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1.
Mol Genet Metab ; 141(3): 108112, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301530

RESUMO

OBJECTIVE: Liver transplantation (LTx) is an intervention when medical management is not sufficiently preventing individuals with urea cycle disorders (UCDs) from the occurrence of hyperammonemic events. Supplementation with L-citrulline/arginine is regularly performed prior to LTx to support ureagenesis and is often continued after the intervention. However, systematic studies assessing the impact of long-term L-citrulline/arginine supplementation in individuals who have undergone LTx is lacking to date. METHODS: Using longitudinal data collected systematically, a comparative analysis was carried out by studying the effects of long-term L-citrulline/arginine supplementation vs. no supplementation on health-related outcome parameters (i.e., anthropometric, neurological, and cognitive outcomes) in individuals with UCDs who have undergone LTx. Altogether, 52 individuals with male ornithine transcarbamylase deficiency, citrullinemia type 1 and argininosuccinic aciduria and a pre-transplant "severe" disease course who have undergone LTx were investigated by using recently established and validated genotype-specific in vitro enzyme activities. RESULTS: Long-term supplementation of individuals with L-citrulline/arginine who have undergone LTx (n = 16) does neither appear to alter anthropometric nor neurocognitive endpoints when compared to their severity-adjusted counterparts that were not supplemented (n = 36) after LTx with mean observation periods between four to five years. Moreover, supplementation with L-citrulline/arginine was not associated with an increase of disease-specific plasma arithmetic mean values for the respective amino acids when compared to the non-supplemented control cohort. CONCLUSION: Although supplementation with L-citrulline/arginine is often continued after LTx, this pilot study does neither identify altered long-term anthropometric or neurocognitive health-related outcomes nor does it find an adequate biochemical response as reflected by the unaltered plasma arithmetic mean values for L-citrulline or L-arginine. Further prospective analyses in larger samples and even longer observation periods will provide more insight into the usefulness of long-term supplementation with L-citrulline/arginine for individuals with UCDs who have undergone LTx.


Assuntos
Transplante de Fígado , Distúrbios Congênitos do Ciclo da Ureia , Masculino , Humanos , Citrulina/uso terapêutico , Arginina/metabolismo , Projetos Piloto , Distúrbios Congênitos do Ciclo da Ureia/tratamento farmacológico , Distúrbios Congênitos do Ciclo da Ureia/cirurgia , Suplementos Nutricionais , Ureia/metabolismo
2.
Br J Nutr ; 131(3): 474-481, 2024 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-37664994

RESUMO

Postmenopausal women have augmented pressure wave responses to low-intensity isometric handgrip exercise (IHG) due to an overactive metaboreflex (postexercise muscle ischaemia, PEMI), contributing to increased aortic systolic blood pressure (SBP). Menopause-associated endothelial dysfunction via arginine (ARG) and nitric oxide deficiency may contribute to exaggerated exercise SBP responses. L-Citrulline supplementation (CIT) is an ARG precursor that decreases SBP, pulse pressure (PP) and pressure wave responses to cold exposure in older adults. We investigated the effects of CIT on aortic SBP, PP, and pressure of forward (Pf) and backward (Pb) waves during IHG and PEMI in twenty-two postmenopausal women. Participants were randomised to CIT (10 g/d) or placebo (PL) for 4 weeks. Aortic haemodynamics were assessed via applanation tonometry at rest, 2 min of IHG at 30 % of maximal strength, and 3 min of PEMI. Responses were analysed as change (Δ) from rest to IHG and PEMI at 0 and 4 weeks. CIT attenuated ΔSBP (−9 ± 2 v. −1 ± 1 mmHg, P = 0·006), ΔPP (−5 ± 2 v. 0 ± 1 mmHg, P = 0·03), ΔPf (−6 ± 2 v. −1 ± 1 mmHg, P = 0·01) and ΔPb (−3 ± 1 v. 0 ± 1 mmHg, P = 0·02) responses to PEMI v. PL. The ΔPP during PEMI was correlated with ΔPf (r = 0·743, P < 0·001) and ΔPb (r = 0·724, P < 0·001). Citrulline supplementation attenuates the increase in aortic pulsatile load induced by muscle metaboreflex activation via reductions in forward and backward pressure wave amplitudes in postmenopausal women.


