Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 12.131
Filtrar
1.
Chem Biol Interact ; 328: 109195, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32707044

RESUMO

A previous study demonstrated that glutathione (GSH) produces specific antidepressant-like effect in the forced swimming test (FST), a predictive test of antidepressant activity. The present study investigated the involvement of multiple cellular targets implicated in the antidepressant-like effect of GSH in the FST. The antidepressant-like effect of GSH (300 nmol/site, icv) lasted up to 3 h when mice were submitted to FST. The central administration of oxidized GSH (GSSG, 3-300 nmol/site) did not alter the behavior of mice submitted to the FST. Furthermore, the combined treatment of sub-effective doses of GSH (100 nmol/site, icv) with a sub-effective dose of classical antidepressants (fluoxetine 10 mg/kg, and imipramine 5 mg/kg, ip) presented synergistic effect by decreasing the immobility time in the FST. The antidepressant-like effect of GSH was abolished by prazosin (1 mg/kg, ip, α1-adrenoceptor antagonist), baclofen (1 mg/kg, ip, GABAB receptor agonist), bicuculline (1 mg/kg, ip, GABAA receptor antagonist), l-arginine (750 mg/kg, ip, NO precursor), SNAP (25 µg/site, icv, NO donor), but not by yohimbine (1 mg/kg, ip, α2-adrenoceptor antagonist). The NMDA receptor antagonists, MK-801(0.001 mg/kg, ip) or GMP (0.5 mg/kg, ip), potentiated the effect of a sub-effective dose of GSH in the FST. These results suggest that the antidepressant-like effect induced by GSH is connected to the activation of α1 adrenergic and GABAA receptors, as well as the inhibition of GABAB and NMDA receptors and NO biosyntesis. We speculate that redox-mediated signaling on the extracelular portion of cell membrane receptors would be a common mechanism of action of GSH.


Assuntos
Antidepressivos/farmacologia , Glutationa/farmacologia , Terapia de Alvo Molecular , Antagonistas Adrenérgicos/farmacologia , Animais , Arginina/farmacologia , Sinergismo Farmacológico , Feminino , Glutationa/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Imobilização , Masculino , Camundongos , Receptores Adrenérgicos/metabolismo , Receptores de GABA/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/metabolismo , S-Nitroso-N-Acetilpenicilamina/farmacologia , Natação
2.
Hum Cell ; 33(3): 590-598, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32474770

RESUMO

Cell lines are powerful tools for research into liver function at the molecular level. However, they are generally unsuitable for rigorously assessing the effects of amino acid composition, because many lines require serum-containing medium for their maintenance. Here, we aimed to investigate the effects of ornithine and arginine, which are included in the characteristic metabolic process in hepatocyte, on a human hepatoma-derived cell line (FLC-4) that can be cultured in serum-free medium. FLC-4 cells were cultured under the following three conditions: + ornithine/ - arginine, - ornithine/ - arginine, and -ornithine/ + arginine. Albumin expression evaluated by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay and showed no obvious differences based on the presence of ornithine or arginine. However, the mRNA levels of two liver-enriched transcription factors (CEBPB and HNF1A), which are involved in regulating albumin expression, were significantly higher in cells grown in medium-containing arginine than that in cells grown in ornithine-containing medium. Western blotting showed that the levels both activating and inhibitory C/EBPß isoforms were significantly increased in cells grown in arginine medium. Furthermore, we have found that depletion of both ornithine and arginine, the polyamine sources, in the medium did not cause polyamine deficiency. When ornithine and arginine were depleted, albumin production was significantly reduced at the mRNA level, CEBPB mRNA levels were increased, and the level of activating form of C/EBPß was increased. The results of this study suggest that in hepatocyte, these two amino acids might have different functions, and because of which they elicit disparate cellular responses.


Assuntos
Aminoácidos/farmacologia , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Carcinoma Hepatocelular/genética , Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/genética , Albumina Sérica Humana/genética , Albumina Sérica Humana/metabolismo , Arginina/farmacologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Meios de Cultura , Hepatócitos/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Ornitina/farmacologia , RNA Mensageiro/metabolismo
3.
Proc Natl Acad Sci U S A ; 117(27): 15862-15873, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32561647

