Fluorofenidone attenuates diabetic nephropathy and kidney fibrosis in db/db mice.

Abstract:

BACKGROUND/AIMS:Fluorofenidone [1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone, AKF-PD], a novel pyridone agent, showed potent antifibrotic properties. The aim of the present study was to investigate the effects of AKF-PD on diabetic nephropathy and kidney fibrosis, and to obtain an insight into its mechanisms of action. METHODS:We administered AKF-PD to diabetic db/db mice for 12 weeks. Moreover, we performed in vitro cultures using murine mesangial cells exposed to high ambient glucose concentrations. RESULTS:AKF-PD reduced renal hypertrophy, mesangial matrix expansion and albuminuria in the db/db mice. The upregulated expression of α₁(I)- and α₁(IV)-collagen and fibronectin mRNAs, transforming growth factor-β1 (TGF-β₁), α-smooth muscle actin (α-SMA), and tissue inhibitors of metalloproteinase 1 (TIMP-1) mRNAs and proteins was inhibited by AKF-PD treatment in the renal cortex of db/db mice. The maximal effective dose of AKF-PD was about 500 mg/kg body weight. AKF-PD inhibited the upregulated expression of α₁(I)- and α₁(IV)-collagens, TGF-β₁, TIMP-1 and α-SMA induced by high glucose concentrations in cultured mesangial cells. CONCLUSIONS:Our data indicate that AKF-PD diminishes the abnormal accumulation of mesangial matrix through the inhibition of upregulated expression of TGF-β target genes in kidneys of db/db mice, resulting in attenuation of renal fibrosis and amelioration of renal dysfunction despite persistent hyperglycemia. Therefore, AKF-PD, a potent antifibrotic agent, holds great promise in the treatment of diabetic nephropathy.

journal_name

Pharmacology

journal_title

Pharmacology

authors

Wang LH,Liu JS,Ning WB,Yuan QJ,Zhang FF,Peng ZZ,Lu MM,Luo RN,Fu X,Hu GY,Wang ZH,Tao LJ

doi

10.1159/000329419

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

88-99

issue

1-2

eissn

0031-7012

issn

1423-0313

pii

000329419

journal_volume

88

pub_type

杂志文章
  • Mechanisms of tetraethylammonium-induced contraction in the canine coronary artery.

    abstract::Tetraethylammonium chloride (TEA) at concentrations over 10(-3) mol/l produced a concentration-dependent contraction in the isolated canine coronary artery. We investigated mechanisms of the contractile response and the effects of various vasodilators on the contraction. While phentolamine, propranolol, guanethidine, ...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000138224

    authors: Nishio M,Kigoshi S,Muramatsu I

    更新日期:1986-01-01 00:00:00

  • Novel thiazolidinones as potent anti-inflammatory and analgesic agents.

    abstract::Various new butyridenyl-2-hydroxybenzylidenyl-1,3-thiazolidinones were synthesized and characterized by elemental analyses, IR and PMR spectral data. The compounds were evaluated for their ability to afford protection against inflammation by carrageenin-induced oedema and cotton pellet implantation in albino rats of e...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000138130

    authors: Tandon M,Kumar P,Pande K,Bhalla TN,Barthwal JP

    更新日期:1985-01-01 00:00:00

  • Evidence of nonlinear pharmacokinetics of methotrexate in the rat.

    abstract::Three doses (0.31, 3.1 and 31 mg/kg) of methotrexate (MTX) were given intravenously to rats. The resulting concentration-time curves in plasma (normalized by dividing the plasma concentration by a multiple of the dose) were not superimposable, indicating nonlinear plasma pharmacokinetics. In liver, kidney, bone marrow...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000137723

    authors: Scheufler E

    更新日期:1982-01-01 00:00:00

  • Influence of blood flow on intestinal absorption of xenobiotics.

