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 CA inhibits COL1A2 transcription via the reduction of Smad3 acetylation against liver fibrosis. The results showed that CA treatment significantly suppressed COL1A2 transcription and markedly decreased the deposition of ECM induced by dimethylamine (DMN) in rats. Importantly, the suppression of COL1A2 transcription following CA treatment depended on the reduction of Smad3 acetylation via the activation of Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide+ (NAD+)-dependent deacetylase. SIRT1 siRNA increased the acetylation of Smad3 and blocked CA-down-regulated Smad3 deacetylation. Notably, CA-mediated AMP-activated protein kinase-α1 (AMPKα1) activation not only increased AMPKα1 phosphorylation but also increased SIRT1 expression, thus leading to a significant reduction in Smad3 acetylation. Furthermore, CA-mediated SIRT1 activation was inhibited by AMPKα1 siRNA. Collectively, CA can inhibit the transcription of COL1A2 through SIRT1-mediated Smad3 deacetylation, and the activation of SIRT1 by CA involves the AMPKα1/SIRT1 pathway in liver fibrosis.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Zhao Y,Shi X,Ding C,Feng D,Li Y,Hu Y,Wang L,Gao D,Tian X,Yao Jdoi
10.1016/j.taap.2017.12.010subject
Has Abstractpub_date
2018-01-15 00:00:00pages
172-180eissn
0041-008Xissn
1096-0333pii
S0041-008X(17)30491-Xjournal_volume
339pub_type
杂志文章abstract::In the present study we have examined the effects of hydrocarbons on the formation of reactive oxygen species (ROS) in human neutrophil granulocytes in vitro. We found that hydrocarbons induce ROS formation in a concentration-dependent manner and that the ROS-inducing potency increases with increasing number of carbon...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/s0041-008x(03)00158-3
更新日期:2003-07-15 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::Protein phosphatase 2A (PP2A) is a serine-threonine phosphatase that regulates cell signaling pathways. Its inactivation is correlated with tumor malignancy, possibly due to the effects on cell differentiation and malignant cell transformation. Therefore, it has been noted that PP2A could be a promising target for can...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2017.10.009
更新日期:2017-12-01 00:00:00
abstract::Some environmental chemicals exhibit estrogenic or antiandrogenic activity. Some of these, such as bisphenol A (bis A) and octylphenols, are used in large amounts in many applications. We have analyzed the effects of bis A and octylphenols on steroidogenesis in Leydig cells by measuring the LH receptor-mediated cAMP a...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1999.8674
更新日期:1999-06-15 00:00:00
abstract::Arsenite is a toxicant and environmental pollutant associated with multisite neoplasias and other health effects. The wide range of doses used and the claims that some high doses are "not toxic" in some assays have confounded studies on its mechanism of action. The purpose of this study is to determine whether the tre...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2004.06.010
更新日期:2005-01-01 00:00:00
abstract::The purpose of this study was to determine whether exposure to levels of sarin causing no overt clinical signs would cause more subtle, adverse health effects that persisted after the exposure ended. Inhalation exposures of male Fischer 344 rats to 0, 0.2, or 0.4 mg/m(3) of sarin for 1 h/day for 1, 5, or 10 days under...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:
更新日期:2002-10-15 00:00:00
abstract::Arsenic-induced side effects limit its application in the treatment of acute promyelocytic leukemia (APL). We recently demonstrated that AS3MT 14215 (rs3740390) genotypes were associated with urinary arsenic metabolites and hematological and biochemical values. To further decipher the role of AS3MT genotypes on arseni...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2019.114687
更新日期:2019-09-15 00:00:00
abstract::A microtiter hemolytic assay was utilized to determine sodium azide (NaN3) modulation of B6C3F1 and C3H mouse serum complement levels in vivo and in vitro. Functional complement was expressed in CH50 units per milliliter. Experiments were performed to determine the in vitro effect of NaN3 on complement mediated lysis ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(84)90108-x
更新日期:1984-05-01 00:00:00