Assuntos
Pressão Arterial , Citrulina , Humanos , Feminino , Idoso , Pressão Arterial/fisiologia , Citrulina/farmacologia , Pós-Menopausa , Força da Mão , Músculo Esquelético , Pressão Sanguínea , Suplementos Nutricionais
3.
Biotechnol Appl Biochem ; 70(2): 526-536, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35761421

RESUMO

In recent years, arginine deiminase (ADI, EC 3.5.3.6) has attracted much attention as a biocatalyst that produces the functional amino acid l-citrulline from l-arginine and also as an anticancer enzyme. Here, we identified and characterized a putative ADI from the thermophilic bacterium Halothermothrix orenii. The H. orenii ADI (H-ADI) protein was expressed in Escherichia coli BL21(DE3) with a specific activity of 91.8 U/mg protein at 55°C and pH 6.5. The enzyme remained at 74% relative activity after incubation at 45°C for 180 min, only 25% at 50°C. The melting temperature was 56°C. H-ADI is not a metal-requiring enzyme; Ni2+ slightly improved the catalytic activity. The Km and Vmax for l-arginine were 55.5 mM and 156.8 µmol/min/mg protein, respectively. Moreover, three residues (Arg183, Arg237, and His273) were key to the formation of l-citrulline, as analyzed by alanine-scanning mutagenesis. Finally, the enzymatic synthesis of l-citrulline was carried out at 50°C with a conversion ratio reaching 99.03%. Together, these findings show that H-ADI is a promising biocatalyst for the production of l-citrulline.


Assuntos
Citrulina , Hidrolases , Citrulina/química , Citrulina/metabolismo , Hidrolases/química , Arginina
4.
Adv Exp Med Biol ; 1428: 127-148, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37466772

RESUMO

In preeclampsia, the shallow invasion of cytotrophoblast cells to uterine spiral arteries, leading to a reduction in placental blood flow, is associated with an imbalance of proangiogenic/antiangiogenic factors to impaired nitric oxide (NO) production. Proangiogenic factors, such as vascular endothelial growth factor (VEGF) and placental growth factor (PlGF), require NO to induce angiogenesis through antioxidant regulation mechanisms. At the same time, there are increases in antiangiogenic factors in preeclampsia, such as soluble fms-like tyrosine kinase type 1 receptor (sFIt1) and toll-like receptor 9 (TLR9), which are mechanism derivates in the reduction of NO bioavailability and oxidative stress in placenta.Different strategies have been proposed to prevent or alleviate the detrimental effects of preeclampsia. However, the only intervention to avoid the severe consequences of the disease is the interruption of pregnancy. In this scenario, different approaches have been analysed to treat preeclamptic pregnant women safely. The supplementation with amino acids is one of them, especially those associated with NO synthesis. In this review, we discuss emerging concepts in the pathogenesis of preeclampsia to highlight L-arginine and L-citrulline supplementation as potential strategies to improve birth outcomes. Clinical and experimental data concerning L-arginine and L-citrulline supplementation have shown benefits in improving NO availability in the placenta and uterine-placental circulation, prolonging pregnancy in patients with gestational hypertension and decreasing maternal blood pressure.


Assuntos
Pré-Eclâmpsia , Feminino , Gravidez , Humanos , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/metabolismo , Placenta/metabolismo , Citrulina/uso terapêutico , Citrulina/metabolismo , Citrulina/farmacologia , Arginina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator de Crescimento Placentário/metabolismo , Fator de Crescimento Placentário/farmacologia , Suplementos Nutricionais , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo
5.
Stress ; 25(1): 74-86, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34962227

RESUMO

Recent studies have revealed the role of L-citrulline (L-CIT) in thermoregulation, but very little is known about the mechanisms involved. In this study, nitric oxide synthase inhibition and endotoxin-induced fever were used to investigate the effects of L-CIT on body temperature and inflammatory responses. In experiment 1, NW-nitro-L-arginine methyl ester (L-NAME, 150 mg/kg BW), was i. p. injected into chicks fed with basal (CON) or L-CIT diets for 14 days. In experiment 2, Lipopolysaccharide (LPS, 2 mg/kg BW) was i. p. injected following 21d feeding with CON or L-CIT diets. In experiment 3, chickens were injected with either L-NAME, LPS, or L-NAME + LPS following 26 days feeding with CON or L-CIT diets. The rectal (RT), ear (ET), and core body temperature (CBT) of chickens were examined. Results showed that L-NAME effectively decreased the RT, ET, CBT, and plasma NO concentration. In contrast, LPS increased NO levels and initiated hyperthermia by increasing RT, ET, CBT, and PGE2 levels. L-CIT diet reduced the mean CBT in experiment 1 and diminished the NO level, PGE2 level, and mean RT in experiment 3. Co-administration of L-CIT + LPS upregulated IL-6 expression, whereas, LPS injection alone induced IL-10, IL-1ß, and TLR4 gene expressions. Therefore, this study reveals that L-CIT-induced hypothermia was related to NO inhibition and a decrease in PGE2 concentration. Conversely, LPS induced hyperthermia was associated with an increase in both NO and PGE2 concentrations.


