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1.
J Anim Sci ; 97(9): 3626-3635, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31505650

RESUMO

Arginine (Arg) is an important amino acid of pig fetal development; however, whether Arg improves postnatal performance is ill-defined. Therefore, the influence of Arg supplementation at different gestational stages on offspring performance was evaluated in a commercial swine herd. Sows (n = 548) were allocated into 4, diet by stage of gestation treatments: Control (n = 143; 0% suppl. Arg), or dietary treatments supplemented with 1% L-Arg (free-base; Ajinomoto Animal Nutrition North America, Inc., Chicago, IL): from 15 to 45 d of gestation (n = 138; Early-Arg); 15 d of gestation to farrowing (n = 139; Full-Arg); and from day 85 of gestation to farrowing (n = 128; Late-Arg). All offspring were individually identified and weighed at birth; at weaning, a subset was selected for evaluation of carcass performance at market. All data were analyzed using birth weight (BiWt) and age as covariates. Wean weights (WW) and prewean (PW) ADG tended to increase (P = 0.06) in progeny from sows supplemented with Arg, as compared to progeny from Control sows. Preplanned contrast comparisons revealed an increased (P = 0.03) BiWt for pigs from sows receiving 1% L-Arg prior to day 45 of gestation (Early-Arg and Full-Arg; 1.38 kg/pig), as compared to pigs from sows not supplemented prior to day 45 of gestation (Control and Late-Arg; 1.34 kg/pig). No difference in BiWt was observed (1.36 kg/pig; P = 0.68) for Arg supplementation after day 85 of gestation (Full-Arg and Late-Arg), as compared to those not receiving Arg supplementation after day 85 (Control and Early-Arg); although WW and PW ADG were greater (P = 0.02), respectively. A 3.6% decrease (P = 0.05) in peak lean accretion ADG occurred when dams received 1% L-Arg prior to day 45 of gestation (Early-Arg and Full-Arg), however, no other significant differences were detected in finishing growth parameters or carcass characteristics (P ≥ 0.1). Pig mortality rates tended (P = 0.07) to decrease in progeny of dams supplemented Arg after day 85 (3.6%) compared to dams not provided additional Arg during late gestation (4.9%). Collectively, these data suggest that Arg provided during late gestation may improve WW and PW ADG, however, finishing performance was not affected. While Arg supplementation provided some moderate production benefits, further investigation is warranted to comprehensively understand the gestational timing and biological role of Arg supplementation during fetal and postnatal development in commercial production systems.


Assuntos
Arginina/farmacologia , Suplementos Nutricionais , Suínos/fisiologia , Animais , Peso ao Nascer/efeitos dos fármacos , Dieta/veterinária , Feminino , Parto/efeitos dos fármacos , Gravidez , Desmame
2.
Int J Food Microbiol ; 306: 108272, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31376617

RESUMO

In this study, zein coatings containing Lauroyl-l-arginine ethyl ester monohydrochloride (LAE) were developed to be applied on polypropylene films and manufacture an active food packaging. The concentration of LAE and the addition of a suitable plasticizer (glycerol or oleic acid (OA)) were the main variables considered. Active plasticized zein films, with glycerol or oleic acid were characterized in terms of release kinetics, mechanical, barrier, optical, and antimicrobial properties. Results showed that active agent concentration, (5 and 10%), had no-significant effect on mechanical and WVP properties of the plasticized films. Films plasticized with OA presented greater water resistance, UV-light opacity, and water barrier properties than glycerol-plasticized films. On the contrary, the latter had better antimicrobial properties. The analysis of LAE release kinetics from films to different food simulants revealed different behaviours, depending on both film formulation and food simulant. Despite the lower water resistance of coatings containing glycerol, bags based on polypropylene/glycerol plasticized zein containing 10% of LAE presented a great antimicrobial activity in tests with chicken soup (real food system) contaminated with pathogen bacteria, concretely, the films showed 3.21 Log reduction against Listeria monocytogenes and 3.07 log reductions against Escherichia coli. These results suggest a promising strategy on the use of LAE-containing zein in active food packaging to control foodborne pathogens.


Assuntos
Antibacterianos/farmacologia , Arginina/análogos & derivados , Escherichia coli/crescimento & desenvolvimento , Embalagem de Alimentos/métodos , Listeria monocytogenes/crescimento & desenvolvimento , Zeína/farmacologia , Animais , Arginina/farmacologia , Galinhas , Escherichia coli/efeitos dos fármacos , Listeria monocytogenes/efeitos dos fármacos , Água
3.
J Chem Theory Comput ; 15(10): 5461-5473, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31436990