RESUMO

Albuminuria is an independent risk factor for the progression to end-stage kidney failure, cardiovascular morbidity, and premature death. As such, discovering signaling pathways that modulate albuminuria is desirable. Here, we studied the transcriptomes of podocytes, key cells in the prevention of albuminuria, under diabetic conditions. We found that Neuropeptide Y (NPY) was significantly down-regulated in insulin-resistant vs. insulin-sensitive mouse podocytes and in human glomeruli of patients with early and late-stage diabetic nephropathy, as well as other nondiabetic glomerular diseases. This contrasts with the increased plasma and urinary levels of NPY that are observed in such conditions. Studying NPY-knockout mice, we found that NPY deficiency in vivo surprisingly reduced the level of albuminuria and podocyte injury in models of both diabetic and nondiabetic kidney disease. In vitro, podocyte NPY signaling occurred via the NPY2 receptor (NPY2R), stimulating PI3K, MAPK, and NFAT activation. Additional unbiased proteomic analysis revealed that glomerular NPY-NPY2R signaling predicted nephrotoxicity, modulated RNA processing, and inhibited cell migration. Furthermore, pharmacologically inhibiting the NPY2R in vivo significantly reduced albuminuria in adriamycin-treated glomerulosclerotic mice. Our findings suggest a pathogenic role of excessive NPY-NPY2R signaling in the glomerulus and that inhibiting NPY-NPY2R signaling in albuminuric kidney disease has therapeutic potential.


Assuntos
Albuminúria/metabolismo , Nefropatias/metabolismo , Neuropeptídeo Y/metabolismo , Receptores de Neuropeptídeo Y/metabolismo , Transdução de Sinais/fisiologia , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Benzazepinas/farmacologia , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas , Modelos Animais de Doenças , Regulação para Baixo , Doxorrubicina/farmacologia , Humanos , Insulina/metabolismo , Nefropatias/patologia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Neuropeptídeo Y/farmacologia , Neuropeptídeo Y/urina , Podócitos/metabolismo , Proteômica , Receptores de Neuropeptídeo Y/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
4.
Food Chem ; 318: 126516, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32146313

RESUMO

This work investigated the effects of L-arginine (Arg) and L-lysine (Lys) on the tenderness of chicken breast and explored the possible mechanisms underlying this effect for the first time. The results showed that both Arg and Lys decreased the shear force and increased the pH value, sarcomere length and myofibrillar fragmentation index as well as degraded the troponin-T by keeping calpain activity in chicken breast. In addition, Arg effectively reduced Ca2+/Mg2+-ATPase activities and promoted actomyosin dissociation. These results indicated that both Arg and Lys could enhance the tenderness of chicken breast, and it could also explain why Arg was more effective than Lys in improving the tenderness of chicken breast. These results will help facilitate the development of industrial-scale methods for improving the tenderness of meat products.


Assuntos
Actomiosina/química , Arginina/farmacologia , Galinhas , Lisina/farmacologia , Produtos Avícolas , Troponina T/química , Animais , Arginina/química , Calpaína/química , Calpaína/metabolismo , Qualidade dos Alimentos , Concentração de Íons de Hidrogênio , Lisina/química
5.
Nihon Yakurigaku Zasshi ; 155(2): 62-68, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32115479

RESUMO

The EDRF discovered in 1986 by Furchgott was later identified as NO by Ignarro. NO was a widely noted gas with diverse functions, having arginine (L-Arg) as a substrate for the NO synthase (NOS). L-Arg and L-citrulline (L-Cit) have long been associated with the urea cycle. L-Cit was produced with NO by the reaction of L-Arg and oxygen. It was shown that administration of L-Arg in animals and humans caused vasodilation and anti-arteriosclerosis effects. Despite the arginine paradox ratio of intracellular arginine concentration to the Km value of NOS gaining widespread attention, advanced arteriosclerosis is known to reduce vascular reactivity towards L-Arg. In recent years, the anti-arteriosclerosis and anti-cell aging effects of the reactive substance citrulline (L-Cit) have been studied. L-Cit and L-Arg combination therapy are starting to be considered in various clinical applications as well.


Assuntos
Envelhecimento/fisiologia , Aterosclerose/prevenção & controle , Óxido Nítrico/fisiologia , Animais , Arginina/farmacologia , Aterosclerose/patologia , Citrulina/farmacologia , Humanos , Óxido Nítrico Sintase , Vasodilatação
6.
J Dairy Sci ; 103(5): 4754-4764, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32197854

