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  1 / 3187 MEDLINE  
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[PMID]:28466691
[Au] Autor:Guha M; Nguyen L; Poitout-Belissent F; Bedard A; Raman K
[Ad] Endereço:1 Medivation, Inc, San Francisco, CA, USA.
[Ti] Título:Salt Selection Matters: Differential Renal Toxicity With MDV1634.Maleate Versus MDV1634.2HCl.
[So] Source:Int J Toxicol;36(3):207-219, 2017 May/Jun.
[Is] ISSN:1092-874X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Salt forms of pharmaceutical compounds can have unique pharmacokinetic and toxicity properties. MDV1634 was evaluated for neurology indication and also demonstrated blood pressure (BP)-lowering effects in nonclinical studies. During the chemistry manufacturing campaign, 2 salt forms, dihydrochloride (2HCl) and maleate (MAL), which improved chemical stability and water solubility of the free base were identified. MDV1634.MAL showed better chemical attributes and was evaluated in toxicology studies for further development. A 28-day oral toxicity study in dogs with MDV1634.MAL demonstrated partially reversible renal toxicity. Although MAL salt is generally regarded as safe, renal toxicity is sometimes observed in rats and dogs. To evaluate contribution of each salt form to renal toxicity and BP lowering, an additional 28-day study was conducted with MDV1634.2HCL and MDV1634.MAL, which included toxicokinetics, continuous BP measurement in a subset of dogs, and sensitive urinary biomarker evaluation for temporal monitorability and reversibility of potential renal findings. In the repeat study, both salt forms showed similar exposures during the dosing period, but renal tubular toxicity was observed only with MDV1634.MAL and not with MDV1634.2HCl. The renal findings with MDV1634.MAL included early urinary biomarker changes (increase in albumin, clusterin, ß2 microglobulin, and neutrophil gelatinase-associated lipocalin); elevations in serum blood urea nitrogen and creatinine; and microscopic findings of partially reversible tubular basophilia, single cell necrosis, pigmentation, and mineralization. The renal findings in contrast to the BP findings were MAL-specific and considered not related to MDV1634, thereby under scoring the importance of salt forms in pharmaceutical development.
[Mh] Termos MeSH primário: Rim/efeitos dos fármacos
Maleatos/toxicidade
[Mh] Termos MeSH secundário: Animais
Pressão Sanguínea/efeitos dos fármacos
Cães
Feminino
Rim/patologia
Masculino
Maleatos/farmacocinética
Sais/farmacocinética
Sais/toxicidade
Testes de Toxicidade Subaguda
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Maleates); 0 (Salts)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1177/1091581817704379


  2 / 3187 MEDLINE  
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[PMID]:29073142
[Au] Autor:Wu C; Chen HC; Chen ST; Chiang SY; Wu KY
[Ad] Endereço:Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taipei, Taiwan.
[Ti] Título:Elevation in and persistence of multiple urinary biomarkers indicative of oxidative DNA stress and inflammation: Toxicological implications of maleic acid consumption using a rat model.
[So] Source:PLoS One;12(10):e0183675, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Maleic acid (MA), an intermediate reagent used in many industrial products, instigated public health concerns in Taiwan when it was used to adulterate an array of starch-based delicacies to improve texture and storage time. Established studies reported that exposure to high concentrations of MA induce renal injury; little is known whether oxidative stress is induced at a relative low dose. This study aims to investigate the effect of oral single dose exposure of MA on the status of oxidative stress and inflammation. Single dose of MA at 0, 6 and 60 mg/kg (control, low- and high-dose groups, respectively) were orally administered to adult male and female rats. Urine samples were collected and analyzed to measure 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-IsoPGF2α), 8-nitroguanine (8-NO2Gua) and N-acetyl-S-(tetrahydro-5-hydroxy-2-pentyl-3-furanyl)-L-cysteine (HNE-MA) using LC-MS/MS. Results revealed that oral consumption of MA induced oxidative DNA damage and lipid peroxidation, as demonstrated by the statistically significant increases in urinary levels of 8-NO2Gua, 8-OHdG, and 8-isoPGF2α, in high-dosed male rats within 12 h of oral gavage (p < 0.05). Additionally, increases in concentration of these biomarkers persist for days after consumption; male rats appear to be more sensitive to oxidative burden compared to their counterparts. The aforementioned findings could help elucidate the mechanisms through which nephrotoxicity occur.