abstract::A group of alkyl epoxides was compared for their guinea pig sensitization capacity and reactivities towards a protein-surrogate substrate, n-butylamine. Instead of the previously reported use of a titration method for determination of alkylation rate, proton nuclear magnetic resonance spectrometry (1H NMR) was used. T...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(91)90094-u
更新日期:1991-05-01 00:00:00
abstract::Many environmental chemicals and drugs negatively affect human health through deleterious effects on mitochondrial function. Currently there is no chemical library of mitochondrial toxicants, and no reliable methods for predicting mitochondrial toxicity. We hypothesized that discrete toxicophores defined by distinct c...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.06.014
更新日期:2013-10-15 00:00:00
abstract::Melatonin is a neuroendocrine hormone which is currently receiving considerable attention as a treatment for jet lag, a treatment for insomnia and, by some, a possible "magic bullet" for delaying the effects of aging and preventing cancer. Production of melatonin is focused primarily in the pineal gland with very wide...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8247
更新日期:1997-11-01 00:00:00
abstract::Two members of the cytochrome P450 2A subfamily, CYP2A10 and 2A11, are abundant nasal enzymes previously characterized in rabbit olfactory microsomes. Rabbit CYP2A is active toward a number of nasal toxicants, including the rat nasal procarcinogen hexamethylphosphoramide (HMPA). While P450s immunochemically related to...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.7975
更新日期:1997-01-01 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::Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. New BPD is characterized as having alveolar simplification. We reported previously that aryl hydrocarbon receptor (AhR) deficiency increased susceptibility to hyperoxic lung injury in adult mice, and this was associated ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.01.003
更新日期:2013-03-15 00:00:00
abstract::Juvenile rat toxicity studies with the direct renin inhibitor aliskiren were initiated to support treatment in the pediatric population. In Study 1, aliskiren was administered orally to juvenile rats at doses of 0, 30, 100 or 300 mg/kg/day with repeated dosing from postpartum day (PPD) 8 to PPD 35/36. In-life, clinica...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2013.12.019
更新日期:2014-02-15 00:00:00
abstract::This study assessed the role of aryl hydrocarbon receptor (AHR) affinity, and cytochrome P4501A (CYP1A) protein and activity in polyaromatic hydrocarbon (PAH)-induced oxidative stress. In the 1-100nM concentration range benzo[a]pyrene (BaP) but not benzo[e]pyrene (BeP) competitively displaced 2nM [(3)H]2, 3, 7, 8-tetr...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2011.04.015
更新日期:2011-07-01 00:00:00
abstract::The effects of the cytochrome P450 inducer beta-naphthoflavone (BNF) on NO2 toxicity were studied in two strains of mice. In one strain (C57B1/6J), cytochrome P450 could be induced by the aromatic hydrocarbon, while in the other strain (DBA/2J) cytochrome P450 was not inducible by this compound. Mice were treated with...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90122-6
更新日期:1988-04-01 00:00:00
abstract::The organophosphate cholinesterase inhibitor soman produced a dramatic increase in arterial blood pressure of up to 60 mm Hg in the unanesthetized rat with variable changes in heart rate. Pretreatment with clonidine resulted in a dose-related inhibition of soman-induced cardiovascular changes and enhanced the time of ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(88)90364-x
更新日期:1988-09-30 00:00:00
abstract::Organic UV filters including benzophenone-3 (BP-3) are widely used to protect humans and materials from damage by UV irradiation. Despite the environmental occurrence of BP-3 in the aquatic environment, little is known about its effects and modes of action. In the present study we assess molecular and physiological ef...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2012.06.008
更新日期:2012-09-01 00:00:00
abstract::Human exposure to certain natural and man-made chemical carcinogens is one of the major risk factors for cancer development. The effect of chemical carcinogens on genetic and epigenetic alterations and their significance in the development of cancer has been well-established. In contrast, the role of microRNAs (miRNAs...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.taap.2015.11.013