RESUMO

Predicting the effect of single-point mutations on protein stability or protein-ligand binding is a major challenge in computational biology. Free energy calculations constitute the most rigorous approach to this problem, though the estimation of converged values for amino acid mutations remains challenging. To overcome this limitation, we developed tailored protocols to calculate free energy shifts associated with single-point mutations. We herein describe the QresFEP protocol, which includes an extension of our recent protocols to cover all amino acids mutations, based on the latest versions of the OPLS-AA force field. QresFEP is implemented in an application programming interface framework and the graphic interface QGui, for the molecular dynamics software Q. The complete protocol is benchmarked in several model systems, optimizing a number of sampling parameters and the implementation of Zwanzig's exponential formula and Bennet's acceptance ratio methods. QresFEP shows an excellent performance on estimating the hydration free energies of amino acid side-chain mimics, including their charged analogues. We also examined its performance on a protein-ligand binding problem of pharmaceutical relevance, the antagonism of neuropeptide Y1 G protein-coupled receptor. Here, the calculations show very good agreement with the experimental effect of 16 mutations on the binding of antagonists BIBP3226, in line with our recent applications in this field. Finally, the characterization of 43 mutations of T4-lysozyme reveals the capacity of our protocol to assess variations of the thermal stability of proteins, achieving a similar performance to alternative free energy perturbation (FEP) approaches. In summary, QresFEP is a robust, versatile, and user-friendly computational FEP protocol to examine biochemical effects of single-point mutations with high accuracy.


Assuntos
Arginina/análogos & derivados , Automação , Simulação de Dinâmica Molecular , Proteínas Mutantes/química , Receptores de Neuropeptídeo Y/química , Software , Termodinâmica , Arginina/química , Arginina/farmacologia , Ligantes , Proteínas Mutantes/antagonistas & inibidores , Estabilidade Proteica , Receptores de Neuropeptídeo Y/antagonistas & inibidores
4.
J Anim Sci ; 97(9): 3617-3625, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31298271

RESUMO

Supplemental arginine (Arg) during gestation purportedly benefits fetal development. However, the benefits of a gestational Arg dietary strategy in commercial production are unclear. Therefore, the objectives of this study examined Arg supplementation during different gestational stages and the effects on gilt reproductive performance. Pubertal gilts (n = 548) were allocated into 4 treatment groups: Control (n = 143; 0% supplemental Arg) or 1 of 3 supplemental Arg (1% as fed) treatments: from 15 to 45 d of gestation (n = 138; Early-Arg); from 15 d of gestation until farrowing (n = 139; Full-Arg); or from 85 d of gestation until farrowing (n = 128; Late-Arg). At farrowing, the number of total born (TB), born alive (BA), stillborn piglets (SB), mummified fetuses (MM), and individual piglet birth weights (BiWt) were recorded. The wean-to-estrus interval (WEI) and subsequent sow reproductive performance (to third parity) were also monitored. No significant effect of supplemental Arg during any part of P0 gestation was observed for TB, BA, SB, or MM (P ≥ 0.29). Offspring BiWt and variation among individual piglet birth weights did not differ (P = 0.42 and 0.89, respectively) among treatment groups. Following weaning, the WEI was similar among treatments (average of 8.0 ± 0.8 d; P = 0.88). Litter performance over 3 parities revealed a decrease (P = 0.02) in BA for Early-Arg fed gilts compared with all other treatments, whereas TB and WEI were similar among treatments over 3 parities (P > 0.05). There was an increased proportion of sows with average size litters (12 to 16 TB) from the Full-Arg treatment sows (76.8% ± 3.7%) when compared with Control (58.7% ± 4.2%; P = 0.01); however, the proportion of sows with high (>16 TB) and low (<12 TB) litters was not different among treatments (P = 0.20). These results suggest that gestational Arg supplementation had a minimal impact on reproductive performance in first parity sows. These data underscore the complexity of AA supplementation and the need for continued research into understanding how and when utilizing a gestational dietary Arg strategy can optimize fetal development and sow performance.


Assuntos
Arginina/farmacologia , Suplementos Nutricionais , Reprodução , Suínos/fisiologia , Animais , Peso ao Nascer/efeitos dos fármacos , Dieta/veterinária , Estro/efeitos dos fármacos , Feminino , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Paridade/efeitos dos fármacos , Parto/efeitos dos fármacos , Gravidez , Desmame
5.
Life Sci ; 233: 116684, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31351083

RESUMO

Traumatic brain injury (TBI) is a devastating condition that often triggers a sequel of neurological disorders that can last throughout lifespan. From a metabolic viewpoint, the compromising of the energy metabolism of the brain has produced evidence linking the severity of brain injury to the extent of disturbances in the cerebral metabolism. The cerebral metabolic crisis, however, displays that regional heterogeneity varies temporally post-injury. It is important to note that energy generation and mitochondrial function are closely related and interconnected with delayed secondary manifestations of brain injury, including early neuromotor dysfunction, cognitive impairment, and post-traumatic epilepsy (PTE). Given the extent of post-traumatic changes in neuronal function and the possibility of amplifying secondary cascades, different therapies designed to minimize damage and retain/restore cellular function after TBI are currently being studied. One of the possible strategies may be the inclusion of ergogenic compounds, which is a class of supplements that typically includes ingredients used by athletes to enhance their performance. The combination of these compounds offers specific physiological advantages, which include enhanced energy availability/metabolism and improved buffering capacity. However, the literature on their effects in certain biological systems and neurological diseases, such as TBI, has yet to be determined. Thus, the present review aims to discuss the role of ergogenic compounds popularly used in secondary damage induced by this neurological injury. In this narrative review, we also discuss how the results from animal studies can be applied to TBI clinical settings.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Disfunção Cognitiva/tratamento farmacológico , Epilepsia Pós-Traumática/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Doenças Neuromusculares/tratamento farmacológico , Animais , Arginina/farmacologia , Cafeína/farmacologia , Carnitina/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Creatina/farmacologia , Metabolismo Energético , Epilepsia Pós-Traumática/etiologia , Epilepsia Pós-Traumática/fisiopatologia , Glutamina/farmacologia , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Doenças Neuromusculares/etiologia , Doenças Neuromusculares/fisiopatologia , Taurina/farmacologia
6.
Life Sci ; 232: 116604, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31260684

