Abstract:
:Three important features must be considered when proposing therapeutic strategies in liver cirrhosis: inflammation, oxidative stress and fibrogenesis. Pirfenidone is a synthetic molecule which oxidative action has not been tested in cirrhosis. Cirrhosis was induced in rats by ligation of the common bile duct or carbon tetrachloride (CCl(4)) chronic intoxication and treated with pirfenidone or diphenyleneiodonium (a potent known antioxidant) for the last two weeks for bile duct ligation model or for the last three weeks for CCl(4) chronic intoxication. A 60% reduction in fibrosis index for bile duct ligation model and 42% for CCl(4) along with reduced inflammation was observed. Considerable reduction on hepatic enzymes and total and direct bilirubins were detected with pirfenidone in both models. Pirfenidone antioxidant capacity rendered a 28% and 30% reduction in nitrites and malonyldealdehide concentration in bile duct ligation and 52% and 38% in CCl(4). With respect to gene expression, fibrotic genes like transforming growth factor-beta (TGF-beta) and collagen Ialpha (Col-1alpha) were down-regulated by pirfenidone and increased expression of regenerative genes like hepatocyte growth factor (HGF) and c-met . Superoxide dismutase (SOD), catalase (CAT) and inducible nitric oxide synthase (iNOS) gene expression were importantly down-regulated where nuclear factor kappa B (NF-kappaB) binding activity also decreased with pirfenidone treatment. Also, SOD and CAT functional activity decreased after pirfenidone action. On the other hand, diphenyleneiodonium induced a drop in oxidative stress similar in extent to pirfenidone, but it was not as effective as pirfenidone in reducing fibrosis. In this work, we showed antioxidant properties of pirfenidone beyond its well-known antifibrotic effect. These features make pirfenidone an attractive drug for trying fibrotic diseases accompanied by oxidative stress processes.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Salazar-Montes A,Ruiz-Corro L,López-Reyes A,Castrejón-Gómez E,Armendáriz-Borunda Jdoi
10.1016/j.ejphar.2008.06.110subject
Has Abstractpub_date
2008-10-24 00:00:00pages
69-77issue
1-3eissn
0014-2999issn
1879-0712pii
S0014-2999(08)00716-4journal_volume
595pub_type
杂志文章abstract::To investigate whether argatroban ((2R,4R)-4-methyl-1-[N(2)-((RS)-3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidinecarboxylic acid hydrate, a selective thrombin inhibitor, exerts a direct action on phenotype conversion of vascular smooth muscle cells, cultured rabbit aortic vascular smooth muscl...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(03)01293-7
更新日期:2003-02-07 00:00:00
abstract::Adjuvant-induced arthritis is associated with body weight loss and decreased pituitary growth hormone (GH) and hepatic insulin-like growth factor-I (IGF-I) synthesis. Cytokines as tumor necrosis factor (TNF) mediate wasting associated with chronic inflammation. The aim of this study was to analyse whether the inhibiti...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2006.02.035
更新日期:2006-04-24 00:00:00
abstract::Several recent reports have demonstrated a role for selective cannabinoid CB2 receptor agonists in pain modulation, showing both analgesic and antihyperalgesic activities. While the mechanism of action is poorly understood, it has been postulated that these effects may be indirect, involving release of endogenous opio...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2005.10.043
更新日期:2005-12-28 00:00:00
abstract::In neutrophils and several other phagocytes, a pertussis and cholera toxin-sensitive guanine nucleotide-binding protein (G-protein) couples the receptors for formyl methionine-containing chemotactic peptides to stimulation of phospholipase C. We used membranes of myeloid-differentiated HL 60 cells to study the role of...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(89)90031-x
更新日期:1989-12-05 00:00:00
abstract::Mitochondria play a central role in cell biology not only as producers of ATP, but also in the sequestration of Ca(2+) and the generation of free radicals. They are also repositories of several proteins which regulate apoptosis. Perturbations in the normal functions of mitochondria will inevitably disturb cell functio...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/s0014-2999(02)01842-3