    abstract::The dependence of intestinal absorption of xenobiotics on the blood flow rate increases from blood flow independent to blood flow limited absorption as the absorbability of the substances increases. Since the absorbed substances are mainly drained by the blood flowing through the subepithelial vessels, not only the to...

    journal_title:Pharmacology

    pub_type: 杂志文章,评审

    doi:10.1159/000137409

    authors: Winne D

    更新日期:1980-01-01 00:00:00

  • Amunine (ovine CRF), urotensin I and sauvagine, three structurally-related peptides, produce selective dilation of the mesenteric circulation.

    abstract::Three synthetic peptides, urotensin I, sauvagine and ovine CRF, have less than 50% sequence homology. In the dog, all three produce selective mesenteric dilation, which appears to be solely responsible for a decrease in peripheral resistance and systemic arterial blood pressure. Urotensin I and sauvagine were found to...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000137732

    authors: MacCannell KL,Lederis K,Hamilton PL,Rivier J

    更新日期:1982-01-01 00:00:00

  • Analysis of the effects of halothane on Gi-coupled muscarinic M2 receptor signaling in Xenopus oocytes using a chimeric G alpha protein.

    abstract::Metabotropic G protein-coupled receptors have recently been recognized as targets for anesthetics and analgesics. In particular, G(q)-coupled receptors such as muscarinic M(1) receptors (M(1)R) and 5-hydroxytryptamine (5-HT) type 2A receptors have been reported to be targets for anesthetics. Much less is known, howeve...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000080106

    authors: Minami K,Uezono Y,Shiraishi M,Okamoto T,Ogata J,Horishita T,Taniyama K,Shigematsu A

    更新日期:2004-11-01 00:00:00

  • Interferon-alpha 2b increases fibrolysis in fibrotic livers from bile duct ligated rats: possible participation of the plasminogen activator.

    abstract::Interferons are known to prevent liver collagen by an antifibrogenic mechanism that involves mRNA procollagen regulation. The aim of the present work was to determine whether interferon could also decrease collagen by increasing its degradation. Fibrosis was induced in male Wistar rats by double ligation and section o...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000139345

    authors: Rodríguez-Fragoso L,González MP,Muriel P

    更新日期:1995-12-01 00:00:00

  • Antihypertensive effect of 5-HT1A agonist buspirone and 5-HT2B antagonists in experimentally induced hypertension in rats.

    abstract::We investigated the antihypertensive effect of 5-HT1A agonist (buspirone) and 5-HT2B antagonists (SB204741 and SB200646) in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. Experiments were divided into two sets: in the first set, sham-operated control and DOCA-treated hypertensive rats received busp...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000082114

    authors: Shingala JR,Balaraman R

    更新日期:2005-03-01 00:00:00

  • Tissue distribution of primaquine in the rat.

    abstract::The distribution of primaquine was measured in seven rat tissues at 15-180 min after the intraperitoneal injection of the antimalarial 8-aminoquinoline. The half-life of unmetabolized primaquine was 4.0 h in lung, 1.7-1.9 h in blood, spleen, kidney and heart, and 1.2 h in liver. At each interval, the concentrations of...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000137508

    authors: Holbrook DJ Jr,Griffin JB,Fowler L,Gibson BR

    更新日期:1981-01-01 00:00:00

  • Evaluation of antiulcer activity of delta9-tetrahydrocannabinol in the Shay rat test.

    abstract::delta9-Tetrahydrocannabinol (THC) inhibited ulcer formation in the pylorus-ligated rat (Shay rat test). However, this antiulcer activity of THC was substantially less than for the anticholinergic substance tridihexethyl chloride both in terms of degree of activity and potency. In addition, the results of the present s...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000136851

    authors: Sofia RD,Diamantis W,Harrison JE,Melton J

    更新日期:1978-01-01 00:00:00

  • Pharmacokinetics of drugs in rabbits with experimental acute renal failure.

