.01.026

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

48-56

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(20)30034-5

journal_volume

323

pub_type

杂志文章,评审
  • Predicting dermal permeability of biocides in commercial cutting fluids using a LSER approach.

    abstract::The aim of this study is to predict dermal permeability of four phenolic biocides in four different formulations using a linear solvation energy relationship (LSER) approach, with a calibrated flow through diffusion cell system. Mathematical descriptors were determined in the laboratory, by mathematical computations, ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2007.09.005

    authors: Vijay V,Yeatts JL Jr,Riviere JE,Baynes RE

    更新日期:2007-12-10 00:00:00

  • A new photosafety screening strategy based on in chemico photoreactivity and in vitro skin exposure for dermally-applied chemicals.

    abstract::This study involved an attempt to establish a new photosafety screening system for dermally-applied chemicals consisting of a reactive oxygen species (ROS) assay and an in vitro skin permeation test. The ROS assay was undertaken to evaluate photoreactivity of six test compounds, acridine (ACD), furosemide (FSM), hexac...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2019.09.016

    authors: Iyama Y,Sato H,Seto Y,Onoue S

    更新日期:2019-12-15 00:00:00

  • Genetic differences between C57BL/6 and DBA/2 mice in the inductions of UDP-glucuronyl transferases for 3-hydroxybenzo(a)pyrene, p-nitrophenol, and bilirubin by 3-methylcholanthrene.

    abstract::In C57BL/6 mice, aryl hydrocarbon hydroxylase (AHH) increased 1 day after treatment with 3-methylcholanthrene, and induction of UDP-glucuronyl transferases for 3-hydroxybenzo(a)pyrene, p-nitrophenol and bilirubin in the liver microsomes was observed 2 to 5 days later. In DBA/2 mice, neither AHH nor transferase activit...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(80)90146-0

    authors: Nemoto N,Takayama S

    更新日期:1980-01-01 00:00:00

  • In vitro effects of lead, mercury and cadmium on the enzymic activity of red-blood cell pyrimidine 5'-nucleotidase.

    abstract::The decrease of pyrimidine 5'-nucleotidase (P5N) in human erythrocytes, detected in persons occupationally exposed to lead (Pb), is not an in vitro artefact resulting from the release of lead during erythrocyte hemolysis but is a true reflection of the enzyme activity in vivo. Like Pb, mercury (Hg) and cadmium (Cd) io...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(84)90147-4

    authors: Mohammed-Brahim B,Buchet JP,Bernard A,Lauwerys R

    更新日期:1984-02-01 00:00:00

  • Renal efflux transporter expression in pregnant mice with Type I diabetes.

    abstract::Prior research suggests that sex hormones and metabolic changes, such as obesity and hyperglycemia, can alter renal transporter expression in rodents. The purpose of this study was to characterize the expression of kidney efflux transporters and regulatory transcription factors in response to Type I diabetes and pregn...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2012.04.008

    authors: Yacovino LL,Aleksunes LM

    更新日期:2012-06-20 00:00:00

  • Evaluation of in vitro absorption, decontamination and desorption of organophosphorous compounds from skin and synthetic membranes.

    abstract::Chemical warfare agents, such as soman, and pesticides, such as chlorpyrifos, dichlorvos or malathion, are toxic organophosphorous compounds (OPCs) that are readily absorbed by the skin. Decontamination using solvents or surfactants may modify the cornified layer - the skin's main barrier against xenobiotic penetratio...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2013.03.005

    authors: Mircioiu C,Voicu VA,Ionescu M,Miron DS,Radulescu FS,Nicolescu AC

    更新日期:2013-05-23 00:00:00

  • Differences in elimination rates of methylmercury between two genetic variant strains of mice.

    abstract::This study demonstrates an intraspecies difference in elimination of methylmercury between two genetic variant strains of mice. Following a single non-toxic dose of 203Hg labeled methylmercury (0.5 mg Hg/kg i.p.), the half-time of 203Hg elimination in the CBA/J inbred strain was 7.4 days compared to 3.0 days in the CF...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(80)90114-9

    authors: Kostyniak PJ

    更新日期:1980-10-01 00:00:00

  • Size and site dependent biological hazard potential of particulate matters collected from different heights at the vicinity of a building construction.