更新日期:2002-07-05 00:00:00
abstract::Although convulsions due to local anesthetic systemic toxicity are thought to be due to inhibition of GABA(A) receptor-linked currents in the central nervous system, the mechanism of action remains unclear. We therefore examined the effects of local anesthetics on gamma-aminobutyric acid (GABA)-induced currents using ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(00)00463-5
更新日期:2000-08-11 00:00:00
abstract::G(s)α is a ubiquitously expressed G protein α-subunit that couples receptors to the generation of intracellular cyclic AMP. The G(s)α gene GNAS is a complex gene that undergoes genomic imprinting, an epigenetic phenomenon that leads to differential expression from the two parental alleles. G(s)α is imprinted in a tiss...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2010.10.105
更新日期:2011-06-11 00:00:00
abstract::We investigated the effects of ginsenosides, the active ingredient of ginseng, on neuronal or muscle-type nicotinic acetylcholine receptor channel activity expressed in Xenopus oocytes after injection of cRNA encoding bovine neuronal alpha3beta4, alpha7 or human muscle alphabetadeltavarepsilon subunits. Treatment with...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(02)01508-x
更新日期:2002-05-03 00:00:00
abstract::The effects of GABA and diazepam on the spontaneous and potassium-evoked release of 3H-5-HT from rat hippocampal synaptosomes, preloaded by incubation with 3H-5-HT, have been investigated. Both GABA and diazepam independently increased the spontaneous release of 5-HT whereas they blocked the calcium-dependent, potassi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(80)90054-0
更新日期:1980-11-07 00:00:00
abstract::The thromboxane A2/prostaglandin endoperoxide (TXA2/PGH2) receptor antagonist activity of CV-4151, a potent TXA2 synthetase inhibitor, was examined. CV-4151 inhibited guinea pig and human platelet aggregation induced by U-44069 with IC50 values of 1.2 +/- 0.3 X 10(-5) and 1.9 +/- 0.4 X 10(-5) M, respectively, and inhi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(88)90169-0
更新日期:1988-03-15 00:00:00
abstract::In incubation medium containing Na+ as the only cation, the specific binding of [3H]cocaine to a membrane preparation obtained from rat striatum reached a maximal level for 10 mM Na+, whereas higher concentrations decreased its affinity. The specific binding of [3H]cocaine was inhibited monophasically by GBR 12783, ma...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(94)90188-0
更新日期:1994-07-15 00:00:00
abstract::The actions of a purified Helicobacter pylori lipopolysaccharide (3 mg x kg(-1), i.v.) on rat gastric antral and duodenal microvascular integrity (determined as radiolabelled albumin leakage) and the expression of the inducible nitric oxide (NO) synthase (iNOS; assessed by the citrulline assay) were investigated 4 h a...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01008-1
更新日期:2001-05-25 00:00:00
abstract::Inhibition of the thromboxane A2-synthesizing enzyme (DP-1904: [+/-]-6-[1-imidazolylmethyl]-5,6,7,8-tetrahydronaphthalene-2-carbo xylic acid hydrochloride hemihydrate) reportedly suppresses intercellular adhesion molecule-1 (ICAM-1) expression on the surface of stimulated vascular endothelial cells (Ishizuka et al., 1...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(96)00478-5
更新日期:1996-10-03 00:00:00
abstract::Free radical production contributes to the early ischemic response and the neuroinflammatory response to injury initiates the second wave of cell death following ischemic stroke. Edaravone is a free radical scavenger, and borneol has shown anti-inflammatory effect. We investigated the synergistic effect of these two d...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2014.06.035
更新日期:2014-10-05 00:00:00
abstract::Nitric oxide (NO) is present in the exhaled breath of humans and other mammalian species. It is generated in the lower airways by enzymes of the nitric oxide synthase (NOS) family, although nonenzymatic synthesis and consumptive processes may also influence levels of NO in exhaled breath. The biological properties of ...