Assuntos
Galinhas , Citrulina , Animais , Temperatura Corporal , Galinhas/metabolismo , Citrulina/metabolismo , Citrulina/farmacologia , Dieta , Endotoxinas/farmacologia , Inibidores Enzimáticos/farmacologia , Lipopolissacarídeos/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacologia , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/farmacologia , Estresse Psicológico
6.
Eur J Appl Physiol ; 122(7): 1627-1638, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35429293

RESUMO

INTRODUCTION: Watermelon shows promise as an ergogenic aid due to its high concentration of L-citrulline, vitamins, minerals, and antioxidants. PURPOSE: The purpose of this study was to examine the effect of watermelon supplementation on exercise performance, muscle oxygenation, and vessel diameter. METHODS: In a crossover design fashion, 15 resistance-trained men (22.4 ± 2.9 years; 177.5 ± 7.1 cm; 82.7 ± 11.2 kg) were randomly assigned to supplement with either watermelon juice concentrate (WM; 2.2 g·day-1 L-citrulline) or placebo (PL) for 7 days prior to completing an experimental trial consisting of an isometric mid-thigh pull test and acute bench press protocol. Participants completed two sets of two repetitions at 75% 1 repetition maximum (1-RM) with maximum ballistic intent followed by five repetition-maximum (RM) sets at the same load. Barbell velocity and power were measured via linear position transducer during the first two sets, while volume load and muscle oxygenation were quantified during RM sets. Brachial artery diameter and subjective perception measures were assessed at baseline and immediately pre- and post-exercise. RESULTS: Except for a greater percent change in skeletal muscle oxygenation during WM compared to PL on average and across sets (mean difference = + 4.1%, p = 0.033, BF10 = 2.2-54.5), separate traditional and Bayesian analyses of variance with repeated measures, as well as paired-samples t tests for calculated summary measures, revealed no evidence favoring conditional differences in any measure of performance, perception, or muscle oxygenation. CONCLUSION: Short-term watermelon supplementation does not appear to enhance isometric force production, bench press performance, blood vessel diameter, or muscle oxygenation parameters compared to PL in resistance-trained men.


Assuntos
Citrullus , Treinamento Resistido , Teorema de Bayes , Citrulina , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Masculino , Força Muscular , Músculo Esquelético/fisiologia
7.
J Therm Biol ; 105: 103227, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35393039

RESUMO

L-Citrulline is a non-protein amino acid that promotes arginine recycling and muscle protein synthesis. This study investigated whether L-citrulline can exert these functions in heat-stressed chickens. Arbor acre broilers were fed either basal diets (Control) or basal diets supplemented with 1% L-citrulline (L-Cit). At 28 d old, broilers were subjected to two environmental temperatures, 35 °C for 8 h/d (HS) or 24 °C for 24 h/d (TNZ) for 2 weeks. The experiment was designed as a 2 by 2 factorial arrangement. Results showed that HS increased the core body temperature (CBT) and rectal temperature of broilers compared to the TNZ condition. The CBT and mean CBT decreased by ∼0.5oC in TNZ + L-Cit broilers compared to the TNZ + Control group (P < 0.05). L-Cit supplementation at TNZ significantly (P < 0.05) lowered the plasma malondialdehyde content but this was increased during HS. Exposure to HS significantly (P < 0.05) elevated plasma malondialdehyde compared to TNZ condition. Plasma immunoglobulin A, G, and M were increased (P < 0.05) by TNZ + L-Cit compared to the TNZ + Control group. Plasma nitric oxide and endothelial nitric oxide synthase (NOS) activity was increased during HS, whereas the total and inducible NOS enzymes were decreased. In addition, L-Cit supplementation increased both the inducible and endothelial NOS isoforms (P < 0.05). The mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1-α, avian uncoupling protein, cytochrome C oxidase subunit 3, and ATP synthase F1 subunit beta (ATP5ß) in the breast muscle were downregulated (P < 0.05) during HS. However, L-Cit supplementation upregulated the mitochondrial transcription factor A and during HS, L-Cit increased ATP5ß expression similar to TNZ housed broilers. Therefore, this study demonstrates that dietary L-Cit can lower the body temperature, decrease lipid peroxidation and promote the immune status of broilers under thermoneutrality. Also, L-Cit would act to promote muscle ATP generation during heat stress in broilers.


Assuntos
Galinhas , Transtornos de Estresse por Calor , Trifosfato de Adenosina/metabolismo , Animais , Galinhas/fisiologia , Citrulina/metabolismo , Citrulina/farmacologia , Suplementos Nutricionais , Transtornos de Estresse por Calor/metabolismo , Resposta ao Choque Térmico , Imunidade , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo
8.
J Vector Borne Dis ; 59(1): 45-51, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35708403