    abstract::Serum protein binding and serum levels of antipyrine, phenytoin and phenylbutazone were measured in rabbits with acute renal failure induced by uranyl nitrate. The kinetics of antipyrine are not altered in the uraemic rabbit. Serum protein binding of phenytoin and phenylbutazone is decreased and the volume of distribu...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000136871

    authors: Van Peer A,Belpaire F,Bogaert M

    更新日期:1978-01-01 00:00:00

  • Efficacy and safety of prolonged-release trazodone in major depressive disorder: a multicenter, randomized, double-blind, flexible-dose trial.

    abstract:OBJECTIVE:To investigate the efficacy, safety, and clinical benefit of prolonged-release trazodone (Trittico) in the treatment of major depressive disorder (MDD). METHODS:In this study, 363 Chinese patients with MDD were randomized 1:1 to receive either prolonged-release trazodone (150-450 mg) or placebo treatment for...

    journal_title:Pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1159/000368559

    authors: Zhang L,Xie WW,Li LH,Zhang HG,Wang G,Chen DC,Cao Y,Cui LJ,Zhang KR,Shi JG,Tan QR,Zheng HB,Xu XF,Cheng ZH,Zhao JP

    更新日期:2014-01-01 00:00:00

  • Modulation of urokinase-type plasminogen activator by transforming growth factor beta1 in acetaldehyde-activated hepatic stellate cells.

    abstract::The aim of this study was to determine whether transforming growth factor-beta1 (TGF-beta1) induces the synthesis, release and gene expression of urokinase-type plasminogen activator (uPA) in hepatic stellate cells. In addition to stimulating collagen production, TGF-beta1 induced the morphological and phenotypical ch...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000081071

    authors: Pérez-Liz G,Flores-Hernández J,Arias-Montaño JA,Reyes-Esparza JA,Rodríguez-Fragoso L

    更新日期:2005-01-01 00:00:00

  • Anti-inflammatory activity of thymol: inhibitory effect on the release of human neutrophil elastase.

    abstract::Elastase, a serine proteinase released by activated human neutrophils, can degrade a wide variety of biomacromolecules including elastin, and is considered a marker of inflammatory diseases. As the logical strategy to protect tissue is to inhibit excessive elastase activity, experimental and clinical researches have c...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000093790

    authors: Braga PC,Dal Sasso M,Culici M,Bianchi T,Bordoni L,Marabini L

    更新日期:2006-01-01 00:00:00

  • Effects of triamterene and its phase I and phase II metabolities on sodium transport of the isolated frog skin.

    abstract::We studied the effects of triamterene (TA) on its phase I and phase II metabolites, p-hydroxytriamterene (OH-TA) and p-hydroxytriamterene sulfuric acid ester (OH-TA ester), on sodium transport in the isolated frog skin. While TA applied to the inside (corial side) surface had no effects on potential difference (PD) an...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000137543

    authors: Kramer HJ,Rörig M,Völger KD

    更新日期:1981-01-01 00:00:00

  • The gastrointestinal pharmacology of cannabinoids: focus on motility.

    abstract::The marijuana plant Cannabis sp. and its derivatives and analogues, known as cannabinoids (CBs), induce many effects throughout the whole body. Herein we briefly review the gastrointestinal (GI) pharmacology of CBs, with special focus on motor function. Some drugs are available to treat nausea and emesis, and evidence...

    journal_title:Pharmacology

    pub_type: 杂志文章,评审

    doi:10.1159/000339072

    authors: Abalo R,Vera G,López-Pérez AE,Martínez-Villaluenga M,Martín-Fontelles MI

    更新日期:2012-01-01 00:00:00

  • Prevention of galactosamine-induced hepatotoxicity in rats with fructose-1,6-diphosphate.