    abstract::Although building constructions are a recurring part of urbanization, the health risk of particulate matters (PM) originating from such activities have seldom been subjected to detailed studies. We sought to characterize the relative risk of air borne PM collected from different heights (ground and top floor) of a bui...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2015.08.002

    authors: Li H,Fang CH,Shi W,Gurusamy S,Li S,Krishnan MN,George S

    更新日期:2015-11-04 00:00:00

  • Generic physiologically based kinetic modelling for farm animals: Part I. Data collection of physiological parameters in swine, cattle and sheep.

    abstract::Physiologically based kinetic (PBK) models for farm animals are of growing interest in food and feed safety with key applications for regulated compounds including quantification of tissue concentrations, kinetic parameters and the setting of safe exposure levels on an internal dose basis. The development and applicat...

    journal_title:Toxicology letters

    pub_type: 杂志文章,meta分析

    doi:10.1016/j.toxlet.2019.10.021

    authors: Lautz LS,Dorne JLCM,Oldenkamp R,Hendriks AJ,Ragas AMJ

    更新日期:2020-02-01 00:00:00

  • Characterization of urinary metabolites as biomarkers of colistin-induced nephrotoxicity in rats by a liquid chromatography/mass spectrometry-based metabolomics approach.

    abstract::Colistin is a polypeptide antibiotic that effectively treats infections caused by multidrug-resistant Gram-negative bacteria, but its clinical use is limited due to nephrotoxicity. The purpose of the present study was to identify biomarkers of colistin-induced nephrotoxicity and to further characterize the mechanisms ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2016.02.018

    authors: Jeong ES,Kim G,Moon KS,Kim YB,Oh JH,Kim HS,Jeong J,Shin JG,Kim DH

    更新日期:2016-04-25 00:00:00

  • Manganese exposure induces α-synuclein aggregation in the frontal cortex of non-human primates.

    abstract::Aggregation of α-synuclein (α-syn) in the brain is a defining pathological feature of neurodegenerative disorders classified as synucleinopathies. They include Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Occupational and environmental exposure to manganese (Mn) is asso...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2012.12.006

    authors: Verina T,Schneider JS,Guilarte TR

    更新日期:2013-03-13 00:00:00

  • Pharmacokinetics of obidoxime in patients poisoned with organophosphorus compounds.

    abstract:OBJECTIVES:Reactivation of inhibited acetylcholinesterase (AChE) with oximes is a causal therapy of intoxication with organophosphorus compounds (OPs). Maximal oxime effects are expected when effective doses are administered as soon as possible and as long as reactivation can be anticipated. An obidoxime plasma level i...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2010.06.005

    authors: Thiermann H,Eyer F,Felgenhauer N,Pfab R,Zilker T,Eyer P,Worek F

    更新日期:2010-09-01 00:00:00

  • An endocrine-disrupting chemical, fenvalerate, induces cell cycle progression and collagen type I expression in human uterine leiomyoma and myometrial cells.

    abstract::Fenvalerate (Fen), widely used for its high insecticidal potency and low mammalian toxicity, is classified as an endocrine-disrupting chemical. Recently, Fen has received great attention for its adverse effects on human reproductive health. In this study, we found that Fen (10 microM) had a stimulatory effect on the g...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2010.03.004

    authors: Gao X,Yu L,Castro L,Moore AB,Hermon T,Bortner C,Sifre M,Dixon D

    更新日期:2010-07-15 00:00:00

  • Tellurium-induced cognitive deficits in rats are related to neuropathological changes in the central nervous system.

    abstract::The effects of sodium tellurite 0.1 and 0.4 mg/kg were assessed in the Morris water maze. Two days after treatment rats were tested for acquisition (posttreatment days 3-6) and on seventh day on a spatial retention task. Tellurium treatment was found to cause significant impairment in retention of the spatial learning...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(02)00050-4

    authors: Widy-Tyszkiewicz E,Piechal A,Gajkowska B,Smiałek M

    更新日期:2002-05-28 00:00:00

  • Effects of blowing sand fine particles on plasma membrane permeability and fluidity, and intracellular calcium levels of rat alveolar macrophages.

    abstract::Ambient fine particulate matter (PM2.5, particulates with an aerodynamic diameter < or = 2.5 microm) can suppress alveolar macrophage (AM) functions, but the data concerning the effects of blowing sand PM2.5 on AMs remain limited. The aim of the present study is to investigate the influences of blowing sand PM2.5 on A...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2005.01.010

    authors: Geng H,Meng Z,Zhang Q

    更新日期:2005-06-17 00:00:00

  • Influence of paracetamol (acetaminophen) on cadmium-induced lipid peroxidation in hepatocytes from starved rats.