[Mh] Termos MeSH primário: Biomarcadores/urina
Dano ao DNA
Modelos Animais de Doenças
Inflamação/urina
Maleatos/toxicidade
Estresse Oxidativo
[Mh] Termos MeSH secundário: Animais
Peso Corporal/efeitos dos fármacos
Feminino
Masculino
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Maleates); 91XW058U2C (maleic acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171027
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183675


  3 / 3187 MEDLINE  
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[PMID]:28923687
[Au] Autor:Dominguez Pardo JJ; Dörr JM; Renne MF; Ould-Braham T; Koorengevel MC; van Steenbergen MJ; Killian JA
[Ad] Endereço:Membrane Biochemistry & Biophysics, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Padualaan 8, 3584 CH Utrecht, The Netherlands. Electronic address: j.j.dominguezpardo@uu.nl.
[Ti] Título:Thermotropic properties of phosphatidylcholine nanodiscs bounded by styrene-maleic acid copolymers.
[So] Source:Chem Phys Lipids;208:58-64, 2017 Nov.
[Is] ISSN:1873-2941
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Styrene-maleic acid copolymers (SMA) have been gaining interest in the field of membrane research due to their ability to solubilize membranes into nanodics. The SMA molecules act as an amphipathic belt that surrounds the nanodiscs, whereby the hydrophobic styrene moieties can insert in between the lipid acyl chains. Here we used SMA variants with different styrene-to-maleic acid ratio (i.e. 2:1, 3:1 and 4:1) to investigate how lipid packing in the nanodiscs is affected by the presence of the polymers and how it depends on polymer composition. This was done by analyzing the thermotropic properties of a series of saturated phosphatidylcholines in nanodiscs using laurdan fluorescence and differential scanning calorimetry. In all cases it was found that the temperature of the main phase transition (T ) of the lipids in the nanodiscs is downshifted and that its cooperativity is strongly reduced as compared to the situation in vesicles. These effects were least pronounced for lipids in nanodiscs bounded by SMA 2:1. Unexpected trends were observed for the calorimetric enthalpy of the transition, suggesting that the polymer itself contributes, possibly by rearranging around the nanodiscs when the lipids adopt the fluid phase. Finally, distinct differences in morphology were observed for nanodiscs at relatively high polymer concentrations, depending on the SMA variant used. Overall, the results suggest that the extent of preservation of native thermodynamic properties of the lipids as well as the stability of the nanodiscs at high polymer concentrations is better for SMA 2:1 than for the other SMA variants.
[Mh] Termos MeSH primário: Maleatos/química
Nanoestruturas/química
Fosfatidilcolinas/química
Poliestirenos/química
Temperatura Ambiente
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Maleates); 0 (Phosphatidylcholines); 0 (Polystyrenes); 25300-64-5 (styrene-maleic acid polymer)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE


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[PMID]:28705644
[Au] Autor:Fukuda T; Goto R; Kiho T; Ueda K; Muramatsu S; Hashimoto M; Aki A; Watanabe K; Tanaka N
[Ad] Endereço:Rare Disease & LCM Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: fukuda.takeshi.zv@daiichisankyo.co.jp.
[Ti] Título:Discovery of DS79182026: A potent orally active hepcidin production inhibitor.
[So] Source:Bioorg Med Chem Lett;27(16):3716-3722, 2017 08 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. Inhibition of hepcidin could be a strategy favorable to treating anemia of chronic disease (ACD). We report herein the synthesis and structure-activity relationships (SARs) of a series of benzisoxazole compounds as orally active hepcidin production inhibitors. The optimization study of multi kinase inhibitor 1 led to a potent and bioavailable hepcidin production inhibitor 38 (DS79182026), which showed serum hepcidin lowering effects in a mouse IL-6 induced acute inflammatory model.