RESUMO

BACKGROUND & OBJECTIVES: Malaria affects around 228 million people all over the globe. Malaria causing parasite Plasmodium infection leads to activation of immune responses. The growth of parasite and immune activation requires semi essential amino acids like L-arginine. Malaria infection leads to condition of hyperargininemia and low availability of nitric oxide. However, the effect of L-arginine supplementation in malaria infected mice has not been explored in in-vivo studies. In this study we have compared the effect of oral supplementation of nitric oxide donor, L-arginine and L-citrulline, in malaria infected mice Methods: To examine the effect of oral supplementation of L-arginine and L-citrulline, Plasmodium berghei infected mice were divided in different groups and respective groups were fed with L- arginine and L-citrulline, parasitemia was measured on different days. Mice was sacrificed and immunophenotyping was done on 10 days post infection. RESULTS: our results show that supplementation of L-arginine induces conducive environment for Plasmodium growth due to which the infected mice dies earlier than control wild type infected mice whereas L-citrulline supplementation inhibits parasite growth and mice survives for longer period of time. Flow cytometric analysis shows that supplementation of L-arginine increases cTLA-4 on T cell population, increases Treg cells leading to immunosuppression while supplementation of L-citrulline does not have effect on T cells population and number of Treg cell decrease compared to P. berghei infected mice. INTERPRETATION & CONCLUSION: our results show that L-citrulline can be a better alternative than L-arginine because of lower expression of inhibitory molecules and lower parasitemia as well as increased survival of infected mice.


Assuntos
Citrulina , Malária , Animais , Arginina/metabolismo , Arginina/farmacologia , Citrulina/metabolismo , Citrulina/farmacologia , Humanos , Malária/prevenção & controle , Camundongos , Parasitemia/prevenção & controle , Plasmodium berghei , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia
9.
Metab Eng ; 68: 220-231, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34688880

RESUMO

L-citrulline is a high-value amino acid with promising application in medicinal and food industries. Construction of highly efficient microbial cell factories for L-citrulline production is still an open issue due to complex metabolic flux distribution and L-arginine auxotrophy. In this study, we constructed a nonauxotrophic cell factory in Escherichia coli for high-titer L-citrulline production by coupling modular engineering strategies with dynamic pathway regulation. First, the biosynthetic pathway of L-citrulline was enhanced after blockage of the degradation pathway and introduction of heterologous biosynthetic genes from Corynebacterium glutamicum. Specifically, a superior recycling biosynthetic pathway was designed to replace the native linear pathway by deleting native acetylornithine deacetylase. Next, the carbamoyl phosphate and L-glutamate biosynthetic modules, the NADPH generation module, and the efflux module were modified to increase L-citrulline titer further. Finally, a toggle switch that responded to cell density was designed to dynamically control the expression of the argG gene and reconstruct a nonauxotrophic pathway. Without extra supplement of L-arginine during fermentation, the final CIT24 strain produced 82.1 g/L L-citrulline in a 5-L bioreactor with a yield of 0.34 g/g glucose and a productivity of 1.71 g/(L ⋅ h), which were the highest values reported by microbial fermentation. Our study not only demonstrated the successful design of cell factory for high-level L-citrulline production but also provided references of coupling the rational module engineering strategies and dynamic regulation strategies to produce high-value intermediate metabolites.


Assuntos
Vias Biossintéticas , Corynebacterium glutamicum , Vias Biossintéticas/genética , Citrulina/metabolismo , Corynebacterium glutamicum/genética , Corynebacterium glutamicum/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Fermentação , Engenharia Metabólica
10.
Br J Nutr ; : 1-23, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34134794

RESUMO

L-citrulline (L-Cit) is a nonessential amino acid that stimulates nitric oxide (NO) production and improves exercise performance by reducing muscle damage indices; however, the direct benefits of L-Cit on antioxidant markers are unclear. The aim of this study was to examine antioxidant responses to high-intensity interval exercise following acute L-Cit supplementation. Nine young men (21 ± 1 years) participated in a double-blind crossover study in which they received 12 g of L-Cit and placebo (PL) an hour prior to high-intensity interval exercise on two occasions, separated by a seven-day washout period. Blood samples were obtained before (PRE), immediately after (IP), 10 (10P), and 30 min after exercise (30P) from the cubital vein using standard procedures. Serum concentrations of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and NO metabolites (NOx) were measured. The exercise protocol significantly elevated SOD (p = 0.01) and GPx (p = 0.048) from PRE to 10P in the L-Cit group with greater changes than the PL group. CAT concentrations increased IP (p = 0.014) and remained elevated at 10P (p = 0.03) and 30P (p = 0.015) in both the L-Cit and PL conditions. NOx concentrations increased IP (p = 0.05) in the L-Cit group with greater changes than PL group in PRE to IP, PRE to 10P, and PRE to 30P (p < 0.05). Our data indicate that L-Cit supplementation (single 12 g dose pre-exercise) induces improvements in antioxidant markers following a session of high-intensity interval exercise in young men.