RESUMO

Chronic kidney disease (CKD) patients present L-arginine (L-arg) deficiency and L-arg supplementation has been used as a treatment. In addition, sarcopenia is another common problem in CKD population, resistance training (RT) is one of the conservative strategies developed to prevent CKD progression, and however there are no evidences of a combination of these two strategies to treat CKD outcomes. The aim of this study was to evaluate the effects of oral L-arg supplementation combined with RT in an experimental model of CKD. Twenty-five Munich-Wistar male rats, 8-week-old were divided in 5 groups: Sham (sedentary control), Nx (CKD sedentary), Nx L-arg (CKD sedentary supplemented with 2% of L-arg), Nx RT (CKD exercised) Nx RT + L-arg (CKD exercised and supplemented with 2% of L-arg). CKD model was obtained by a subtotal 5/6 nephrectomy. RT was performed on a ladder climbing, three weekly sessions on non-consecutive days, with an intensity of 70% maximum carrying capacity. They were submitted to RT and/or L-arg supplementation for 10 weeks. There was a significant improvement in muscle strength, renal function, anti-inflammatory cytokines, arginase metabolism and renal fibrosis after RT. However, the combination of RT and L-arg impaired all the improvements promoted by RT alone. The L-arg supplementation alone did not impair renal fibrosis and renal function. In conclusion, RT improved inflammatory balance, muscle strength, renal function and consequently decreased renal fibrosis. Nevertheless, the association with L-arg supplementation prevented all these effects promoted by RT.


Assuntos
Arginina/farmacologia , Condicionamento Físico Animal/fisiologia , Insuficiência Renal Crônica/dietoterapia , Animais , Arginina/metabolismo , Citocinas/metabolismo , Suplementos Nutricionais , Progressão da Doença , Fibrose/metabolismo , Rim/metabolismo , Masculino , Força Muscular/efeitos dos fármacos , Músculo Esquelético/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Condicionamento Físico Animal/métodos , Ratos , Ratos Wistar , Insuficiência Renal Crônica/metabolismo , Treinamento de Resistência/métodos
7.
BMC Vet Res ; 15(1): 199, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196135

RESUMO

BACKGROUND: The purpose of the present study was to assess if the exposure to glutamine (Gln), arginine (Arg) or their combination from pregnancy, through the maternal diet, to a post weaning supplemented diet, can stimulate litter performance, gut development and immune function. To this end does and their litters were fed the same basal diet no supplemented (control C), or supplemented with 0.4% Gln, 0.4% Arg, or 0.4 Gln + 0.4 Arg. Rabbits were weaned at 25 d of age and fed the same experimental diet as their mothers for 10 additional days (35 d of age). Bacterial translocation to mesenteric lymph nodes (MLN) at 6 d of age and intestinal histology, enzymatic activity, phenotypical and functional analysis of intraepithelial lymphocytes (IEL) from the appendix were determined at 6, 25 and 35 d of age. RESULTS: No significant differences on animal performance or mortality rates were observed among dietary treatments. However, kits from rabbit does supplemented with Gln tended (P ≤ 0.10) to reduce the translocation of total number of both aerobic and facultative anaerobic bacteria to the MLN. Also, rabbits fed the Gln supplemented diets maintained intestinal villous height at weaning compared to the non-supplemented diets (P < 0.05). The proportions of CD45+CD4+ and CD45+CD8+ IEL in the appendix were not affected by dietary means. However, in rabbits IEL at weaning dietary Gln significantly upregulated IL-2 and downregulated IL-6 expression. CONCLUSIONS: Despite a lack of effect on performance and mortality the inclusion of 0.4% Gln has a positive effect by maintaining intestinal villous height and modulating the cytokine profile at weaning. The supplementation with Arg or Arg + Gln at the selected doses in this study did not exert positive effects on rabbit intestinal health.