[Mh] Termos MeSH primário: Benzoxazóis/química
Benzoxazóis/farmacologia
Carbamatos/química
Carbamatos/farmacologia
Hepcidinas/antagonistas & inibidores
[Mh] Termos MeSH secundário: Administração Oral
Animais
Benzoxazóis/administração & dosagem
Benzoxazóis/farmacocinética
Carbamatos/administração & dosagem
Carbamatos/farmacocinética
Regulação da Expressão Gênica/efeitos dos fármacos
Meia-Vida
Hepcidinas/genética
Hepcidinas/metabolismo
Inflamação/induzido quimicamente
Inflamação/tratamento farmacológico
Concentração Inibidora 50
Interleucina-6
Maleatos/administração & dosagem
Maleatos/química
Maleatos/farmacocinética
Maleatos/farmacologia
Camundongos
Camundongos Endogâmicos C57BL
Microssomos Hepáticos/efeitos dos fármacos
Microssomos Hepáticos/metabolismo
Modelos Animais
Inibidores de Proteínas Quinases/administração & dosagem
Inibidores de Proteínas Quinases/química
Inibidores de Proteínas Quinases/farmacocinética
Inibidores de Proteínas Quinases/farmacologia
RNA Mensageiro/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Benzoxazoles); 0 (Carbamates); 0 (DS79182026); 0 (Hepcidins); 0 (Interleukin-6); 0 (Maleates); 0 (Protein Kinase Inhibitors); 0 (RNA, Messenger); 6ET4K804XA (benzmalecene)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE


  5 / 3187 MEDLINE  
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[PMID]:28624590
[Au] Autor:Mahmud JA; Hasanuzzaman M; Nahar K; Rahman A; Hossain MS; Fujita M
[Ad] Endereço:Laboratory of Plant Stress Responses, Department of Applied Biological Science, Faculty of Agriculture, Kagawa University, Miki-cho, Kita-gun, Kagawa 761-0795, Japan; Department of Agroforestry and Environmental Science, Faculty of Agriculture, Sher-e-Bangla Agricultural University, Sher-e-Bangla Na
[Ti] Título:Maleic acid assisted improvement of metal chelation and antioxidant metabolism confers chromium tolerance in Brassica juncea L.
[So] Source:Ecotoxicol Environ Saf;144:216-226, 2017 Oct.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Chromium (Cr) is a highly toxic environmental pollutant that negatively affects plant growth and development. Thus, remediating Cr from soil or increasing plant tolerance against Cr stress is urgent. Organic acids are recognized as agents of phytoremediation and as exogenous protectants, but using maleic acid (MA) to attain these results has not yet been studied. Therefore, our study investigated the effects of MA on Cr uptake and mitigation of Cr toxicity. We treated 8-d-old Indian mustard (Brassica juncea L.) seedlings with Cr (0.15mM and 0.3mM K CrO , 5 days) alone and in combination with MA (0.25mM) in a semi-hydroponic medium. Under Cr stress, plants accumulated Cr in both the roots and shoots in a dose-dependent manner, where the roots showed higher accumulation. Chromium stress reduced the growth and biomass of the Indian mustard plants by reducing water status and photosynthetic pigments, and increased oxidative damage due to generation of toxic reactive oxygen species (ROS) and methylglyoxal (MG). Chromium stress also interfered with the function of the antioxidant defense and glyoxalase systems. However, using MA in the Cr-stressed plants further increased Cr uptake in the roots, but it slightly reduced the translocation of Cr from the roots to the shoots at a lower dose of Cr and significantly at a higher dose. Moreover, MA also increased the other non-protein thiols (NPTs) containing phytochelatin (PC) content of the seedlings, which reduced Cr toxicity. Supplementing the stressed plants with MA upregulated the non-enzymatic antioxidants (ascorbate, AsA; glutathione, GSH); the activities of the enzymatic antioxidants including ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT); and the enzymes of the glyoxalase system including glyoxalase I (Gly I) and glyoxalase II (Gly II); and finally reduced oxidative damage and increased the chlorophyll content and water status as well the growth and biomass of the plants. Our findings suggested two potential uses of MA: first, enhancing phytoremediation, principally phytostabilization and second, working as an exogenous protectant to enhance Cr tolerance.