更新日期:2016-12-01 00:00:00
abstract::A case study was conducted, using dibutyl phthalate (DBP), to explore an approach to using toxicogenomic data in risk assessment. The toxicity and toxicogenomic data sets relative to DBP-related male reproductive developmental outcomes were considered conjointly to derive information about mode and mechanism of action...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2010.09.006
更新日期:2013-09-15 00:00:00
abstract::Arsenic is an environmental pollutant that has been associated with an increased risk for the development of cancer and several other diseases through alterations of cellular homeostasis and hepatic function. Cytochrome P450 (P450) modification may be one of the factors contributing to these disorders. Several reports...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2008.11.009
更新日期:2009-09-01 00:00:00
abstract::The physicochemical complexity of airborne particulate matter (PM) has hampered identifying a specific mechanism(s) for its toxicity. In this study, selected physicochemical characteristics (i.e., size, particle number, acidity, and surface charge) were measured on various field PM, derived from urban ambient (St. Lou...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.2001.9341
更新日期:2002-02-01 00:00:00
abstract::Eicosanoids released after ozone exposure of a human bronchial epithelial cell line, BEAS-S6, were analyzed by high-pressure liquid chromatography (HPLC) of supernatants from exposed cells prelabeled with [3H]arachidonic acid. BEAS cells released thromboxane B2 (TxB2), prostaglandin E2 (PGE2), leukotriene C4 (LTC4), L...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1993.1027
更新日期:1993-02-01 00:00:00
abstract::Toxicological and biochemical effects of muconaldehyde, a six-carbon diene dialdehyde, were evaluated in 6- to 9-week-old CD-1 male mice. The LD50 of trans,trans-muconaldehyde was 6.7 and 7.1 mg/kg body wt when calculated by two different methods. Administration of trans,trans-muconaldehyde (2 mg/kg, ip) daily for 10 ...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(85)90396-5
更新日期:1985-09-30 00:00:00
abstract::Tattooing is a popular cosmetic practice involving more than 45 million US citizens. Since the toxicology of tattoo inks and pigments used to formulate tattoo inks has not been reported, we studied the immunological impact of tattooing and determined recovery time from this trauma. SKH-1 hairless mice were tattooed us...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2005.04.003
更新日期:2005-12-01 00:00:00
abstract::Dantrolene is an effective antagonist of anesthesia-induced malignant hyperthermia due to a poorly understood action on skeletal muscle. The present study examines whether the red blood cell can be used as a model to investigate the mechanism of dantrolene action. Halothane (4.7 mM) caused 9% hemolysis of red blood ce...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/0041-008x(87)90133-5
更新日期:1987-09-30 00:00:00
abstract::The antioxidant N-acetyl-L-cysteine (NAC) has been increasingly used as an experimental tool to assess involvement of reactive oxygen species in cell signaling and is being evaluated as a preventive and therapeutic agent for cancer and pulmonary diseases related to inflammation and oxidative stress. However, a detaile...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1997.8361
更新日期:1998-04-01 00:00:00
abstract::Free gold nanoparticles easily aggregate when the environment conditions change. Here, gold nanoparticles (AuNPs) with average diameter of 3.7 nm were prepared and then modified with poly(ethylene glycol) (PEG) to improve stability. The gold nanoparticles were first surface-modified with 3-mercaptopropionic acid (MPA)...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1016/j.taap.2009.03.009
更新日期:2009-06-01 00:00:00
abstract::Cannabinoid receptor (CB) expression was characterized in immunological cell and tissue preparations. Northern analysis revealed approximately 6-kb transcripts for CB1 (brain-type) in mouse spleen and brain and in rat cerebellum. CB1 was not detected in mouse thymus or rat spleen RNA by Northern analysis. CB2 (periphe...
journal_title:Toxicology and applied pharmacology
pub_type: 杂志文章
doi:10.1006/taap.1996.8034
更新日期:1997-02-01 00:00:00