Abstract:
:Glycyrrhetinic acid (GA), the main active ingredient of licorice, reportedly has anti-inflammatory and hepatoprotective properties, but its molecular mechanisms remain be elusive. In the present study, Balb/c mice were pretreated with GA (10, 30, or 100mg/kg) 1h before lipopolysaccharide (LPS)/d-galactosamine (D-GalN) administration. In other in vitro experiment, RAW264.7 macrophages were pretreated with GA before LPS exposure. The mortality, hepatic tissue histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Toll like receptor 4 (TLR4), interleukin-1 receptor-associated kinases (IRAKs), activation of mitogen-activated protein kinases (MAPKs) and NF-κB, and production of TNF-α were assessed by flow cytometry, western blotting, and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that pretreatment with GA protected mice against LPS/D-GalN-induced fulminant hepatic failure (FHF), including a dose-dependent alleviation of mortality and ALT/AST elevation, ameliorating hepatic pathological damage, and decreasing TNF-α release. Moreover, GA inhibited LPS-induced activation of MAPKs and NF-κB in response to LPS, but the expression of TLR4 was not affected in vivo and in vitro. Notably, GA pretreatment in vivo suppressed IRAK-1 activity while inducing IRAK-M expression. Silencing of IRAK-M expression with siRNA blocked these beneficial effects of GA on the activation of MAPKs and NF-κB as well as TNF-α production in LPS-primed macrophages. Taken together, we conclude that GA could prevent LPS/D-GalN-induced FHF. The underlying mechanisms may be related to up-regulation of IRAK-M, which in turn caused deactivation of IRAK-1 and subsequent MAPKs and NF-κB, resulting in inhibiting TNF-α production.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Yin X,Gong X,Zhang L,Jiang R,Kuang G,Wang B,Chen X,Wan Jdoi
10.1016/j.taap.2017.02.011subject
Has Abstractpub_date
2017-04-01 00:00:00pages
8-16eissn
0041-008Xissn
1096-0333pii
S0041-008X(17)30068-6journal_volume
320pub_type
杂志文章abstract::Previous work has shown that chlordecone (CD)-amplified CCl4 hepatotoxicity and lethality can be mitigated by pretreatment with cyanidanol. These studies also revealed that stimulated hepatocellular regeneration might play an important role in the cyanidanol protection of CD-amplified CCl4 toxicity. The present studie...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90268-j
更新日期:1991-03-15 00:00:00
abstract::Nanotechnology has the potential to make a beneficial impact on several agricultural, forestry, and environmental challenges, such as urbanization, energy constraints, and sustainable use of resources. However, new environmental and human health hazards may emerge from nano-enhanced applications. This raises concerns ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2017.05.025
更新日期:2017-08-15 00:00:00
abstract::Perfluorooctane sulfonate (PFOS), an emerging persistent contaminant that is commonly encountered during daily life, has been shown to exert toxic effects on the central nervous system (CNS). However, the molecular mechanisms underlying the neurotoxicity of PFOS remain largely unknown. It has been widely acknowledged ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2015.06.012
更新日期:2015-10-15 00:00:00
abstract::Recently, we described a family of non-targeting monomethylauristatin E (MMAE) antibody-drug conjugates (ADCs) whose pharmacokinetics could be tuned through incorporation of a short polyethylene glycol (PEG) moiety of up to twelve units into a drug-linker to render the ADC surface more hydrophilic. That work demonstra...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2020.114932
更新日期:2020-04-01 00:00:00
abstract::Metabolism of tert-butyl hydroperoxide (TBHP, 2.0 mM) by glutathione peroxidase within isolated rat hepatocytes caused a rapid oxidation of intracellular reduced glutathione and ultimately NADPH through glutathione reductase. TBHP also caused the formation of surface blebs in the hepatocyte plasma membrane followed by...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(86)90267-x
更新日期:1986-07-01 00:00:00
abstract::Many environmental contaminants can disrupt the adaptive immune response. Exposure to the ubiquitous aryl hydrocarbon receptor (AhR) ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other agonists suppresses the antibody response. The underlying pathway mechanism by which TCDD alters B cell function is not well u...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.01.015
更新日期:2013-04-01 00:00:00
abstract::The physiologically based dosimetry description for acrylonitrile (ACN) and its mutagenic epoxide metabolite 2-cyanoethylene oxide (CEO) in F-344 rats (M. L. Gargas, M. E. Anderson, S.K.O. Teo, R. Batra, T. R. Fennell, and G. L. Kedderis, 1995, Toxicol. Appl. Pharmacol. 134, 185-194) has been refined to include a phys...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.0239