[Mh] Termos MeSH primário: Antioxidantes/metabolismo
Cromo/toxicidade
Maleatos/farmacologia
Mostardeira/efeitos dos fármacos
Estresse Oxidativo/efeitos dos fármacos
Poluentes do Solo/toxicidade
[Mh] Termos MeSH secundário: Adaptação Fisiológica
Biodegradação Ambiental
Biomassa
Cromo/metabolismo
Mostardeira/crescimento & desenvolvimento
Mostardeira/metabolismo
Poluentes do Solo/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Maleates); 0 (Soil Pollutants); 0R0008Q3JB (Chromium); 91XW058U2C (maleic acid)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170619
[St] Status:MEDLINE


  6 / 3187 MEDLINE  
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[PMID]:28515158
[Au] Autor:Helwa I; Choudhary V; Chen X; Kaddour-Djebbar I; Bollag WB
[Ad] Endereço:Charlie Norwood VA Medical Center (V.C., X.C., I.K.-D., W.B.B.), Augusta, Georgia; Department of Oral Biology (I.H., W.B.B.), Department of Physiology (V.C., X.C., I.K.-D., W.B.B.), and Department of Medicine (Dermatology) (W.B.B.), Medical College of Georgia, Augusta University, Augusta, Georgia.
[Ti] Título:Anti-Psoriatic Drug Monomethylfumarate Increases Nuclear Factor Erythroid 2-Related Factor 2 Levels and Induces Aquaporin-3 mRNA and Protein Expression.
[So] Source:J Pharmacol Exp Ther;362(2):243-253, 2017 Aug.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Oxidative stress contributes to inflammatory skin diseases, including psoriasis. Monomethylfumarate (MMF) is an antipsoriatic agent with a poorly understood mechanism of action. In other cell types MMF increases the expression of nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor that regulates cellular antioxidant responses, to reduce oxidative stress like that observed in inflammatory disorders such as multiple sclerosis. We tested the hypothesis that MMF enhances Nrf2 activity in keratinocytes, thereby improving their capacity to counteract environmental stresses. We used Western analysis, immunofluorescence, and real-time quantitative reverse-transcription polymerase chain reaction to examine the effect of MMF on the expression of Nrf2 and its targets. We also measured intracellular reactive oxygen species (ROS) levels following MMF treatment. Our data show that MMF increased total and nuclear Nrf2 levels in primary mouse keratinocytes and enhanced mRNA expression of several Nrf2-downstream effectors, including heme oxygenase-1 and peroxiredoxin-6. Moreover, MMF treatment attenuated the generation of ROS following hydrogen peroxide treatment. On the other hand, the expression and membranous localization of aquaporin-3 (AQP3), a glycerol channel implicated in keratinocyte differentiation, was stimulated by MMF, which also enhanced keratinocyte glycerol uptake. The Nrf2 activator sulforaphane also increased AQP3 levels, suggesting that AQP3 expression may be regulated by Nrf2. We show for the first time that MMF stimulates Nrf2 and AQP3 expression and function/activity in keratinocytes. This effect may account, in part, for the previously observed ability of MMF to inhibit proliferation and inflammatory mediator production and promote differentiation in keratinocytes and to treat psoriasis.
[Mh] Termos MeSH primário: Aquaporina 3/biossíntese
Fumaratos/farmacologia
Maleatos/farmacologia
Fator 2 Relacionado a NF-E2/biossíntese
Psoríase
RNA Mensageiro/biossíntese
[Mh] Termos MeSH secundário: Animais
Animais Recém-Nascidos
Aquaporina 3/agonistas
Aquaporina 3/genética
Sequência de Bases
Células Cultivadas
Expressão Gênica
Queratinócitos/efeitos dos fármacos
Queratinócitos/metabolismo
Camundongos
Fator 2 Relacionado a NF-E2/agonistas
RNA Mensageiro/agonistas
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aqp3 protein, mouse); 0 (Fumarates); 0 (Maleates); 0 (NF-E2-Related Factor 2); 0 (Nfe2l2 protein, mouse); 0 (RNA, Messenger); 0RQ6CXO9KD (citraconic acid); 158801-98-0 (Aquaporin 3)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE
[do] DOI:10.1124/jpet.116.239715


  7 / 3187 MEDLINE  
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[PMID]:28384213
[Au] Autor:Yang KL; Chang WT; Hong MY; Hung KC; Chuang CC
[Ad] Endereço:Department of Animal Science, National Pei-men Senior Agricultural and Industrial Vocational School, Tainan, Taiwan.
[Ti] Título:Prevention of TGF-ß-induced early liver fibrosis by a maleic acid derivative anti-oxidant through suppression of ROS, inflammation and hepatic stellate cells activation.