RESUMO

The development of the small intestine (SI) is important for the health and growth of neonatal calves. This study evaluated the effect of arginine (Arg) and glutamine (Gln) supplementation and 2 levels of milk allowance on the histomorphological development of the SI in preweaning calves. Sixty mixed-sex Friesian × Jersey calves (3-5 d of age) were offered reconstituted whole milk (125 g/L, 26% fat, 26% protein) at either high (20% of arrival body weight/d; HM) or low (10% of arrival body weight/d; LM) milk allowance without (Ctrl) or with supplementary Arg or Gln (at 1% of milk dry matter) in a 2 × 3 factorial design (n = 10/treatment). After 35 d on the diets, all calves were slaughtered to collect tissues for examination of SI development. Calves in the HM group had higher milk intake, total weight gain, and average daily gain compared with LM calves, but no effect of AA supplementation nor an interaction between milk allowance and AA supplementation was observed. For the duodenum, we observed an AA by milk allowance interaction for villus height and width, and goblet cell number per villus (HM-Arg > HM-Gln > HM-Ctrl), and villus height to crypt depth ratio (HM-Arg > HM-Gln = HM-Ctrl), but no effect of AA supplementation in the LM group. Goblet cell numbers per 100 µm of SI were greater in Arg-supplemented calves than in unsupplemented controls, with Gln-supplemented calves intermediate to but not different from the other groups. Epithelium thickness was greater in LM than in HM calves. Villus density, crypt depth, and muscle thickness did not differ between groups. For the jejunum, there was an AA by milk allowance interaction for villus height, villus surface area, and villus height to crypt depth ratio (HM-Arg = HM-Gln > HM-Ctrl), with no effect of AA supplementation in the LM groups. Amino acid supplementation affected goblet cell number per villus (HM-Gln > HM-Ctrl calves, HM-Arg intermediate), and both LM-Arg and LM-Gln calves had greater numbers than LM-Ctrl calves. Villus width, crypt depth, and muscle thickness were greater in HM than LM calves but there was no effect of AA supplementation. Villus density, goblet cell number per 100 µm of SI, and epithelium thickness were unaffected by AA supplementation and milk allowance. Milk allowance and AA supplementation had no effect on SI morphology in the ileum. Increasing milk allowance improved villus height, width, and surface area but only in Arg- or Gln-supplemented calves, not in control calves. The observed changes in development may be important for intestinal functionality, integrity, and barrier function in preweaning calves, potentially through increased cell growth and proliferation or reduced levels of cellular atrophy.


Assuntos
Ração Animal , Arginina/farmacologia , Bovinos/crescimento & desenvolvimento , Suplementos Nutricionais , Glutamina/farmacologia , Intestino Delgado/crescimento & desenvolvimento , Leite , Animais , Peso Corporal , Dieta/veterinária , Feminino , Mucosa Intestinal/crescimento & desenvolvimento , Intestino Delgado/metabolismo , Masculino , Ganho de Peso
7.
Paediatr Drugs ; 22(3): 279-293, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32140997

RESUMO

Supplemental arginine has shown promise as a safe therapeutic option to improve endogenous nitric oxide (NO) regulation in cardiovascular diseases associated with endothelial dysfunction. In clinical studies in adults, L-arginine, an endogenous amino acid, was reported to improve cardiovascular function in hypertension, pulmonary hypertension, preeclampsia, angina, and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) syndrome. L-citrulline, a natural precursor of L-arginine, is more bioavailable than L-arginine because it avoids hepatic first-pass metabolism and has a longer circulation time. Although not yet well-studied, arginine/citrulline has immense therapeutic potential in some life-threatening diseases in children. However, the optimal clinical development of arginine or citrulline in children requires more information about pharmacokinetics and exposure-response relationships at appropriate ages and under relevant disease states. This article summarizes the preclinical and clinical studies of arginine/citrulline in both adults and children, including currently available pharmacokinetic information. The pharmacology of arginine/citrulline is confounded by several patient-specific factors such as variations in baseline arginine/citrulline due to developmental ages and disease states. Currently available pharmacokinetic studies are insufficient to inform the optimal design of clinical studies, especially in children. Successful bench-to-bedside clinical translation of arginine supplementation awaits information from well-designed pharmacokinetic/pharmacodynamic studies, along with pharmacometric approaches.


Assuntos
Arginina/uso terapêutico , Citrulina/uso terapêutico , Farmacologia Clínica/métodos , Adolescente , Adulto , Arginina/farmacologia , Criança , Citrulina/farmacologia , Feminino , Humanos , Masculino , Adulto Jovem
8.
Rev Col Bras Cir ; 46(6): e20192322, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32022111