    abstract::Galactosamine (GalN) administration produces hepatitis-like liver injury in animals. The hepatotoxicity of GalN is attenuated by several interventions, including activation of the reticuloendothelial system (RES). Fructose-1,6-diphosphate (FDP) administration significantly increases the phagocytic activity of the RES ...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000138861

    authors: Markov AK,Farias LA,Bennett WS,Subramony C,Mihas AA

    更新日期:1991-01-01 00:00:00

  • Pre- and postsynaptic mechanisms involved in tetanic fade induced by pancuronium in the isolated rat muscle.

    abstract::The mechanisms underlying the fade of the tetanic contraction induced by pancuronium were studied in vitro by means of myographical and electrophysiological techniques in the extensor digitorum longus muscle of the rat. Pancuronium (0.5 mumol/l) induced a complete fade of the tetanic contraction while leaving the twit...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000139242

    authors: Gallacci M,Oliveira AC

    更新日期:1994-10-01 00:00:00

  • Cellular uptake of the tyrosine kinase inhibitors imatinib and AMN107 in gastrointestinal stromal tumor cell lines.

    abstract::Imatinib and AMN107 are protein tyrosine kinase inhibitors which reduce KIT autophosphorylation with similar potency. This report describes the cellular uptake of these compounds in two human gastrointestinal stromal tumor (GIST)-derived cell lines (GIST882 and GIST GDG1), which both express constitutively activated K...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000091943

    authors: Prenen H,Guetens G,de Boeck G,Debiec-Rychter M,Manley P,Schoffski P,van Oosterom AT,de Bruijn E

    更新日期:2006-01-01 00:00:00

  • Postjunctional localization of substance P receptors on the rat portal vein.

    abstract::A dose-dependent contractile effect of substance P (SP) on the isolated, everted rat portal vein was competitively inhibited by two selective SP antagonists (pro2, phe7, trp9)-SP and (pro4, trp7,9)-SP 4-11. Phentolamine, atropine, methysergide, mepyramine, cimetidine, Sar1, Ile8-angiotensin II, Leu8, des-Arg9-bradykin...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000137885

    authors: Mastrangelo D,Mathison R,Huggel H

    更新日期:1983-01-01 00:00:00

  • Self-administration of both ethanol and nicotine in rats.

    abstract::Self-administration of either nicotine (NIC) or ethanol (ETH) has been extensively studied. This study addressed for the first time the self-administration of both substances when offered together. Male and female rats of different ages were offered NIC and ETH using the two- or three-bottle free-choice method. When N...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000067801

    authors: Marshall CE,Dadmarz M,Hofford JM,Gottheil E,Vogel WH

    更新日期:2003-03-01 00:00:00

  • Effects of magnesium on human umbilical arteries: role of intracellular calcium stores.

    abstract::The purpose of this investigation on human umbilical arteries was: (1) to analyze the effects of magnesium (Mg2+) in the prevention of contractions induced by 5-hydroxytryptamine (5-HT), KCl, Bay K 8644 and BaCl2; (2) to determine whether the presence of Mg2+ could modulate the response to caffeine in Ca2+-free medium...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000028255

    authors: Tiritilli A

    更新日期:1998-12-01 00:00:00

  • Inhibition effect of curcumin on TNF-α and MMP-13 expression induced by advanced glycation end products in chondrocytes.

    abstract:AIMS:Accumulation of advanced glycation end products (AGEs) plays a pivotal role in the mechanism by which aging contributes to osteoarthritis (OA). In the present study, we examined the effect of curcumin, a pharmacologically safe phytochemical agent, on AGE-induced tumor necrosis factor-α (TNF-α) and matrix metallopr...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000345345

    authors: Yang Q,Wu S,Mao X,Wang W,Tai H

    更新日期:2013-01-01 00:00:00

  • Effect of captopril on urinary kallikrein, blood pressure and myocardial hypertrophy in diabetic spontaneously hypertensive rats.