[So] Source:PLoS One;12(4):e0174008, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Current anti-fibrotic effect of antioxidants in vivo is disappointing due probably to the fact that once liver fibrogenesis is established it is too advanced to be reversed by anti-oxidation mechanism. We consider antioxidant may only act on the early phase of fibrogenesis. Thus, we had previously established an early liver fibrosis animal model using an inducible expression vector (pPK9a), which contains TGF-ß gene and was hydro-dynamically transferred into mice to induce a transient liver fibrosis. TGF-ß1 has been well documented to up-regulate the expression of α2(1) collagen (Col 1A2) gene in the liver via the reactive oxygen species (ROS); the process triggers inflammation, leading to hepatic stellate cells (HSC) activation and liver fibrogenesis. Using our animal model and ROS, cyclooxygenase-2 (Cox-2) and Col 1A2 promoter assays as screening targets, we report here that a maleic acid derivative isolated from the Antrodia camphorata mycelium strongly decreases ROS production, promoter activity of Cox-2 and Col 1A2, intracellular calcium, expression of alpha-smooth muscle actin (α-SMA), Smad4-p-Smad2/3 co-localization in cell nucleus and the DNA binding activity of Sp1. Our results suggest that the maleic acid derivative prevents liver fibrosis at an early phase both in vitro and in vivo through the inhibition of ROS, inflammation and the activation of HSC.
[Mh] Termos MeSH primário: Antioxidantes/farmacologia
Células Estreladas do Fígado/metabolismo
Cirrose Hepática/etiologia
Maleatos/farmacologia
Espécies Reativas de Oxigênio/metabolismo
Fator de Crescimento Transformador beta/fisiologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Transformada
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Maleates); 0 (Reactive Oxygen Species); 0 (Transforming Growth Factor beta); 91XW058U2C (maleic acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0174008


  8 / 3187 MEDLINE  
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[PMID]:28331124
[Au] Autor:Nakazawa A; Tang N; Inoue Y; Kamichatani W; Katoh T; Saito M; Obara K; Toriba A; Hayakawa K
[Ad] Endereço:Institute of Medical, Pharmaceutical and Health Sciences, Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
[Ti] Título:Evaluation of Adsorption Characteristics of a Fibrous Adsorbent Containing Zwitter-Ionic Functional Group, Targeting Organic Acids.
[So] Source:J UOEH;39(1):69-74, 2017.
[Is] ISSN:0387-821X
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:Diallylamine-maleic acid copolymer (DAM)-nonwoven fabric (DAM-f), a fibrous adsorbent, contains DAM with zwitter-ionic functional groups and forms a hydration layer on the surface. The aim of this report was to evaluate the adsorption selectivity of DAM-f to semi-volatile organic acid (C1-C5). In the aqueous phase, formic acid dissolved in the hydration layer bound to the imino group of DAM-f due to anion exchange interaction. In the gas phase, the adsorption amounts of organic acids increased with the exposure time. Moreover, the adsorption rate constants correlated with the air/water partition coefficients (log K ) for formic acid, propionic acid, butyric acid, valeric acid and isovaleric acid, except for acetic acid. These results indicate that DAM-f is highly selective to hydrophilic compounds which easily move from the air to the hydration layer of DAM-f.
[Mh] Termos MeSH primário: Ácido Acético
Ácido Butírico
Ácidos Pentanoicos
Propionatos
[Mh] Termos MeSH secundário: Adsorção
Ar
Alilamina/química
Ânions
Formiatos
Gases
Interações Hidrofóbicas e Hidrofílicas
Troca Iônica
Maleatos/química
Polímeros/química
Água
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anions); 0 (Formates); 0 (Gases); 0 (Maleates); 0 (Pentanoic Acids); 0 (Polymers); 0 (Propionates); 059QF0KO0R (Water); 0YIW783RG1 (formic acid); 107-92-6 (Butyric Acid); 1BR7X184L5 (isovaleric acid); 48G762T011 (Allylamine); 91XW058U2C (maleic acid); GZK92PJM7B (n-pentanoic acid); JHU490RVYR (propionic acid); Q40Q9N063P (Acetic Acid)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171015
[Lr] Data última revisão:
171015
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170324
[St] Status:MEDLINE
[do] DOI:10.7888/juoeh.39.69


  9 / 3187 MEDLINE  
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[PMID]:28326323
[Au] Autor:Nogueira A; Peixoto F; Oliveira MM; Pires CA; Colaço B; Oliveira PA; Pires MJ
[Ad] Endereço:Department of Veterinary Sciences, School of Agrarian and Veterinary Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal; Department of Therapeutic and Diagnostic Technologies, Polytechnic Institute of Bragança (IPB), Bragança, Portugal.