RESUMO

OBJECTIVE: to evaluate the effects of arginine on abdominal wall healing in rats. METHODS: we submitted 20 Wistar rats to laparotomy and divided them into two groups, arginine and control, which then received, respectively, daily intraperitoneal treatment with arginine (300mg/kg/day) and weight-equivalent phosphate buffered solution, during five days. On the seventh postoperative day, we collected blood and scar wall samples from both groups. We evaluated serum nitrate and nitrite levels, wound evolution by tissue hydroxyproline dosages, granulation tissue formation, percentage of mature and immature collagen, myofibroblast density and angiogenesis. We used the ANOVA and the Student's t tests with p=0.05 for comparisons between groups. RESULTS: there were no significant differences between the groups studied for nitrate and nitrite (p=0.9903), tissue hydroxyproline (p=0.1315) and myofibroblast density (p=0.0511). The arginine group presented higher microvascular density (p=0.0008), higher percentage of type I collagen (p=0.0064) and improved granulation tissue formation, with better angiofibroblastic proliferation rates (p=0.0007) and wound edge reepithelization (p=0.0074). CONCLUSION: in the abdominal wall healing evaluation of Wistar rats under arginine treatment, there was no change in serum nitrate and nitrite levels, total collagen deposition and myofibroblast density. There was an increase in type I collagen maturation, microvascular density and improvement in scar granulation tissue formation by better edge reepithelization and angiofibroblastic proliferation.


Assuntos
Parede Abdominal/cirurgia , Arginina/farmacologia , Colágeno/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Traumatismos Abdominais/tratamento farmacológico , Parede Abdominal/patologia , Animais , Colágeno/metabolismo , Modelos Animais , Miofibroblastos/efeitos dos fármacos , Ratos , Ratos Wistar
9.
J Int Soc Sports Nutr ; 17(1): 12, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093766

RESUMO

BACKGROUND: Athletes are increasingly exploring ways to enhance their physical performance. Increasing blood flow to the working tissues through endothelium-dependent vasodilation is one factor athletes use to realize these results. Sports supplements such as pre-workouts tout this benefit; however, many have not been tested under laboratory conditions to examine the effects of commonly used supplements on vasodilation. Two popular supplements are Nitrosigine® and citrulline malate (CM). Thus, the purpose of this experiment was to determine the effects of Nitrosigine and CM on vasodilation using ultrasound and flow mediated dilation (FMD). METHODS: Healthy, normotensive, and physically active male (n = 16) and female (n = 8) young adults participated in the present investigation. We utilized a randomized, double-blind, within-subjects design where participants reported for three trials, each preceded by a 7-day washout period. Baseline FMD measurement was obtained for each visit, followed by consumption of one clinical dose CM (8 g), Nitrosigine (1.5 g), or dextrose placebo (8 g). Following a 60-min digestion period, FMD was repeated. Supplementation order was randomized controlling for potential order effects. RESULTS: Repeated measures ANOVA yielded a significant supplement (3) x time (2) effect (p < .001), such that Nitrosigine and CM yielded a greater improvement in FMD response than placebo. After supplementation, Nitrosigine and CM increased FMD by 31 and 34%, respectively, compared to a decrease of 2% during the placebo trial. After allometric scaling of the FMD values, supplement x time effect remained significant (p = .001) and changes were similar to non-scaled results. Nitrosigine (23%) and CM (25%) generated significantly greater allometric scaled FMD values when compared to the placebo trial (0.60%). DISCUSSION: Both Nitrisigine and CM increased endothelial-dependent vasodilation as measured by a change in FMD. Increased vasodilation leads to an increase in skeletal muscle blood flow resulting in potential improvements in exercise performance.


Assuntos
Arginina/farmacologia , Citrulina/análogos & derivados , Suplementos Nutricionais , Inositol/farmacologia , Malatos/farmacologia , Silicatos/farmacologia , Vasodilatação/efeitos dos fármacos , Adolescente , Adulto , Citrulina/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Voluntários Saudáveis , Humanos , Masculino , Ultrassonografia , Adulto Jovem
10.
Int J Food Microbiol ; 320: 108519, 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31962221