11.
Br J Nutr ; : 1-34, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34863321

RESUMO

L-citrulline may improve non-invasive vascular function and cardiometabolic risk markers through increases in L-arginine bioavailability and nitric oxide synthesis. A meta-analysis of randomized controlled trials (RCTs) was performed to examine longer-term and postprandial effects of L-citrulline supplementation and watermelon consumption on these markers for cardiovascular disease in adults. Summary estimates of weighted mean differences (WMDs) in vascular function and cardiometabolic risk markers with accompanying 95% confidence intervals (CIs) were calculated using random or fixed-effect meta-analyses. Seventeen RCTs were included involving an L-citrulline intervention, of which six studied postprandial and twelve longer-term effects. Five studies investigated longer-term effects of watermelon consumption and five assessed effects during the postprandial phase. Longer-term L-citrulline supplementation improved brachial artery flow-mediated vasodilation (FMD) by 0.9 %-point (95 % CI: 0.7 to 1.1, P < 0.001). Longer-term watermelon consumption improved pulse wave velocity by 0.9 m/s (95% CI: 0.1 to 1.5, P < 0.001), while effects on FMD were not studied. No postprandial effects on vascular function markers were found. Postprandial glucose concentrations decreased by 0.6 mmol/L (95% CI: 0.4 to 0.7, P < 0.001) following watermelon consumption, but no other longer-term or postprandial effects were observed on cardiometabolic risk markers. To conclude, longer-term L-citrulline supplementation and watermelon consumption may improve vascular function, suggesting a potential mechanism by which increased L-citrulline intake beneficially affects cardiovascular health outcomes in adults. No effects on postprandial vascular function markers were found, while more research is needed to investigate effects of L-citrulline and watermelon on risk markers related to cardiometabolic health.

12.
Phytother Res ; 35(6): 3157-3166, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33876875

RESUMO

This study investigated the impact of L-citrulline on glucose homeostasis, lipid profile, and inflammatory factors in overweight and obese patients with type 2 diabetes (T2D). In total, 54 participants with T2D were assigned to L-citrulline (3 g/day L-citrulline) or placebo groups and tested for 8 weeks. Serum levels of insulin, fasting glucose, hemoglobin A1c (HbA1c), lipid profile, tumor necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), and L-citrulline were measured pre- and post-intervention. Totally, 45 patients were enrolled in the research. L-citrulline supplementation decreased serum levels of insulin (p = .025), glucose (p = .032), HbA1c (p = .001), HOMA-IR (p = .037), TNF-α (p = .036), and hs-CRP (p = .027) significantly. At the end of the study, despite the significant decrease in serum levels of triglyceride (p = .027) and the increase in high-density lipoprotein cholesterol levels (p < .001) in the L-citrulline group, no significant differences were found for these parameters between the groups. Moreover, no significant inter- and intra-group changes were observed for dietary intakes, anthropometric indices, total and low-density lipoprotein cholesterol levels (p > .05). In conclusion, L-citrulline supplementation might improve glucose homeostasis, some lipid factors and inflammatory markers in overweight and obese patients with T2D.


Assuntos
Citrulina/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Obesidade/tratamento farmacológico , Sobrepeso/tratamento farmacológico , Adulto , Glicemia/metabolismo , Proteína C-Reativa/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , Jejum , Feminino , Hemoglobinas Glicadas/metabolismo , Homeostase , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
13.
Int J Sport Nutr Exerc Metab ; 31(4): 350-358, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34010809

RESUMO

Citrulline malate (CitMal) is a dietary supplement that is suggested to enhance strength training performance. However, there is conflicting evidence on this matter. Thus, the purpose of this meta-analysis was to determine whether supplementing with CitMal prior to strength training could increase the total number of repetitions performed before reaching voluntary muscular failure. A systematic search was conducted wherein the inclusion criteria were double-blind, placebo-controlled studies in healthy participants that examined the effect of CitMal on repetitions to failure during upper body and lower body resistance exercises. The Hedges's g standardized mean differences (SMD) between the placebo and CitMal trials were calculated and used in a random effect model. Two separate subanalyses were performed for upper body and lower body exercises. Eight studies, including 137 participants who consisted of strength-trained men (n = 101) and women (n = 26) in addition to untrained men (n = 9), fulfilled the inclusion criteria. Across the studies, 14 single-joint and multijoint exercises were performed with an average of 51 ± 23 total repetitions during 5 ± 3 sets per exercise at ∼70% of one-repetition maximum. Supplementing with 6-8 g of CitMal 40-60 min before exercise increased repetitions by 3 ± 5 (6.4 ± 7.9%) compared with placebo (p = .022) with a small SMD (0.196). The subanalysis for the lower body resulted in a tendency for an effect of the supplement (8.1 ± 8.4%, SMD: 0.27, p = .051) with no significant effect for the upper body (5.7 ± 8.4%, SMD: 0.16, p = .131). The current analysis observed a small ergogenic effect of CitMal compared with placebo. Acute CitMal supplementation may, therefore, delay fatigue and enhance muscle endurance during high-intensity strength training.