[Ti] Título:The Effects of Long-Term Chaetomellic Acid A Administration on Renal Function and Oxidative Stress in a Rat Model of Renal Mass Reduction.
[So] Source:Biomed Res Int;2017:5125980, 2017.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in a model of renal mass reduction. . Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment ( = 14); RMR + CAA: RMR rats treated with CAA ( = 13); SO: SO rats without treatment ( = 13); and SO + CAA: SO rats treated with CAA ( = 13). CAA was intraperitoneally administered in a dose of 0.23 g/Kg three times a week for six months. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity ( < 0.05) and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAA administration significantly increased catalase and GR activity ( < 0.05) and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio. No significant differences were found between the RMR groups in any of the parameters of renal function. However, CAA administration slightly improves some parameters of renal function. These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress.
[Mh] Termos MeSH primário: Nefropatias/tratamento farmacológico
Rim/efeitos dos fármacos
Maleatos/administração & dosagem
Estresse Oxidativo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Catalase/metabolismo
Glutationa/metabolismo
Seres Humanos
Rim/fisiopatologia
Rim/cirurgia
Nefropatias/patologia
Nefropatias/cirurgia
Masculino
Nefrectomia/efeitos adversos
Ratos
Superóxido Dismutase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Maleates); 148796-51-4 (chaetomellic acid A); EC 1.11.1.6 (Catalase); EC 1.15.1.1 (Superoxide Dismutase); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170418
[Lr] Data última revisão:
170418
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1155/2017/5125980


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[PMID]:28286081
[Au] Autor:Iglesias T; Dusinska M; El Yamani N; Irache JM; Azqueta A; López de Cerain A
[Ad] Endereço:Department of Pharmacology and Toxicology, Faculty of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain.
[Ti] Título:In vitro evaluation of the genotoxicity of poly(anhydride) nanoparticles designed for oral drug delivery.
[So] Source:Int J Pharm;523(1):418-426, 2017 May 15.
[Is] ISSN:1873-3476
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In the last years, the development of nanomaterials has significantly increased due to the immense variety of potential applications in technological sectors, such as medicine, pharmacy and food safety. Focusing on the nanodevices for oral drug delivery, poly(anhydride) nanoparticles have received extensive attention due to their unique properties, such as their capability to develop intense adhesive interactions within the gut mucosa, their modifiable surface and their biodegradable and easy-to-produce profile. However, current knowledge of the possible adverse health effects as well as, toxicological information, is still exceedingly limited. Thus, we investigated the capacity of two poly(anhydride) nanoparticles, Gantrez AN 119-NP (GN-NP) and Gantrez AN 119 covered with mannosamine (GN-MA-NP), and their main bulk material (Gantrez AN 119-Polymer), to induce DNA damage and thymidine kinase (TK ) mutations in L5178Y TK mouse lymphoma cells after 24h of exposure. The results showed that GN-NP, GN-MA-NP and their polymer did not induce DNA strand breaks or oxidative damage at concentrations ranging from 7.4 to 600µg/mL. Besides, the mutagenic potential of these nanoparticles and their polymer revealed no significant or biologically relevant gene mutation induction at concentrations up to 600µg/mL under our experimental settings. Considering the non-genotoxic effects of GN-NP and GN-MA-NP, as well as their exceptional properties, these nanoparticles are promising nanocarriers for oral medical administrations.
[Mh] Termos MeSH primário: Portadores de Fármacos/toxicidade
Maleatos/toxicidade
Nanopartículas/toxicidade
Polivinil/toxicidade
[Mh] Termos MeSH secundário: Administração Oral
Animais
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Dano ao DNA
Camundongos
Testes de Mutagenicidade
Mutação
Timidina Quinase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Carriers); 0 (Maleates); 0 (Polyvinyls); 0 (polyvinylmethoxyethylene-maleic anhydride copolymer); EC 2.7.1.21 (Thymidine Kinase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170314
[St] Status:MEDLINE



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