Assuntos
Arginina/farmacologia , Dieta/veterinária , Glutamina/farmacologia , Intestinos/efeitos dos fármacos , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Arginina/administração & dosagem , Bactérias , Feminino , Glutamina/administração & dosagem , Intestinos/anatomia & histologia , Intestinos/enzimologia , Intestinos/microbiologia , Linfócitos Intraepiteliais/fisiologia , Linfonodos/microbiologia , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Coelhos , Desmame
8.
Int J Nanomedicine ; 14: 3503-3516, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190807

RESUMO

Purpose: The NLRP3 inflammasome activation has been proposed as a common mechanism for some adjuvants to boost the immune system, and cationic liposomes were reported to potentially activate the NLRP3 inflammasome. Herein, we questioned whether the NLRP3 inflammasome-activating cationic liposomes could promote antigen presentation and be applied as an immune adjuvant. In addition, we aimed to investigate the structure effect of lipid on triggering these immune responses. Materials and methods: A series of structurally similar lipids, consisting of arginine (Arg) head group and varied lengths of alkyl chains or spacers in between were used to prepare cationic liposomes. Lipopolysaccharide-primed human or murine macrophages or phorbol 12-myristate 13-acetate-primed THP-1 cells were treated with these liposomes, and interleukin (IL)-1ß secretion was measured to quantify the NLRP3 inflammasome activation. Lysosome rupture was examined in THP-1 cells by the fluorescence loss of acridine orange, a lysosome dye. Further, chicken ovalbumin (OVA) was loaded on the liposome surface and applied to murine bone marrow-derived dendritic cells (BMDCs), which activate OT-I and OT-II lymphocytes upon major histocompatibility complex (MHC) class I- and class II-mediated antigen presentation, respectively. OT-I and OT-II cell division and IL-2 secretion were measured to evaluate the antigen presentation efficiency. The expressions of MHC molecules and co-stimulatory molecules ie, CD80, CD86, and CD40 on BMDCs were investigated by flow cytometry. Results: All the liposomes showed size distributions of 80-200 nm and zeta potentials of around 50 mV. A3C14 liposomes, consisting of Arg-C3-Glu2C14 lipids induced the most potent lysosome rupture and NLRP3 inflammasome activation. OVA-A3C14 also exhibited the most potent MHC class I- and class II-mediated antigen presentation in BMDCs without interfering MHC and co-stimulatory molecules. Conclusion: The hydrophobic moieties of arginine-based liposomes are crucial in stimulating innate immune cells. A3C14 liposomes were non-immunogenic but strongly activated innate immune cells and promoted antigen presentation, and therefore can be applied as immune adjuvants.


Assuntos
Apresentação do Antígeno/efeitos dos fármacos , Arginina/farmacologia , Células Dendríticas/imunologia , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Cátions , Células Dendríticas/efeitos dos fármacos , Feminino , Antígenos de Histocompatibilidade/metabolismo , Humanos , Lipídeos/química , Lipopolissacarídeos/farmacologia , Lipossomos , Lisossomos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL
9.
Am J Dent ; 32(2): 81-88, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31094142

RESUMO

PURPOSE: To evaluate the effect on dentin of chondroitin sulfate and L-arginine on dentin tubule occlusion. METHODS: The dentin samples were activated by submersion in an aqueous ( aq. ) solution of chondroitin sulfate ( ChS) or L-arginine prior to application of a commercial or custom-made toothpaste. After rinsing with water and ultrasonication, adhesion to dentin and occlusion of dentin tubules were evaluated by scanning electron microscopy and the elemental composition of the deposits was evaluated by energy-dispersive x-ray spectroscopy. RESULTS: Rinsing a dentin sample with a solution of ChS resulted in an increase in the adherence of dentifrices containing either titanium dioxide (TiO2 ) or calcium-based nanoparticles [ hydroxyapatite ( HA\ or calcium carbonate( to the dentin surface. ChS does not appear to enhance the adherence of dentifrices lacking TiO2. Pretreatment by L-arginine improved adherence of calcium carbonate nanoparticles, but less efficiently than ChS. Addition of nanoparticles of hydroxyapatite or calcium citrate to dentifrices improved their adherence to dentin without any pre-treatment. CLINICAL SIGNIFICANCE: The significant increase in adherence to the dentin surface of dentifrices of either TiO2 or calcium-supplying nanoparticles to the dentin surface following pre-treatment with ChS or L-arginine opens the door to the development of two-step dental treatments, which accomplish dentin tubule occlusion and help to deliver active dentifrice components to the dentin surface. The ability of the aqueous pastes of nanoparticles of hydroxyapatite or calcium citrate to occlude dentin tubules enables the formulation of desensitizing dentifrices, which also supply the mineral and organic nutrients to the tooth surface.


Assuntos
Dentifrícios , Dessensibilizantes Dentinários , Sensibilidade da Dentina , Cremes Dentais , Arginina/farmacologia , Carbonato de Cálcio/farmacologia , Sulfatos de Condroitina/farmacologia , Dentifrícios/química , Dentifrícios/farmacologia , Dentina , Fluoretos , Humanos , Microscopia Eletrônica de Varredura , Cremes Dentais/química , Cremes Dentais/farmacologia
10.
RNA Biol ; 16(7): 972-987, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31043113