    abstract::We investigated the total urinary kallikrein levels, left-ventricular wall thickness and mean arterial blood pressure of nontreated and captopril-treated diabetic and nondiabetic spontaneously hypertensive rats. The mean arterial blood pressure was significantly elevated in diabetic spontaneously hypertensive rats as ...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000056171

    authors: Sharma JN,Kesavarao U

    更新日期:2002-04-01 00:00:00

  • The Alcohol Intolerance Produced by Isoniazid Is Not Due to a Disulfiram-Like Reaction Despite Aldehyde Dehydrogenase Inhibition.

    abstract:BACKGROUND/AIMS:Isoniazid (ISO) has been reported to inhibit the hepatic aldehyde dehydrogenase (ALDH) and to cause a disulfiram (DIS)-like reaction, albeit there are no reports demonstrating increased blood acetaldehyde levels after co-administration of ISO with alcohol. The aim of our study was to clarify whether the...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000448759

    authors: Karamanakos PN,Pappas P,Boumba V,Vougiouklakis T,Marselos M

    更新日期:2016-01-01 00:00:00

  • GPR35 is a target of the loop diuretic drugs bumetanide and furosemide.

    abstract::We report that the loop diuretic drugs bumetanide and furosemide used in the treatment of hypertension are GPR35 agonists. We utilized calcium flux, inositol phosphate accumulation, and dynamic redistribution assays to examine the pharmacology of these compounds on the human, mouse and rat GPR35. While potent on human...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000335127

    authors: Yang Y,Fu A,Wu X,Reagan JD

    更新日期:2012-01-01 00:00:00

  • The Inhibitory Effect of S-777469, a Cannabinoid Type 2 Receptor Agonist, on Skin Inflammation in Mice.

    abstract::We investigated the effects of S-777469 (1-[[6-Ethyl-1-[4-fluorobenzyl]-5-methyl-2-oxo-1, 2-dihydropyridine-3-carbonyl]amino]-cyclohexanecarboxylic acid), a novel cannabinoid type 2 receptor (CB2) agonist, on 1-fluoro-2,4-dinitrobenzene (DNFB)-induced ear inflammation and mite antigen-induced dermatitis in mice. The o...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000455916

    authors: Haruna T,Soga M,Morioka Y,Imura K,Furue Y,Yamamoto M,Hayakawa J,Deguchi M,Arimura A,Yasui K

    更新日期:2017-01-01 00:00:00

  • Effects of cyclic adenosine monophosphate-dependent protein kinase and calcium-dependent protein kinase modulators on stimulated gastric acid secretion in the perfused rat stomach.

    abstract::The effects of cyclic adenosine monophosphate-dependent protein kinase (PKA) and calcium-dependent protein kinase (PKC) modulators on secretagogue-stimulated gastric acid secretion were studied in the continuously perfused stomach of the anesthetized rat. Intravenous histamine (0.25 mg/kg/h) and pentagastrin (2 microg...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000139368

    authors: Rotker JD,Strapko A,Nandi J,Bosche MC,Levine RA

    更新日期:1995-10-01 00:00:00

  • Interaction of probenecid with the protein binding of methotrexate.

    abstract::The effect of probenecid on the plasma protein binding of methotrexate (MTX) has been examined in vitro. At concentrations greater than or equal to 5 x 10(-4) M, probenecid caused a significant reduction (greater than 30%) in the plasma binding of MTX. It is suggested that in vivo this would lead to a greater dispersi...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000137947

    authors: Paxton JW

    更新日期:1984-01-01 00:00:00

  • Influence of the 2'-chloro substitution on central activity of desmethyldiazepam.

    abstract::Two diazepam derivatives, the N-desmethyl and the 2'-chlor-N-desmethyldiazepam, were compared in rats using behavioral and EEG techniques. Both drugs had depressant effects upon locomotor activity, facilitated behavior suppressed by punishment, increased the number of shocks received by rats in a Sidman avoidance proc...

    journal_title:Pharmacology

    pub_type: 杂志文章

    doi:10.1159/000136845

    authors: Babbini M,Gaiardi M,Bartoletti M

    更新日期:1978-01-01 00:00:00