RESUMO

A novel composite antimicrobial film (CAF), made from a pullulan-based biopolymer and polyethylene (PE) was developed and evaluated for controlling pathogens associated with muscle foods. Initially, CAFs were developed by incorporating thymol (T), nisin (N) and/or lauric arginate (LAE) into the pullulan layer and layering it on top of PE. The antimicrobial activity of the resulting CAFs was evaluated against cocktails of Shiga toxin-producing E. coli (STEC), Salmonella spp., Listeria monocytogenes (L. monocytogenes) and Staphylococcus aureus (S. aureus) in disk diffusion assays (DDAs). CAFs containing N were ineffective, while those containing T were effective for inhibiting the pathogens in DDAs. However, CAFs made with them did not exhibit desirable physical and mechanical properties since solvents (HCl and ethanol, respectively) interfered with the binding of pullulan to PE. Conversely, CAFs made with 0.5, 1 and 2.5% LAE maintained proper physical and mechanical characteristics and inhibited the four bacterial pathogens in DDAs. Based on these preliminary results, cocktails consisting of approximately 8 log10 CFU/ml of STEC, Salmonella, L. monocytogenes, or S. aureus were experimentally-inoculated onto raw beef, raw chicken breast, or ready-to-eat (RTE) turkey breast to obtain approximately 6.6 log10 CFU/cm2, aseptically transferred to CAFs containing 0.5, 1, or 2.5% LAE that were made into sachets/bags, vacuum packaged, sealed, and remaining microbial populations determined up to 28 days of refrigerated storage (4 °C). By day 28, CAFs containing 0.5, 1, and 2.5% LAE reduced: STEC by 1.13, 1.33 and 2.88 log10 CFU/cm2 respectively, on raw beef; Salmonella by 2.03, 2.12 and 3.01 log10 CFU/cm2 respectively, on raw chicken breast; L. monocytogenes by 1.12, 1.81 and 3.56 log10 CFU/cm2 respectively, on RTE turkey breast; and S. aureus by 0.68, 2.02 and 3.43 log10 CFU/cm2, respectively, on RTE turkey breast. CAFs may be of interest to the meat and poultry industry to control foodborne pathogens associated with these food products.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Embalagem de Alimentos/instrumentação , Carne/microbiologia , Animais , Arginina/análogos & derivados , Arginina/química , Arginina/farmacologia , Bactérias/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Embalagem de Alimentos/métodos , Glucanos/química , Glucanos/farmacologia , Nisina/química , Nisina/farmacologia , Timol/química , Timol/farmacologia
11.
J Exp Clin Cancer Res ; 39(1): 11, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931851

RESUMO

BACKGROUND: Mounting evidence suggests that complement components promote tumor progression via modulating immune suppression, angiogenesis, or tumor cell proliferation. However, the role of C3a-C3aR signaling in regulating lung metastasis of breast cancer remains unknown. METHODS: We performed various ex-vivo and in-vivo assays. Genetic and pharmacological C3aR blockade models were applied to investigate the role of C3a-C3aR in metastasis of breast cancer. RESULTS: C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Mechanically, C3a-C3aR signaling augments pro-metastatic cytokine secretion and extracellular matrix components expression of CAFs via the activation of PI3K-AKT signaling. Genetic or pharmacological blockade of C3aR signaling effectively inhibited lung metastasis of breast cancer in mouse models. CONCLUSIONS: C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Targeting C3aR signaling is a potential anti-metastasis strategy for breast cancer therapy.


Assuntos
Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/metabolismo , Complemento C3/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Receptores de Complemento/metabolismo , Animais , Arginina/administração & dosagem , Arginina/análogos & derivados , Arginina/farmacologia , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Fibroblastos Associados a Câncer/efeitos dos fármacos , Linhagem Celular Tumoral , Complemento C3/genética , Citocinas/genética , Citocinas/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Camundongos , Invasividade Neoplásica , Transplante de Neoplasias , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Complemento/genética , Transdução de Sinais
12.
J Med Chem ; 63(2): 529-541, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31910011

RESUMO

Structure-activity relationships for a series of small-molecule thiophenes resulted in potent and selective antagonism of human Complement C3a receptor. The compounds are about 100-fold more potent than the most reported antagonist SB290157. A new compound JR14a was among the most potent of the new antagonists in vitro, assessed by (a) inhibition of intracellular calcium release (IC50 10 nM) induced in human monocyte-derived macrophages by 100 nM C3a, (b) inhibition of ß-hexosaminidase secretion (IC50 8 nM) from human LAD2 mast cells degranulated by 100 nM C3a, and (c) selectivity for human C3aR over C5aR. JR14a was metabolically stable in rat plasma and in rat liver microsomes and efficacious in rats when given orally to suppress rat paw inflammation, macrophage and mast cell activation, and histopathology induced by intraplantar paw administration of a C3aR agonist. Potent C3aR antagonists are now available for interrogating C3a receptor activation and suppressing C3aR-mediated inflammation in mammalian physiology and disease.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Arginina/análogos & derivados , Compostos Benzidrílicos/farmacologia , Complemento C3a , Receptores de Complemento/antagonistas & inibidores , Tiofenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacocinética , Arginina/farmacocinética , Arginina/farmacologia , Compostos Benzidrílicos/farmacocinética , Cálcio/metabolismo , Hexosaminidases/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Mastócitos , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Ratos , Ratos Wistar , Bibliotecas de Moléculas Pequenas , Relação Estrutura-Atividade , Tiofenos/síntese química , Tiofenos/farmacocinética
13.
Carbohydr Polym ; 230: 115640, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887895