RESUMO

CsrA is a widely conserved, abundant small RNA binding protein that has been found in E. coli and other Gram-negative bacteria where it is involved in the regulation of carbon metabolism, biofilm formation and virulence. CsrA binds to single-stranded GGA motifs around the SD sequence of target mRNAs where it inhibits or activates translation or influences RNA processing. Small RNAs like CsrB or CsrC containing 13-22 GGA motifs can sequester CsrA, thereby abrogating the effect of CsrA on its target mRNAs. In B. subtilis, CsrA has so far only been found to regulate one target, hag mRNA and to be sequestered by a protein (FliW) and not by an sRNA. Here, we employ a combination of in vitro and in vivo methods to investigate the effect of CsrA on the small regulatory RNA SR1 from B. subtilis, its primary target ahrC mRNA and its downstream targets, the rocABC and rocDEF operons. We demonstrate that CsrA can promote the base-pairing interactions between SR1 and ahrC mRNA, a function that has so far only been found for Hfq or ProQ. Abbreviations: aa, amino acid; bp, basepair; nt, nucleotide; PAA, polyacrylamide; SD, Shine Dalgarno.


Assuntos
Bacillus subtilis/metabolismo , Proteínas de Bactérias/metabolismo , RNA Bacteriano/metabolismo , Arginina/farmacologia , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/genética , Bacillus subtilis/crescimento & desenvolvimento , Pareamento de Bases/genética , Sequência de Bases , Carbono/farmacologia , Regulação Bacteriana da Expressão Gênica , Mutação/genética , Conformação de Ácido Nucleico , Regiões Promotoras Genéticas/genética , Ligação Proteica , Biossíntese de Proteínas , Estabilidade de RNA/genética , RNA Bacteriano/química , RNA Bacteriano/genética , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ribonucleases/metabolismo , Transcrição Genética
11.
Biotechnol Appl Biochem ; 66(5): 772-780, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31119802

RESUMO

Nowadays, putting forward an accurate cancer therapy method with minimal side effects is an important topic of research. Nanostructures, for their ability in controlled and targeted drug release on specific cells, are critical materials in this field. In this study, a pH-sensitive graphene oxide-l-arginine nanogel was synthesized to carry and release 5-fluorouracil. Optimized conditions using statistical analysis, based on the maximum relative viscosity of nanogel, were evaluated: 5.489 for the concentration of l-arginine and 2.404 for pH. The prepared nanogels were characterized using scanning electron microscope and transmission electron microscope images and Fourier-transform infrared spectroscopic analysis. Cytotoxicity was assessed using the sulforhodamine B (SRB) assay on MCF-7 breast cancer cells. The fluorouracil release was measured by the dialysis bag method, UV spectrophotometry, and fluorouracil calibration diagram. Results proved the successful controlled release of fluorouracil at pH 5.4 and the beneficial role of graphene-oxide- l-arginine- fluorouracil nanogel in eliminating cancer cells.


Assuntos
Arginina/farmacologia , Fluoruracila/farmacologia , Grafite/farmacologia , Nanopartículas/química , Polietilenoglicóis/farmacologia , Polietilenoimina/farmacologia , Arginina/química , Sobrevivência Celular/efeitos dos fármacos , Fluoruracila/química , Grafite/química , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoimina/química , Propriedades de Superfície
12.
Nutrients ; 11(4)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999554

RESUMO

Although several kinds of amino acids (AAs) are known to affect physiological actions during exercise, little is known about the combined effects of a mixture of several AAs on fatigue during exercise. The aim of the present study was to investigate the effect of an AA mixture supplement containing arginine, valine, and serine on exercise-induced fatigue in healthy volunteers. These AAs were selected because they were expected to reduce fatigue during exercise by acting the positive effects synergistically. A randomized, double-blinded, placebo-controlled crossover trial was conducted. Thirty-nine males ingested an AA mixture containing 3600 mg of arginine, 2200 mg of valine, and 200 mg of serine or a placebo each day for 14 days. On the 14th day, the participants completed an exercise trial on a cycle ergometer at 50% of VO2max for 120 min. After the two-week washout period, the participants repeated the same trial with the other test sample. The participant's feeling of fatigue based on a visual analog scale (VAS) and a rating of perceived exertion (RPE), as well as blood and physical parameters were evaluated. The feeling of fatigue based on VAS and RPE were significantly improved in AA compared to those in placebo. In the blood analysis, the increase in serum total ketone bodies during exercise and plasma tryptophan/branched-chain amino acids were significantly lower in AA than those in placebo. The present study demonstrated that supplementation with an AA mixture containing arginine, valine, and serine reduced the feeling of fatigue during exercise. The AA mixture also changed several blood parameters, which may contribute to the anti-fatigue effect.