journal_title:European journal of pharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.ejphar.2005.12.069
更新日期:2006-03-08 00:00:00
abstract::An iron-free diet for 28 days caused a reduced level of iron in the blood. Iron deficient rats exhibited a lower level of motor activity and reversed circadian rhythms of thermoregulation and motor activity. The hypothermic effect of d-amphetamine was significantly reduced in iron deficient rats, and the magnitude of ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(81)90048-0
更新日期:1981-09-24 00:00:00
abstract::Hypovolemic shock was produced in rats by withdrawing about 50% of the estimated total blood volume. Following mean arterial pressure stabilization in the range of 22-23 mm Hg, the rats were given an i.v. bolus injection of L-6-ketopiperidine-2-carbonyl-L-leucyl-L-proline amide (RGH-2202) to be compared with thyrotrop...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(90)90511-4
更新日期:1990-06-21 00:00:00
abstract::Transient ischemia was produced for 15 min by occlusion of the middle cerebral artery in halothane-anesthetized rats, and changes in the extracellular concentrations of neurotransmitter monoamines and amino acids were examined in the striatum. The occlusion produced marked increases in the extracellular concentrations...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2003.11.006
更新日期:2004-01-26 00:00:00
abstract::The human ether-a-go-go-related gene (hERG) cardiac K(+) channels are one of the representative pharmacological targets for development of drugs against cardiovascular diseases such as arrhythmia. Panax ginseng has been known to have cardio-protective effects. However, little is known about the molecular mechanisms of...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.05.006
更新日期:2011-08-01 00:00:00
abstract::The binding of the bisquaternary muscarine receptor antagonist heptane-1,7-bis(dimethyl-3'-phthalimidopropyl)-ammonium bromide (C7/3-phth) was investigated at a number of cholinergic binding sites using (-)-[3H]nicotine, [3H]pirenzepine and (-)-[3H]quinuclidinyl benzilate ([3H]QNB) in both central and peripheral tissu...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0922-4106(93)90002-q
更新日期:1993-06-15 00:00:00
abstract::Central monoaminergic neurotransmitters have been implicated in the control of food intake in different animal species but it remains unclear whether these same neurochemical systems effectively regulate feeding behaviour in the genetically obese (ob/ob) mouse. Neuropharmacological studies have demonstrated, for examp...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(93)90778-g
更新日期:1993-03-02 00:00:00
abstract::We synthesized the o-, m- and p-bromo derivatives of dl-threo-methylphenidate from the corresponding bromophenylacetonitriles by modification of the literature synthesis of methylphenidate (Panizzon, Helv. Chim. Acta 1944, 27, 1748). In in vitro binding assays all three dl-threo bromo compounds had higher affinities t...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(94)00460-9
更新日期:1994-10-24 00:00:00
abstract::The ability of putative melatonin receptor antagonists to antagonise melatonin-induced aggregation of pigment granules in cultured neural crest Xenopus laevis melanophores was examined. Neither ML 23 (N-(2,4-dinitrophenyl)-5-methoxytryptamine) nor 6-methoxy-2-benzoxazolinone showed agonist or antagonist activity. N-Ac...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(92)90629-i
更新日期:1992-03-31 00:00:00
abstract::Chronic infection with the liver fluke, Opisthorchis viverrini, induces advanced periductal fibrosis and is a relative risk factor for cholangiocarcinoma in Southeastern Asia. We examined the reducing effect of curcumin on hepatobiliary fibrosis using O. viverrini-infected hamsters supplemented with dietary 1% curcumi...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2010.04.018
更新日期:2010-07-25 00:00:00
abstract::The effects of tacrine (5 mg/kg i.p.) in lithium chloride (LiCl; 12 mEq/kg i.p.)-pretreated (24 h beforehand) animals and of kainate (10 mg/kg i.p.) on brain citrulline, the co-product of nitric oxide (NO) synthesis, were studied in rats. High performance liquid chromatography analysis of whole brain tissue homogenate...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/0014-2999(95)00689-3
更新日期:1995-12-27 00:00:00
abstract::The suppression of pro-inflammatory cytokine-induced inflammation responses is an attractive pharmacological target for the development of therapeutic strategies for inflammatory bowel disease (IBD). In the present study, we evaluated the anti-inflammatory properties of flavonoid isoliquiritigenin (ISL) in intestinal ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2016.12.026
更新日期:2017-02-05 00:00:00
abstract::Huperzine A, a promising therapeutic agent for Alzheimer's disease, was examined for its potential to antagonize the deleterious neurochemical, structural, and cognitive effects of infusing beta-amyloid protein-(1-40) into the cerebral ventricles of rats. Daily intraperitoneal administration of huperzine A for 12 cons...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(01)01030-5
更新日期:2001-06-15 00:00:00
abstract::We have previously demonstrated that the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has an antinociceptive effect on various pain stimuli in a naloxone-reversible manner. In the present study, the role of the endogenous opioid peptide β-endorphin in DHA-induced antinociception was examined. DHA-induced ...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2011.05.047
更新日期:2011-09-01 00:00:00
abstract::This study investigates the possible protective effects of levocetirizine against fructose-induced insulin resistance, hepatic steatosis and vascular dysfunction, in comparison to pioglitazone, a standard insulin sensitizer. Male Sprague Dawley rats (150-200 g) were divided into 4 groups. Three groups were fed on high...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/j.ejphar.2014.07.021
更新日期:2014-10-05 00:00:00
abstract::YM992 ((S)-2-[[(7-fluoro-4-indanyl)oxy]methyl]morpholine monohydrochloride) is a novel compound that has selective serotonin (5-hydroxytryptamine, 5-HT) re-uptake inhibition and 5-HT2A receptor antagonistic activity in vivo. YM992, fluoxetine and citalopram showed 5-HT uptake inhibition activity in l-5-hydroxy-tryptop...
journal_title:European journal of pharmacology
pub_type: 杂志文章
doi:10.1016/s0014-2999(97)10108-x
更新日期:1997-06-18 00:00:00