    abstract::Isolated hepatocytes form thiobarbituric acid (TBA)-reactants, a parameter of lipid peroxidation (LPO), when exposed to cadmium (Cd). Paracetamol (Para) inhibits this response, dependent on time and concentration. Cd-induced SH-group decline, however, and enhanced plasma membrane permeability to Trypan Blue (TB) were ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(83)90210-2

    authors: Müller L

    更新日期:1983-02-01 00:00:00

  • Stimulation of natural killer cell activity by murine retroviral infection and cocaine.

    abstract::The effects of cocaine and murine AIDS on natural killer (NK) cell activity in C57BL/6 mice was studied. Cocaine may play a major role in the development and progression to AIDS in the human population. Chronic intraperitoneal injection of cocaine was shown to cause an increase in NK cell activity over those of saline...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(91)90066-f

    authors: Poet TS,Pillai R,Wood S,Watson RR

    更新日期:1991-12-01 00:00:00

  • N-Acetylcysteine protects inner ear hair cells and spiral ganglion neurons from manganese exposure by regulating ROS levels.

    abstract::Manganese (Mn) is an indispensable cofactor for many enzymes and a basic factor for many reproductive and metabolic pathways. However, exposure to high concentrations of Mn can result in deleterious effects on the central nervous system and peripheral nerves, including nerves associated with the auditory system. Based...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2017.07.903

    authors: Wang W,Li D,Ding X,Zhao Q,Chen J,Tian K,Qiu Y,Lu L

    更新日期:2017-09-05 00:00:00

  • Renal biomarkers predict nephrotoxicity after paraquat.

    abstract::Paraquat is a widely used herbicide which has been involved in many accidental and intentional deaths. Nephrotoxicity is common in severe acute paraquat poisoning. We examined seven renal injury biomarkers, including cystatin-C, kidney injury molecule-1, β2-microglobulin, clusterin, albumin, neutrophil gelatinase-asso...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2013.08.003

    authors: Wunnapuk K,Liu X,Peake P,Gobe G,Endre Z,Grice JE,Roberts MS,Buckley NA

    更新日期:2013-10-09 00:00:00

  • Catalytic bioscavengers in nerve agent poisoning: A promising approach?

    abstract::The repeated use of the nerve agent sarin against civilians in Syria in 2013 emphasizes the continuing threat by chemical warfare agents. Multiple studies demonstrated a limited efficacy of standard atropine-oxime treatment in nerve agent poisoning and called for the development of alternative and more effective treat...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审

    doi:10.1016/j.toxlet.2015.07.012

    authors: Worek F,Thiermann H,Wille T

    更新日期:2016-02-26 00:00:00

  • Acute iron overload leads to hypothalamic-pituitary-gonadal axis abnormalities in female rats.

    abstract::Iron plays a critical role in a mammal's physiological processes. However, iron tissue deposits have been shown to act as endocrine disrupters. Studies that evaluate the effect of acute iron overload on hypothalamic-pituitary-gonadal (HPG) axis health are particularly sparse. This study demonstrates that acute iron ov...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2015.10.027

    authors: Rossi EM,Marques VB,Nunes Dde O,Carneiro MT,Podratz PL,Merlo E,dos Santos L,Graceli JB

    更新日期:2016-01-05 00:00:00

  • Prenatal administration of indomethacin modulates Th2 cytokines in juvenile rats.

    abstract::Indomethacin (IND) suppresses the T-dependent antibody response (TDAR) in juvenile males when it is administered to pregnant rats during late gestation. In this study, the effect of IND on cytokine production in juvenile rats was examined to investigate the mechanism behind the suppression of antibody production. IND ...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2008.11.013

    authors: Kushima K,Sakuma S,Furusawa S,Fujiwara M

    更新日期:2009-02-25 00:00:00

  • Silver nanoparticles down-regulate Nrf2-mediated 8-oxoguanine DNA glycosylase 1 through inactivation of extracellular regulated kinase and protein kinase B in human Chang liver cells.

    abstract::Recently, we reported that silver nanoparticles (AgNPs) induced reactive oxygen species (ROS) generation and the resultant oxidative stress contributes to the cell damage associated with AgNPs. 8-Oxoguanine (8-oxoG) is sensitive marker of ROS-induced DNA damage. 8-Oxoguanine DNA glycosylase 1 (OGG1) is an important DN...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2011.09.002

    authors: Piao MJ,Kim KC,Choi JY,Choi J,Hyun JW

    更新日期:2011-11-30 00:00:00

  • The pentachlorophenol metabolite tetrachloro-p-hydroquinone induces the formation of 8-hydroxy-2-deoxyguanosine in liver DNA of male B6C3F1 mice.