更新日期:1996-10-01 00:00:00
abstract::Exposure protocols were designed to ask whether lung damage in rats exposed to either ozone or nitrogen dioxide is proportional to dose rate or to cumulative dose. Thus, the response of rats to a constant product of concentration of oxidant air pollutant and time of exposure (C x T) was evaluated for 3-day exposures o...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(92)90281-v
更新日期:1992-01-01 00:00:00
abstract::Numbers of engineered nanomaterials (ENMs) are steadily increasing. Therefore, alternative testing approaches with reduced costs and high predictivity suitable for high throughput screening and prioritization are urgently needed to ensure a fast and effective development of safe products. In parallel, extensive resear...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.01.019
更新日期:2016-05-15 00:00:00
abstract::Methylmercury (MeHg) is an environmental neurotoxicant which induces neuropathological changes in both the central nervous and peripheral sensory nervous systems. Our recent study demonstrated that down-regulation of Ras-related C3 botulinum toxin substrate 1 (Rac1), which is known to promote neuritic extension, prece...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.09.011
更新日期:2011-01-01 00:00:00
abstract::Male rats were injected SC with 0.6 mg Cd/kg/day for 5 days per week for 2, 4, 6, and 8 weeks. Liver and kidney were examined morphologically and analyzed for metallothionein, cadmium, zinc, and copper. Morphologic changes were found in kidney but not in liver. The earliest ultrastructural change consisted of myelin f...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(89)90272-x
更新日期:1989-11-01 00:00:00
abstract::The influence of carbon monoxide (CO) on the development of systemic hypertension was studied in Dahl rats selectively bred for susceptibility (DS) and resistance (DR) to NaCl-induced hypertension. This study was designed to examine the interactions among rat line (DS or DR), NaCl content of diet, and exposure to CO. ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90003-6
更新日期:1984-11-01 00:00:00
abstract::Increased incidence of mortality and morbidity due to cardiopulmonary complications has been found to associate with elevated levels of particulate air pollution (particulate matter with an aerodynamic diameter < 10 microm, PM10 and <2.5 microm, PM2. 5). Lung injury and an imbalance of inflammatory mediators are propo...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1998.8591
更新日期:1999-03-15 00:00:00
abstract::Colchicine-specific antibody (IgG(C] was tested in mice for reversal of colchicine toxicity. The mouse model was chosen because it reflects human pathophysiology in colchicine poisoning. IgG(C) was administered when at least 85% of colchicine was distributed in tissues. It resulted in a dramatic decrease in lethality ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(90)90172-q
更新日期:1990-07-01 00:00:00
abstract::A study was undertaken to determine whether alterations in the gene expression or overt histological signs of neurotoxicity in selected regions of the forebrain might occur from acrylamide exposure via drinking water. Gene expression at the mRNA level was evaluated by cDNA array and/or RT-PCR analysis in the striatum,...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.07.036
更新日期:2009-11-01 00:00:00
abstract::Carcinogenic chromium (VI) compounds are persistent environmental contaminants with potential for human exposure through drinking water. One lesion associated with chromium (VI) exposure is the formation of DNA-protein crosslinks (DPC). In an attempt to develop markers of chromium exposure, the formation of DPC in lym...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90191-g
更新日期:1991-06-01 00:00:00
abstract::The DDT metabolite 3-methylsulfonyl-DDE (3-MeSO(2)-DDE) has been proposed as a lead compound for an improved adrenocortical carcinoma (ACC) treatment. ACC is a rare malignant disorder with poor prognosis, and the current pharmacological therapy o,p'-DDD (mitotane) has limited efficacy and causes severe adverse effects...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.10.018
更新日期:2010-02-01 00:00:00
abstract::The effect of butylated hydroxytoluene (BHT), which is used widely as an antioxidant, on IgE-dependent allergic responses in vivo and in vitro was investigated. For in vivo study, passive cutaneous anaphylaxis (PCA) was elicited in rats by i.d. injection of anti-DNP IgE and 48 h later by i.v. injection of DNP-HSA. BHT...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2007.05.007