Assuntos
Arginina/administração & dosagem , Exercício/fisiologia , Fadiga/prevenção & controle , Serina/administração & dosagem , Valina/administração & dosagem , Adulto , Arginina/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Sinergismo Farmacológico , Fadiga/etiologia , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Serina/farmacologia , Valina/farmacologia
13.
Int J Mol Sci ; 20(8)2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027156

RESUMO

We investigated whether the substrate for nitric oxide (NO) production, extracellular l-arginine, contributes to relaxations induced by activating small (SKCa) conductance Ca2+-activated potassium channels. In endothelial cells, acetylcholine increased 3H-l-arginine uptake, while blocking the SKCa and the intermediate (IKCa) conductance Ca2+-activated potassium channels reduced l-arginine uptake. A blocker of the y+ transporter system, l-lysine also blocked 3H-l-arginine uptake. Immunostaining showed co-localization of endothelial NO synthase (eNOS), SKCa3, and the cationic amino acid transporter (CAT-1) protein of the y+ transporter system in the endothelium. An opener of SKCa channels, cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (CyPPA) induced large currents in endothelial cells, and concentration-dependently relaxed porcine retinal arterioles. In the presence of l-arginine, concentration-response curves for CyPPA were leftward shifted, an effect unaltered in the presence of low sodium, but blocked by l-lysine in the retinal arterioles. Our findings suggest that SKCa channel activity regulates l-arginine uptake through the y+ transporter system, and we propose that in vasculature affected by endothelial dysfunction, l-arginine administration requires the targeting of additional mechanisms such as SKCa channels to restore endothelium-dependent vasodilatation.


Assuntos
Arginina/farmacologia , Arteríolas/fisiologia , Espaço Extracelular/química , Ativação do Canal Iônico/efeitos dos fármacos , Vasos Retinianos/fisiologia , Vasodilatação/efeitos dos fármacos , Animais , Arteríolas/efeitos dos fármacos , Transportador 1 de Aminoácidos Catiônicos/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Óxido Nítrico Sintase Tipo III/metabolismo , Pirazóis/farmacologia , Pirimidinas/farmacologia , Ratos , Vasos Retinianos/efeitos dos fármacos , Canais de Potássio Ativados por Cálcio de Condutância Baixa , Suínos
14.
Int J Mol Sci ; 20(7)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30979040

RESUMO

This study aimed to explore the effect of L-arginine on lipopolysaccharide (LPS)-induced inflammatory response and oxidative stress in IPEC-2 cells. We found that the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), cluster of differentiation 14 (CD14), nuclear factor-kappaBp65 (NF-κBp65), chemokine-8 (IL-8), tumor necrosis factor (TNF-α) and chemokine-6 (IL-6) mRNA were significantly increased by LPS. Exposure to LPS induced oxidative stress as reactive oxygen species (ROS) and malonaldehyde (MDA) production were increased while glutathione peroxidase (GSH-Px) were decreased in LPS-treated cells compared to those in the control. LPS administration also effectively induced cell growth inhibition through induction of G0/G1 cell cycle arrest. However, compared with the LPS group, cells co-treatment with L-arginine effectively increased cell viability and promoted the cell cycle into the S phase; L-arginine exhibited an anti-inflammatory effect in alleviating inflammation induced by LPS by reducing the abundance of TLR4, MyD88, CD14, NF-κBp65, and IL-8 transcripts. Cells treated with LPS+L-arginine significantly enhanced the content of GSH-Px, while they decreased the production of ROS and MDA compared with the LPS group. Furthermore, L-arginine increased the activity of arginase-1 (Arg-1), while Arg-1 inhibitor abolished the protection of arginine against LPS-induced inflammation and oxidative stress. Taken together, these results suggested that L-arginine exerted its anti-inflammatory and antioxidant effects to protect IPEC-J2 cells from inflammatory response and oxidative stress challenged by LPS at least partly via the Arg-1 signaling pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Arginase/imunologia , Arginina/farmacologia , Inflamação/tratamento farmacológico , Lipopolissacarídeos/imunologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inflamação/imunologia , Transdução de Sinais/efeitos dos fármacos , Suínos
15.
Biomed Pharmacother ; 113: 108768, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30889486

RESUMO

Pulmonary fibrosis (PF) progression may be involved with arginine (Arg) metabolism and immune balance. The present study aimed to explore the effects of L-Arginine (L-Arg) and L-Norvaline (L-Nor) on bleomycin (BLM)-induced PF in mice, meanwhile, and observe dynamic changes of Arg metabolism, immune balance and crosstalk between them in PF progression. Followed intratracheal instillation of BLM or saline, Kunming mice were treated orally with saline, L-Arg, L-Nor and L-Arg + L-Nor three times a day. And the mice were sacrificed on Day 3, 14 and 28 after treatment. Changes of body weight, lung index, lung hydroxyproline and histopathology were analyzed to evaluate the PF degree. Peripheral blood Arg, Citrulline (Cit), Ornithine (Orn) and Proline (Pro), lung NO, NOS and arginase were analyzed to evaluate the Arg metabolism. Peripheral blood Tregs, Th17 and γδT cells were analyzed to evaluate the immune balance. Our data showed that combination of L-Arg and L-Nor dynamically reversed the weight loss, decreased lung index and hydroxyproline, and improved lung histopathological damages induced by BLM. The combination dynamically and significantly rectified Tregs, Th17, γδT and Tregs/Th17 abnormal changes. Meanwhile, these disorders of peripheral blood Arg, Cit, Orn, Pro, Orn/Cit and Pro/Orn, and lung NO, iNOS and TNOS were also improved accordingly. These results demonstrated that combination of L-Arg and L-Nor had inhibitory effects on BLM-induced PF progression, possibly due to their corrective action on immune imbalance, Arg metabolism disorder and crosstalk abnormality in the progression of PF.