RESUMO

Bone transplantations are still facing many serious challenges, hydrogel as a new kind of artificial bone substitutes has developed into a promising bone scaffold material. However, it is still a challenge to combine bioactive agents and hydrogel matrix to promote osteoinductivity. Herein, we developed a novel bioactive hydrogel based on arginine-based unsaturated poly (ester amide) (Arg-UPEA) and methacrylated hyaluronic acid (HA-MA) via photo-crosslinking. As the results indicated, we found that the introduction of Arg-UPEA into HA-MA hydrogels could finely modulate their compressive modulus, swelling level and porous structure. Besides, among groups of different feed ratio, groups of 10 % and 15 % of Arg-UPEA content effectively enhanced osteogenic differentiation in osteoblasts when compared with HA-MA hydrogel. Furthermore, better bone regeneration and expression of osteogenesis-related factors in vivo also verified the Arg-UPEA/HA-MA hybrid hydrogels as a promising scaffold material for bone tissue engineering.


Assuntos
Substitutos Ósseos/química , Hidrogéis/química , Engenharia Tecidual , Tecidos Suporte/química , Células 3T3 , Amidas/química , Amidas/farmacologia , Animais , Arginina/química , Arginina/farmacologia , Regeneração Óssea , Substitutos Ósseos/uso terapêutico , Osso e Ossos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Hidrogéis/uso terapêutico , Interações Hidrofóbicas e Hidrofílicas , Metacrilatos/química , Metacrilatos/farmacologia , Camundongos , Células NIH 3T3 , Osteogênese/fisiologia , Poliésteres/química , Poliésteres/farmacologia , Porosidade , Ratos Sprague-Dawley
14.
J Strength Cond Res ; 34(5): 1480-1495, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31977835

RESUMO

Gonzalez, AM and Trexler, ET. Effects of citrulline supplementation on exercise performance in humans: A review of the current literature. J Strength Cond Res 34(5): 1480-1495, 2020-L-citrulline, a nonessential amino acid found primarily in watermelon, has recently garnered much attention for its potential to augment L-arginine bioavailability, nitric oxide production, and exercise performance. Over the past decade, L-citrulline has received considerable scientific attention examining potentially ergogenic properties for both aerobic and anaerobic exercise performance. Thus, the purpose of this article is to summarize the theoretical rationale behind L-citrulline supplementation and to comprehensively review the available scientific evidence assessing the potential ergogenic value of L-citrulline supplementation on vascular function and exercise performance in humans. In addition, research that has investigated the potential synergistic effects of L-citrulline with other dietary ingredients (e.g., arginine, antioxidants, nitrates, and branched-chain amino acids) is reviewed. Oral L-citrulline and citrulline malate supplementation have shown to increase plasma citrulline and arginine concentrations, along with total nitrate and nitrite concentrations. Although blood flow enhancement is a proposed mechanism for the ergogenic potential of L-citrulline, evidence supporting acute improvements in vasodilation and skeletal muscle tissue perfusion after supplementation is scarce and inconsistent. Nevertheless, several studies have reported that L-citrulline supplementation can enhance exercise performance and recovery. Given the positive effects observed from some investigations, future studies should continue to investigate the effects of both acute and chronic supplementation with L-citrulline and citrulline malate on markers of blood flow and exercise performance and should seek to elucidate the mechanism underlying such effects.


Assuntos
Citrulina/farmacologia , Suplementos Nutricionais , Exercício Físico/fisiologia , Músculo Esquelético/efeitos dos fármacos , Aminoácidos de Cadeia Ramificada/farmacologia , Antioxidantes/farmacologia , Arginina/farmacologia , Biomarcadores , Citrulina/análogos & derivados , Quimioterapia Combinada , Humanos , Malatos/farmacologia , Músculo Esquelético/fisiologia , Nitratos/farmacologia
15.
Int J Food Microbiol ; 315: 108417, 2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-31715542

RESUMO

Lauric arginate (LAE, ethyl-Nα-lauroyl-L-arginate hydrochloride) is synthesized from food components lauric acid and L-arginine and is quickly hydrolyzed to lauric acid and L-arginine in vivo. The antimicrobial properties and low toxicity are the basis for approval as a generally recognized as safe (GRAS) preservative at a level of up to 200 ppm in certain food products in the United States such as meat, poultry, and cheese and a safe food preservative up to 225 ppm in the European Union. These developments have generated great interest to apply LAE to improve the safety and quality of food products. In the present review, physicochemical and toxicological properties are first discussed. Antimicrobial properties and mechanisms of LAE in microbiological media, and antimicrobials used in combination with LAE aiming to achieve synergistic activities are then reviewed. The physical basis of reduced antimicrobial activities of LAE in food matrices is discussed, and studies applying LAE in meat, poultry, dairy, produce, and low-moisture foods and food-contact surfaces are summarized. Antimicrobial properties of LAE in emulsion systems and potential packaging films are also discussed for potential novel applications to improve the application in food systems. Finally, the possible impact of LAE on food sensory properties is reviewed along with some perspectives on research needs in the science and technology of LAE for use as a food antimicrobial preservative.