更新日期:2007-09-01 00:00:00
abstract::Carnosic acid (CA), a major bioactive component in rosemary extract, has many biological and pharmaceutical activities. Smad3 acetylation can regulate the transcription of type I α2 collagen (COL1A2), which is the major component of the extracellular matrix (ECM). The aim of the current study was to evaluate whether C...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2017.12.010
更新日期:2018-01-15 00:00:00
abstract::Triclosan (TCS) is an antimicrobial agent commonly found in a variety of personal care products and cosmetics. TCS readily enters the environment through wastewater and is detected in human plasma, urine, and breast milk due to its widespread use. Studies have implicated TCS as a disruptor of thyroid and estrogen sign...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.08.013
更新日期:2016-10-01 00:00:00
abstract::Our recent study demonstrated the increased risk of renal cell carcinoma (RCC) associated with high urinary total arsenic levels among people living in a low arsenic exposure area. Genomic instability is important in arsenic carcinogenesis. This study evaluated the relationship between the polymorphisms of p53, p21, a...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.09.018
更新日期:2011-12-15 00:00:00
abstract::Arsenic is a ubiquitous metalloid element present in both inorganic and organic forms in the environment. The liver is considered to be a primary organ of arsenic biotransformation and methylation, as well as the main target of arsenic toxicity. Studies have confirmed that Chang human hepatocytes have an efficient ars...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2021.115404
更新日期:2021-01-09 00:00:00
abstract::A number of chemicals cause a nephrotoxic syndrome in male rats, referred to as protein droplet or alpha 2u-globulin (alpha 2u) nephropathy. To evaluate the potential human risk for developing a similar chemically-induced protein-mediated nephrotoxic response, the low-molecular-weight protein fraction (LMWPF) was isol...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1993.1064
更新日期:1993-04-01 00:00:00
abstract::Oxidative stress is involved in hepatic stellate cells (HSCs) activation and extracellular matrix overproduction. We previously reported the promising effects of dioscin against CCl4-induced liver fibrosis, but its effects and mechanisms on BDL- and DMN-induced liver fibrosis remain unknown. The results in the present...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2015.12.024
更新日期:2016-02-01 00:00:00
abstract::Chlorinated dibenzo-p-dioxins (CDDs) are a series of mono- to octa-chlorinated homologous chemicals commonly referred to as polychlorinated dioxins. One of the most potent, well-known, and persistent member of this family is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). As part of translational research to make computer...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2016.12.007
更新日期:2017-01-15 00:00:00
abstract::To assess the relevance of previously identified axonal atrophy to hexanedione neuropathy, the present study quantitated fiber size in peripheral nerve of rats intoxicated with 2,5-hexanedione (HD) by either oral ingestion (0.4% in drinking water) or ip injection (0.4 g/kg/day). Prior to the appearance of neurobehavio...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1995.1208
更新日期:1995-11-01 00:00:00
abstract::MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.06.014
更新日期:2012-09-01 00:00:00
abstract::Contact sensitization is caused by low molecular weight compounds which penetrate the skin and bind to protein. In many cases, these compounds are activated to reactive species, either by autoxidation on exposure to air or by metabolic activation in the skin. Geraniol, a widely used fragrance chemical, is considered t...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.08.014
更新日期:2008-12-01 00:00:00
abstract::The Fhit tumor suppressor protein possesses Ap(3)A (diadenosine triphosphate - ApppA) hydrolytic activity in vitro and its gene is found inactive in many pre-malignant states due to gene inactivation. For several years Fhit has been a widely investigated protein as its cellular function still remains largely unsolved....
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2009.08.023
更新日期:2009-12-01 00:00:00
abstract::Isoprene (2-methyl-1,3-butadiene), a volatile monomer occurring in the natural environment and used in the manufacture of elastomers, is a close chemical relative of the animal carcinogen 1,3-butadiene. To obtain toxicokinetic data for inhaled isoprene, male F344 rats were exposed in groups of 30 to 14C-labeled isopre...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90044-5
更新日期:1987-06-30 00:00:00