Assuntos
Arginina/administração & dosagem , Pulmão/efeitos dos fármacos , Fibrose Pulmonar/prevenção & controle , Valina/análogos & derivados , Administração Oral , Animais , Arginina/farmacologia , Bleomicina/toxicidade , Modelos Animais de Doenças , Progressão da Doença , Quimioterapia Combinada , Linfócitos Intraepiteliais/imunologia , Pulmão/patologia , Masculino , Camundongos , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/patologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Valina/administração & dosagem , Valina/farmacologia
16.
J Anim Physiol Anim Nutr (Berl) ; 103(3): 791-800, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30815917

RESUMO

Forty-eight Duroc × Large White × Landrace pigs with an average initial body weight of 77.09 ± 1.37 kg were used to investigate the effects of combination of leucine (Leu) with arginine (Arg) or glutamic acid (Glu) on muscle growth, free amino acid profiles, expression levels of amino acid transporters and growth-related genes in skeletal muscle. The animals were randomly assigned to one of the four treatment groups (12 pigs/group, castrated male:female = 1:1). The pigs in the control group were fed a basal diet (13% Crude Protein), and those in the experimental groups were fed the basal diet supplemented with 1.00% Leu (L group), 1.00% Leu + 1.00% Arg (LA group) or 1.00% Leu + 1.00% Glu (LG group). The experiment lasted for 60 days. Results showed an increase (p < 0.05) in biceps femoris (BF) muscle weight in the L group and LG group relative to the basal diet group. In longissimus dorsi (LD) muscle, Lys, taurine and total essential amino acid concentration increased in the LG group relative to the basal diet group (p < 0.05). In LG group, Glu and carnosine concentrations increased (p < 0.05) in the BF muscle, when compared to the basal diet group. The Leu and Lys concentrations of BF muscle were lower in the LA group than that in the L group (p < 0.05). A positive association was found between BF muscle weight and Leu concentration (p < 0.05). The LG group presented higher (p < 0.05) mRNA levels of ASCT2, LAT1, PAT2, SANT2 and TAT1 in LD muscle than those in the basal diet group. The mRNA levels of PAT2 and MyoD in BF muscle were upregulated (p < 0.05) in the LG group, compared with those in the basal diet group. In conclusion, Leu alone or in combination with Glu is benefit for biceps femoris muscle growth in fattening pig.


Assuntos
Arginina/farmacologia , Ácido Glutâmico/farmacologia , Leucina/farmacologia , Músculo Esquelético/crescimento & desenvolvimento , Suínos/crescimento & desenvolvimento , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Arginina/administração & dosagem , Arginina/sangue , Dieta/veterinária , Suplementos Nutricionais , Quimioterapia Combinada , Regulação da Expressão Gênica/efeitos dos fármacos , Ácido Glutâmico/administração & dosagem , Ácido Glutâmico/sangue , Leucina/administração & dosagem , Leucina/sangue , Distribuição Aleatória , Regulação para Cima
17.
Eur J Appl Physiol ; 119(5): 1075-1084, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30847640

RESUMO

PURPOSE: Oral L-citrulline (Cit) increases plasma L-arginine (Arg) concentration and the production of nitric oxide (NO). NO dilates blood vessels and potentially improves sports performance. The combination of oral Arg and Cit (Arg + Cit) immediately and synergistically increases plasma Arg and nitrite/nitrate (NOx) concentrations more than either Cit or Arg alone. This prompted us to assess the effects of oral Arg + Cit on 10-min cycling performance in a double-blind, randomized, placebo-controlled crossover trial. METHODS: Twenty-four male soccer players ingested either Cit + Arg or placebo (both 1.2 g/day each) for 6 days. On day 7, they ingested Cit + Arg 1 h before performing a 10-min full-power pedaling test on a bicycle ergometer. Plasma NOx and amino acid levels were measured before and after the test, as well as the participants' subjective perception of physical exertion. RESULTS: Power output was significantly greater with Cit + Arg than in the placebo group (242 ± 24 vs. 231 ± 21 W; p < 0.05). Plasma concentrations of post-exercise NOx (p < 0.05), Cit (p < 0.01) and Arg (p < 0.01) were significantly higher in the Cit + Arg than in the placebo group, whereas exercise upregulated plasma NOx concentrations in both groups (p < 0.05). Cit + Arg also gave improved post-exercise subjective perception of "leg muscle soreness" and "ease of pedaling" (both p < 0.05). CONCLUSION: Seven days of oral Citrulline (1.2 g/d) and Arginine (1.2 g/d) ingestion improved 10-min cycling performance and the perception of physical exertion in male collegiate soccer players.