Assuntos
Citrulina/análogos & derivados , Malatos/farmacologia , Substâncias para Melhoria do Desempenho/farmacologia , Resistência Física/efeitos dos fármacos , Desempenho Físico Funcional , Treinamento Resistido/métodos , Adulto , Viés , Citrulina/administração & dosagem , Citrulina/farmacologia , Método Duplo-Cego , Feminino , Humanos , Malatos/administração & dosagem , Masculino , Resistência Física/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Adulto Jovem
14.
J Food Sci Technol ; 58(12): 4730-4737, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34629537

RESUMO

The aim the current study was to developed a watermelon rind powder (WRP), watermelon pulp powder (WPP), and beetroot powder (BP), in order to compare the stability of L-citrulline and nitrate with that of watermelon rind juice (WRJ), watermelon pulp juice (WPJ), and beetroot juice (BJ), respectively. The stability was evaluated during 32 days at 25, 4 and - 20 ºC. L-arginine and L-ornithine content were also evaluated. At day 0, a significantly higher L-citrulline and L-ornithine content in WRP was observed when compared to WPP. However, a significantly lower L-arginine content in WRP was observed when compared to WPP. L-citrulline content in WRP and WRJ was stable over 32 days in all temperatures evaluated, whereas it reduced in WPP in 32 days at 25 ºC and it is reduced in in WPJ in day 16 and day 32 at 25 °C. L-arginine content in WRP and WPP was stable over 32 days in all temperatures evaluated. A reduction was observed in WRJ at day 2, 4 and 32 at 25 °C and in WPJ at day 2, 4, 8, 16 and 32 days at 25 °C. L-ornithine content in WRP and WPP was stable over 32 days in all temperatures evaluated. An increase was observed in WRJ at day 2, 4 and 32 at 25 °C and in WPJ in day 2, 4, 8, 16 and 32 at 25 °C. Nitrate content in BP was stable over 32 days in all temperatures evaluated, while nitrate content in beetroot juice was reduced in day 2 at 25 °C and day 8 at 4 °C. In conclusion, L-citrulline of the microencapsulated watermelon rind and nitrate of the microencapsulated beetroot were stable throughout storage.

15.
Am J Physiol Gastrointest Liver Physiol ; 318(5): G912-G927, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32174131

RESUMO

Glucagon regulates the hepatic amino acid metabolism and increases ureagenesis. Ureagenesis is activated by N-acetylglutamate (NAG), formed via activation of N-acetylglutamate synthase (NAGS). With the aim to identify the steps whereby glucagon both acutely and chronically regulates ureagenesis, we investigated whether glucagon receptor-mediated activation of ureagenesis is required in a situation where NAGS activity and/or NAG levels are sufficient to activate the first step of the urea cycle in vivo. Female C57BL/6JRj mice treated with a glucagon receptor antagonist (GRA), glucagon receptor knockout (Gcgr-/-) mice, and wild-type (Gcgr+/+) littermates received an intraperitoneal injection of N-carbamoyl glutamate (Car; a stable variant of NAG), l-citrulline (Cit), Car and Cit (Car + Cit), or PBS. In separate experiments, Gcgr-/- and Gcgr+/+ mice were administered N-carbamoyl glutamate and l-citrulline (wCar + wCit) in the drinking water for 8 wk. Car, Cit, and Car + Cit significantly (P < 0.05) increased plasma urea concentrations, independently of pharmacological and genetic disruption of glucagon receptor signaling (P = 0.9). Car increased blood glucose concentrations equally in GRA- and vehicle-treated mice (P = 0.9), whereas the increase upon Car + Cit was impaired in GRA-treated mice (P = 0.008). Blood glucose concentrations remained unchanged in Gcgr-/- mice upon Car (P = 0.2) and Car + Cit (P = 0.9). Eight weeks administration of wCar + wCit did not change blood glucose (P > 0.2), plasma amino acid (P > 0.4), and urea concentrations (P > 0.3) or the area of glucagon-positive cells (P > 0.3) in Gcgr-/- and Gcgr+/+ mice. Our data suggest that glucagon-mediated activation of ureagenesis is not required when NAGS activity and/or NAG levels are sufficient to activate the first step of the urea cycle.NEW & NOTEWORTHY Hepatic ureagenesis is essential in amino acid metabolism and is importantly regulated by glucagon, but the exact mechanism is unclear. With the aim to identify the steps whereby glucagon both acutely and chronically regulates ureagenesis, we here show, contrary to our hypothesis, that glucagon receptor-mediated activation of ureagenesis is not required when N-acetylglutamate synthase activity and/or N-acetylglutamate levels are sufficient to activate the first step of the urea cycle in vivo.