Assuntos
Antibacterianos/farmacologia , Arginina/análogos & derivados , Microbiologia de Alimentos/métodos , Conservantes de Alimentos/farmacologia , Animais , Arginina/farmacologia , Queijo/microbiologia , Carne/microbiologia , Aves Domésticas/microbiologia
16.
Chem Commun (Camb) ; 56(4): 615-618, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31833497

RESUMO

Three model arginine-rich tripeptides RXR (X = W, F or non-natural residue 2-napthylalanine) were investigated as antimicrobial agents, with a specific focus to target Pseudomonas aeruginosa through membrane lysis. Activity against biofilms was related to binding of the second messenger molecule, nucleotide bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP). Strong selective activity against P. aeruginosa in planktonic form was observed for RFR and RWR.


Assuntos
Antibacterianos/farmacologia , Arginina/farmacologia , Oligopeptídeos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Arginina/química , Biofilmes/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Humanos , Modelos Moleculares , Oligopeptídeos/síntese química , Oligopeptídeos/química
17.
Int J Vitam Nutr Res ; 90(1-2): 17-22, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30982443

RESUMO

Purpose: In inflammatory bowel disease increased asymmetric dimethylarginine (ADMA) levels could inhibit nitric oxide (NO) synthase. Vitamin D may increase activity and expression of endothelial NO synthase, which could be done through its possible mechanism of decreasing ADMA levels. The aim of this study is to investigate the possible effect of Vitamin D3 on serum ADMA levels in ulcerative colitis (UC) patients. Methods: Ninety mild to moderate UC patients were randomized. Each patient received one single muscular injection of 300,000 IU (7500 µg) Vitamin D3 (Vitamin D group) or 1 ml normal saline (Placebo group). At baseline and 90 days after the intervention measurements were done. Data were analyzed using independent t-test and analysis of covariance. Baseline correlations were assessed by Pearson and Spearman correlation coefficients. Results: Following data analysis of 86 participants (40 in placebo and 46 in vitamin D group), there was no correlation between baseline ADMA with baseline vitamin D, ESR and hs-CRP at baseline (p = 0.77) and at the end of study (p = 0.82). Serum ADMA levels were not statistically different between two groups. Adjustment for baseline ADMA levels and baseline body mass index (BMI) did not change the results. With subgroup analyses based on gender and vitamin D level no statistical differences in ADMA levels between two groups were found. Conclusions: In this study, we found no significant changes in serum ADMA levels 3 months following a high dose vitamin D administration in mild to moderate UC patients. Further studies in vitamin D deficient patients are needed.


Assuntos
Colite Ulcerativa , Vitamina D , Vitaminas/farmacologia , Arginina/análogos & derivados , Arginina/química , Arginina/farmacologia , Colite Ulcerativa/fisiopatologia , Humanos , Vitamina D/farmacologia
18.
Food Chem ; 306: 125616, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31622832

RESUMO

This research aimed to explore the role of protein S-nitrosylation in regulating the tenderness of postmortem beef, from the perspective of µ-calpain autolysis and protein proteolysis. Five bovine semimembranosus muscles were incubated with three treatments including S-nitrosoglutathione (GSNO, nitric oxide donor), normal saline and Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME, nitric oxide synthase inhibitor). The results showed that the level of protein S-nitrosylation was improved by GSNO treatment and reduced by L-NAME treatment (p < 0.05). Compared to the control, GSNO treatment had higher shear force while L-NAME treatment presented lower shear force at 7 d postmortem (p < 0.05). In addition, µ-calpain autolysis, myofibrillar protein and desmin degradation were reduced by GSNO treatment and accelerated by L-NAME treatment (p < 0.05). Therefore, it can be speculated that protein S-nitrosylation could affect beef tenderization by regulating the autolysis of µ-calpain and the degradation of myofibrillar proteins.