Assuntos
Arginina/farmacologia , Citrulina/farmacologia , Tolerância ao Exercício/efeitos dos fármacos , Administração Oral , Adolescente , Adulto , Arginina/administração & dosagem , Citrulina/administração & dosagem , Combinação de Medicamentos , Humanos , Masculino , Futebol/fisiologia
18.
Can J Physiol Pharmacol ; 97(5): 359-369, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30916578

RESUMO

Hepatic injury is one of the most common complications associated with cisplatin (CIS) use. Recently, liver protection lines are being discovered to stop the hepatic cell death due to inflammatory and apoptotic perturbations. l-arginine has protective effects in several models of liver injury. This study was designed to investigate the possible protective effect of l-arginine against CIS-induced acute hepatic injury in rats. Rats were divided into 4 groups: control, l-arginine, CIS, l-arginine + CIS. Liver function, oxidative stress, inflammatory cytokines, and apoptosis markers were assessed. l-arginine pretreatment protected the liver against CIS-induced toxicity as indicated by significantly alleviating the changes in liver function along with restoration of the antioxidant status. This finding was confirmed with the markedly improved pathological changes. l-arginine showed anti-inflammatory effect through the reduction of liver expression of iNOS, TNF-α, and NF-κß, which were ameliorated to significant levels. Furthermore, l-arginine administration downregulated the liver expression of the apoptotic marker, caspase-3. The results recommend l-arginine as a hepatoprotective agent against CIS toxicity. Mostly, this hepatoprotective effect of l-arginine involved anti-inflammatory and anti-apoptotic activities.


Assuntos
Apoptose/efeitos dos fármacos , Arginina/farmacologia , Cisplatino/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Alanina Transaminase/metabolismo , Animais , Aspartato Aminotransferases/metabolismo , Biomarcadores/metabolismo , Caspase 3/metabolismo , Citoproteção/efeitos dos fármacos , Inflamação/metabolismo , Fígado/patologia , Masculino , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Fator de Necrose Tumoral alfa/metabolismo
19.
Food Chem ; 284: 219-226, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-30744849

RESUMO

This study aimed to evaluate the effects of l-lysine (Lys)/l-arginine (Arg)/l-cysteine (Cys) on the color of cured sausage and the possible mechanism underlying these effects. The results indicated that the combined addition of Arg/Lys/Cys and NaNO2 effectively increased the a* values and nitroso pigment content but decreased the MetMb(Fe3+) content in cured sausage, compared with the individual addition of Arg/Lys/Cys and NaNO2. The cured sausage treated with combined Arg/Lys/Cys and NaNO2 contained significantly lower residual nitrite than those treated with only NaNO2. UV-vis spectroscopy and electron paramagnetic resonance spectroscopy revealed that pentacoordinate nitrosyl ferrohemochrome was the main pigment component in the cured sausage treated with NaNO2 or combined Arg/Lys/Cys and NaNO2 and higher content in the latter one. The results suggest that Arg/Lys/Cys hindered myoglobin oxidation and promoted pentacoordinate nitrosylmyoglobin formation, which could contribute to the improved color of cured sausage. The results are of interest in the meat industry.


Assuntos
Arginina/farmacologia , Cisteína/farmacologia , Lisina/farmacologia , Mioglobina/metabolismo , Carne Vermelha , Animais , Cor , Conservação de Alimentos/métodos , Óxido Nítrico , Oxirredução , Nitrito de Sódio
20.
Fish Physiol Biochem ; 45(2): 539-549, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30729411

RESUMO

Dietary arginine (Arg) could improve the intestinal structure and absorption of grass carp (Ctenopharyngodon idellus); however, the mechanism of Arg on intestinal morphology improvement was unclear. The present study aimed to explain the possible mechanism of the positive effect of Arg on intestinal epithelial cells of grass carp. An in vitro study was conducted through a primary culture model to assess the growth, cell viability, mRNA expressions of TOR signal pathway, and tight junction proteins of enterocytes after culture in the medium with 6 levels of Arg (0, 0.1, 0.2, 0.5, 1.0, and 2.0 mmol/L). The results showed that 0.5 mmol/L Arg improved the cell number and decreased the lactate dehydrogenase and creatine kinase activities in culture medium (P < 0.05). The alkaline phosphatase activity in cell lysis buffer was depressed by 1 and 2 mmol/L Arg (P < 0.05). The nitric oxide (NO) content showed an increasing trend with the Arg content (P < 0.05), whereas the NO synthase activity showed an opposite trend to NO. TOR expression was higher in 0.2 and 0.5 mmol/L groups, whereas S6K1 expression in 1.0 mmol/L and 2.0 mmol/L groups were lower (P < 0.05). The mRNA expressions of occludin, claudin 3, and claudin c in 0.5 mmol/L group were the highest, while ZO-1 and claudin b expressions were higher in 0.2 and 0.5 mmol/L groups (P < 0.05). This study indicated that Arg enhanced the growth and integrity of intestinal epithelial cells of grass carp through upregulation of mRNA expression of TOR signal pathway and tight junction proteins at an optimal Arg content of 0.2-0.5 mmol/L.


Assuntos
Arginina/farmacologia , Carpas/fisiologia , Enterócitos/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Proteínas de Junções Íntimas/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Arginina/administração & dosagem , Células Cultivadas , Dieta/veterinária , Relação Dose-Resposta a Droga , Enterócitos/fisiologia , Regulação da Expressão Gênica/efeitos dos fármacos , Transdução de Sinais , Proteínas de Junções Íntimas/genética
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