Assuntos
Citrulina/administração & dosagem , Glucagon/metabolismo , Glutamatos/administração & dosagem , Fígado/efeitos dos fármacos , Receptores de Glucagon/deficiência , Receptores de Glucagon/metabolismo , Ureia/sangue , Aminoácido N-Acetiltransferase/metabolismo , Animais , Carbamoil-Fosfato Sintase (Amônia)/metabolismo , Feminino , Glutamatos/metabolismo , Antagonistas de Hormônios/administração & dosagem , Fígado/enzimologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Glucagon/antagonistas & inibidores , Receptores de Glucagon/genética
16.
Exp Physiol ; 105(2): 270-281, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31802553

RESUMO

NEW FINDINGS: What is the central question of the study? Does the action of l-citrulline, which has been shown to augment performance in animals and athletes, possibly via increasing mitochondrial function, translate to obese animals, and does this improve glycaemia? What is the main finding and its importance? Chronic supplementation with l-citrulline improves not only exercise capacity, but also glycaemia in obese mice, which would be beneficial as obese individuals are at increased risk for type 2 diabetes. However, l-citrulline supplementation also caused a mild impairment in insulin signalling and insulin tolerance in obese mice. ABSTRACT: l-Citrulline is an organic α-amino acid that has been shown to have a number of salutary actions on whole-body physiology, including reducing muscle wasting and augmenting exercise and muscle performance. The latter has been suggested to arise from elevations in mitochondrial function. Because enhancing mitochondrial function has been proposed as a novel strategy to mitigate insulin resistance, our goal was to determine whether supplementation with l-citrulline could also improve glycaemia in an experimental mouse model of obesity. We hypothesized that l-citrulline treatment would improve glycaemia in obese mice, and this would be associated with elevations in skeletal muscle mitochondrial function. Ten-week-old C57BL/6J mice were fed either a low-fat (10% kcal from lard) or a high-fat (60% kcal from lard) diet, while receiving drinking water supplemented with either vehicle or l-citrulline (0.6 g l-1 ) for 15 weeks. Glucose homeostasis was assessed via glucose/insulin tolerance testing, while in vivo metabolism was assessed via indirect calorimetry, and forced exercise treadmill testing was utilized to assess endurance. As expected, obese mice supplemented with l-citrulline exhibited an increase in exercise capacity, which was associated with an improvement in glucose tolerance. Consistent with augmented mitochondrial function, we observed an increase in whole body oxygen consumption rates in obese mice supplemented with l-citrulline. Surprisingly, l-citrulline supplementation worsened insulin tolerance and reduced insulin signalling in obese mice. Taken together, although l-citrulline supplementation improves both glucose tolerance and exercise capacity in obese mice, caution must be applied with its broad use as a nutraceutical due to a potential deterioration of insulin sensitivity.


Assuntos
Glicemia/efeitos dos fármacos , Citrulina/farmacologia , Tolerância ao Exercício/efeitos dos fármacos , Obesidade/tratamento farmacológico , Animais , Glicemia/metabolismo , Citrulina/uso terapêutico , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Tolerância ao Exercício/fisiologia , Resistência à Insulina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Fibras Musculares Esqueléticas/efeitos dos fármacos , Fibras Musculares Esqueléticas/metabolismo , Obesidade/metabolismo
17.
Int J Food Sci Nutr ; 71(4): 482-489, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31597484

RESUMO

The objective of this study was to determine the effects of a single pre-exercise dose of watermelon juice on submaximal post-exercise heart rate (HR) recovery, blood lactate (BL), blood pressure (BP), blood glucose (BG), and muscle soreness in healthy adults. In a randomised crossover design, 27 healthy non-athletic participants (13 males/14 females) consumed 355 mL of watermelon juice, Gatorade, sugar water, or water. HR and BL were significantly higher post-exercise, and both watermelon juice and sugar water increased postprandial BG. However, there were no significant differences among the supplements in HR recovery, BL, or post-exercise muscle soreness. Watermelon juice prevented increased post-exercise systolic and diastolic BP in females, but not in males. More research is warranted to examine the effect of sex on the efficacy of watermelon consumption for controlling BP.


Assuntos
Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Citrullus , Suplementos Nutricionais , Sucos de Frutas e Vegetais , Frequência Cardíaca/efeitos dos fármacos , Lactatos/sangue , Mialgia/tratamento farmacológico , Adulto , Citrulina/farmacologia , Exercício Físico , Feminino , Humanos , Masculino , Extratos Vegetais/administração & dosagem , Adulto Jovem
18.
Int J Mol Sci ; 21(5)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32121248

RESUMO

L-arginine/nitric oxide pathway in Crohn's disease (CD) and ulcerative colitis (UC) is poorly investigated. The aim of current study is to quantify pathway serum metabolites in 52 CD (40 active), 48 UC (33 active), and 18 irritable bowel syndrome patients and 40 controls using mass spectrometry and at determining mRNA expression of pathway-associated enzymes in 91 bowel samples. Arginine and symmetric dimethylarginine decreased (p < 0.05) in active-CD (129 and 0.437 µM) compared to controls (157 and 0.494 µM) and active-UC (164 and 0.52 µM). Citrulline and dimethylamine increased (p < 0.05) in active-CD (68.7 and 70.9 µM) and active-UC (65.9 and 73.9 µM) compared to controls (42.7 and 50.4 µM). Compared to normal, CD-inflamed small bowel had downregulated (p < 0.05) arginase-2 by 2.4-fold and upregulated dimethylarginine dimethylaminohydrolase (DDAH)-2 (1.5-fold) and arginine N-methyltransferase (PRMT)-2 (1.6-fold). Quiescent-CD small bowel had upregulated (p < 0.05) arginase-2 (1.8-fold), DDAH1 (2.9-fold), DDAH2 (1.5-fold), PRMT1 (1.5-fold), PRMT2 (1.7-fold), and PRMT5 (1.4-fold). Pathway enzymes were upregulated in CD-inflamed/quiescent and UC-inflamed colon as compared to normal. Compared to inflamed, quiescent CD-colon had upregulated DDAH1 (5.7-fold) and ornithine decarboxylase (1.6-fold). Concluding, the pathway is deregulated in CD and UC, also in quiescent bowel, reflecting inflammation severity and angiogenic potential. Functional analysis of PRMTs and DDAHs as potential targets for therapy is warranted.


Assuntos
Arginina/metabolismo , Inflamação/genética , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Metabolômica , Neovascularização Fisiológica , Óxido Nítrico/metabolismo , Transcrição Gênica , Adulto , Apoptose/genética , Proliferação de Células/genética , Endoscopia , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/patologia , Intestinos/patologia , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/metabolismo , Síndrome do Intestino Irritável/patologia , Masculino , Metaboloma/genética , Neovascularização Fisiológica/genética , Fenótipo
19.
Molecules ; 25(22)2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33187365

RESUMO

Watermelon (Citrulus lantus) is an important horticultural crop which belongs to the Curcubitaceae family. The nutraceutical potential of watermelon has been illustrated by several researchers, which makes it a better choice of functional food. Watermelon has been used to treat various ailments, such as cardio-vascular diseases, aging related ailments, obesity, diabetes, ulcers, and various types of cancers. The medicinal properties of watermelon are attributed by the presence of important phytochemicals with pharmaceutical values such as lycopene, citrulline, and other polyphenolic compounds. Watermelon acts as vital source of l-citrulline, a neutral-alpha amino acid which is the precursor of l-arginine, an essential amino acid necessary for protein synthesis. Supplementation of l-citrulline and lycopene displayed numerous health benefits in in vitro and in vivo studies. Similarly, the dietary intake of watermelon has proven benefits as functional food in humans for weight management. Apart from the fruits, the extracts prepared from the seeds, sprouts, and leaves also evidenced medicinal properties. The present review provides a comprehensive overview of benefits of watermelon for the treatment of various ailments.


Assuntos
Citrullus/química , Suplementos Nutricionais , Compostos Fitoquímicos/química , Extratos Vegetais/farmacologia , Aminoácidos/química , Animais , Antioxidantes/química , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Citrulina/química , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/prevenção & controle , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/prevenção & controle , Dieta , Frutas/química , Alimento Funcional , Horticultura , Humanos , Licopeno/química , Óxido Nítrico/metabolismo , Obesidade/tratamento farmacológico , Obesidade/prevenção & controle , Plantas Medicinais/metabolismo
20.
Biochem Biophys Res Commun ; 512(4): 712-715, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-30926170

RESUMO

l-Ornithine is found in animals as a free amino acid and is a vital component of the urea cycle in the liver; it is reported to have various functions such as promoting wound healing, promoting growth hormone secretion, hypnotic effects, and so on. The present study aimed to investigate the effects of a single oral administration of l-ornithine on 1) the metabolism of amino acids in the liver and skin of mice and 2) the metabolism of polyamines in the skin of mice. To this end, ICR mice were separated into five groups; four groups were administered l-ornithine dissolved in fresh water (3.0 mmol/10 ml/kg) and a fifth group, the control, was not administered l-ornithine. The four groups comprised mice sampled at specific times (30, 60, 120 and 180 min) after oral administration of l-ornithine. We found that metabolism of l-ornithine to l-citrulline was rapid and that l-citrulline concentration remained high in mice sampled at later stages. Similarly, the concentrations of l-proline and glycine, both of which are important components of collagen, also rapidly increased in the skin following l-ornithine treatment. The concentrations of polyamines (putrescine, spermidine and spermine), which are known to increase the synthesis of certain proteins and enhance the epidermal barrier function, were also significantly increased in the skin. Our study shows that oral administration of l-ornithine significantly influences the chemical composition of the skin of mice through increases in both amino acids and polyamines after a short period of time.


Assuntos
Aminoácidos/metabolismo , Colágeno/metabolismo , Ornitina/metabolismo , Poliaminas/metabolismo , Pele/metabolismo , Administração Oral , Animais , Masculino , Camundongos Endogâmicos ICR , Ornitina/administração & dosagem , Putrescina/metabolismo , Espermidina/metabolismo , Espermina/metabolismo
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