    abstract::Tetrachloro-p-hydroquinone (TCHQ), the major metabolite of pentachlorophenol (PCP) in mammalian systems, is known to autoxidize to its semiquinone radical under physiological conditions. In this way, PCP could present a potent source of reactive oxygen species (ROS) during metabolization. ROS contribute to numerous mo...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(94)90085-x

    authors: Dahlhaus M,Almstadt E,Appel KE

    更新日期:1994-12-01 00:00:00

  • Stimulation of protein kinase A activity and induced terminal differentiation of human skin fibroblasts in culture by low-frequency electromagnetic fields.

    abstract::In the present study experiments are described, which indicate that the exposure of normal human skin fibroblasts (HSFs) to a low-frequency electromagnetic field of 20 Hz and 7-8 mT does induce terminal differentiation within 14 days of daily exposure of 12 h. As demonstrated by the analysis of the expression level of...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(98)00095-2

    authors: Löschinger M,Thumm S,Hämmerle H,Rodemann HP

    更新日期:1998-08-01 00:00:00

  • Inhibition of store-operated Ca(2+) channels prevent ethanol-induced intracellular Ca(2+) increase and cell injury in a human hepatoma cell line.

    abstract::Elevated intracellular Ca(2+) content is implicated in ethanol-induced hepatocyte apoptosis and necrosis. Extracellular Ca(2+) influx has been suggested to play a role in this process. However, the exact Ca(2+)-permeable channel involved in the plasma membrane is still unclear. This study investigated the role of stor...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/j.toxlet.2011.11.007

    authors: Liu H,Jia X,Luo Z,Guan H,Jiang H,Li X,Yan M

    更新日期:2012-02-05 00:00:00

  • Determination of arsenic in urine by atomic absorption spectrophotometry for biological monitoring of occupational exposure to arsenic.

    abstract::An atomic absorption spectrophotometric (AAS) method was successfully applied to analysis of urine for arsenic (As) as a measure of biological monitoring of occupational exposure to As in Vietnam. The application of the method to urine samples from 75 non-exposed control urbanites (after 2-day abstinence from sea food...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/s0378-4274(99)00087-9

    authors: Dang TM,Tran QT,Vu KV

    更新日期:1999-09-05 00:00:00

  • Guanidinoacetic acid (GAA) synthesis in rat tubular suspension as a system for evaluating gentamicin (GM) nephrotoxicity.

    abstract::Since guanidinoacetic acid (GAA), a precursor of creatine, is synthesized mainly in the proximal tubule of the kidney where gentamicin (GM) nephrotoxicity often occurs, GM-induced renal cell damage was investigated using GAA synthesis in tubular suspension as an indicator. Results obtained were as follows: (1) GAA syn...

    journal_title:Toxicology letters

    pub_type: 杂志文章

    doi:10.1016/0378-4274(95)03411-0

    authors: Takeda M,Jung KY,Sekine T,Endou H,Koide H

    更新日期:1995-11-15 00:00:00

  • Role of inflammation in chemical-induced hepatotoxicity.

    abstract::The liver, which is the major organ responsible for the metabolism of drugs and toxic chemicals, is also the primary target organ for many toxic chemicals. Increasing evidence has indicated that inflammatory processes are intimately involved in chemical-induced hepatotoxic processes, and like other inflammatory diseas...

    journal_title:Toxicology letters

    pub_type: 杂志文章,评审

    doi:10.1016/s0378-4274(01)00284-3

    authors: Luster MI,Simeonova PP,Gallucci RM,Bruccoleri A,Blazka ME,Yucesoy B

    更新日期:2001-03-31 00:00:00

  • A new method to evaluate toxicological data reliability in risk assessments.

    abstract::Toxicological data used for risk assessments must undergo an evaluation of reliability. Nevertheless, a reliability evaluation scheme for such data has yet to be established in China. A method termed TRAM (Toxicological data Reliability Assessment Method) was developed to evaluate toxicological data reliability. A que...

    journal_title:Toxicology letters

    pub_type: 共识发展会议,杂志文章

    doi:10.1016/j.toxlet.2019.05.002

    authors: Bian Q,Ping Y,Jun W,Lyu Z,Song Y,Zhang L,Liu Z

    更新日期:2019-09-01 00:00:00