Assuntos
Proteína S/metabolismo , Carne Vermelha , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Calpaína/metabolismo , Bovinos , Desmina/metabolismo , Proteína S/química , Proteólise
19.
Prostate ; 80(1): 28-37, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573117

RESUMO

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a disorder that is characterized by persistent pelvic pain in men of any age. Although several studies suggest that the transient receptor potential vanilloid 1 (TRPV1) channel is involved in various pathways of chronic pain, the TRPV1 channel has not been implicated in chronic pelvic pain associated with CP/CPPS. METHODS: Male C57BL/6J (B6) and TRPV1 knockout (TRPV1 KO) mice (5-7 weeks old) were used to study the development of pelvic allodynia in a murine model of CP/CPPS called experimental autoimmune prostatitis (EAP). The prostate lobes, dorsal root ganglia (DRG), and spinal cord were excised at day 20. The prostate lobes were assessed for inflammation, TRPV1 expression, and mast cell activity. DRG and spinal cord, between the L6-S4 regions, were analyzed to determine the levels of phosphorylated ERK1/2 (p-ERK 1/2). To examine the therapeutic potential of TRPV1, B6 mice with EAP received intraurethral infusion of a TRPV1 antagonist at day 20 (repeated every 2 days) and pelvic pain was evaluated at days 20, 25, 30, and 35. RESULTS: Our data showed that B6 mice with EAP developed pelvic tactile allodynia at days 7, 14, and 20. In contrast, TRPV1 KO mice with EAP do not develop pelvic tactile allodynia at any time point. Although we observed no change in the levels of TRPV1 protein expression in the prostate from B6 mice with EAP, there was evidence of significant inflammation and elevated mast cell activation. Interestingly, the prostate from TRPV1 KO mice with EAP showed a lack of mast cell activation despite evidence of prostate inflammation. Next, we observed a significant increase of p-ERK1/2 in the DRG and spinal cord from B6 mice with EAP; however, p-ERK1/2 expression was unaltered in TRPV1 KO mice with EAP. Finally, we confirmed that intraurethral administration of a TRPV1 antagonist peptide reduced pelvic tactile allodynia in B6 mice with EAP after day 20. CONCLUSIONS: We demonstrated that in a murine model of CP/CPPS, the TRPV1 channel is key to persistent pelvic tactile allodynia and blocking TRPV1 in the prostate may be a promising strategy to quell chronic pelvic pain.


Assuntos
Doenças Autoimunes/metabolismo , Prostatite/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Gânglios Espinais/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/imunologia , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Masculino , Mastócitos/imunologia , Mastócitos/metabolismo , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oligopeptídeos/farmacologia , Dor Pélvica/tratamento farmacológico , Dor Pélvica/imunologia , Dor Pélvica/metabolismo , Dor Pélvica/patologia , Fosforilação , Prostatite/tratamento farmacológico , Prostatite/imunologia , Prostatite/patologia , Medula Espinal/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/deficiência
20.
J Physiol Pharmacol ; 70(4)2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31741458

RESUMO

We showed previously that in anaesthetized rats acute noninvasive renal denervation (DNX) induced an increase in arterial blood pressure (MABP), unlike the usual hypotensive effect. Here we aimed to establish the background of such unusual response, especially the role of oxidative stress as suggested by an earlier study. The contribution of oxidative stress was explored by studying the effects on DNX-induced MABP increase of pretreatment with 4-hydroxy-3-methoxyacetophenone (apocynin, APO), a powerful antioxidant and antihypertensive agent, and N(omega)-propyl-L-arginine (L-NPA), a blocker of neuronal nitric oxide synthase (nNOS). In anaesthetized Wistar rats maintained on standard (STD) or high-salt (HS) diet sequential right- and left-side DNX was performed. MABP responses were examined without pretreatment and after APO (20 mg/day on two preceding days) and L-NPA (1 mg/kg/h throughout experiment), given alone or combined. In untreated rats, bilateral DNX increased MABP by 6% on STD and 15% on HS diet (P < 0.01 or less); the difference between MABP responses was highly significant (P = 0.002). In STD rats APO or APO + L-NPA treatment failed to alter post-DNX MABP increases whereas L-NPA alone reversed the response and a significant 7% decrease occurred. In HS rats APO and L-NPA given alone reversed the MABP response and significant decreases of 14% (P = 0.001) and 8% (P = 0.01), were seen. Surprisingly, with L-NPA + APO pretreatment only abolishment (not reversal) of post-DNX pressure increase occurred. The results suggest that both systemic, intrarenal and brain oxidative stress, and excessive nNOS activity, mostly in the brain, determine the unexpected post-DNX pressure increase.


Assuntos
Pressão Sanguínea , Denervação , Rim/inervação , Óxido Nítrico Sintase Tipo I/fisiologia , Estresse Oxidativo , Acetofenonas/farmacologia , Anestesia , Animais , Arginina/análogos & derivados , Arginina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Sódio na Dieta/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA