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Sample records for l-arginine supplementation differentially

  1. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males.

    PubMed

    Suzuki, Takashi; Morita, Masahiko; Hayashi, Toshio; Kamimura, Ayako

    2017-02-01

    We investigated the effects of combining 1 g of l-citrulline and 1 g of l-arginine as oral supplementation on plasma l-arginine levels in healthy males. Oral l-citrulline plus l-arginine supplementation more efficiently increased plasma l-arginine levels than 2 g of l-citrulline or l-arginine, suggesting that oral l-citrulline and l-arginine increase plasma l-arginine levels more effectively in humans when combined.

  2. L-arginine as dietary supplement for improving microvascular function.

    PubMed

    Melik, Ziva; Zaletel, Polona; Virtic, Tina; Cankar, Ksenija

    2017-01-01

    Reduced availability of nitric oxide leads to dysfunction of endothelium which plays an important role in the development of cardiovascular diseases. The aim of the present study was to determine whether the dietary supplement L-arginine improves the endothelial function of microvessels by increasing nitric oxide production. We undertook experiments on 51 healthy male volunteers, divided into 4 groups based on their age and physical activity since regular physical activity itself increases endothelium-dependent vasodilation. The skin laser Doppler flux was measured in the microvessels before and after the ingestion of L-arginine (0.9 g). The endothelium-dependent vasodilation was assessed by acetylcholine iontophoresis and the endothelium-independent vasodilation by sodium nitroprusside iontophoresis. In addition, we measured endothelium-dependent and endothelium-independent vasodilation in 81 healthy subjects divided into four age groups. After the ingestion of L-arginine, the endothelium-dependent vasodilation in the young trained subjects increased (paired t-test, p < 0.05), while in the other groups it remained the same. There were no differences in the endothelium-independent vasodilation after ingestion of L-arginine. With aging endothelium-independent vasodilation decreased while endothelium-dependent vasodilation remained mainly unchanged. Obtained results demonstrated that a single dose of L-arginine influences endothelium-dependent vasodilation predominantly in young, trained individuals.

  3. Safety of long-term dietary supplementation with L-arginine in pigs.

    PubMed

    Hu, Shengdi; Li, Xilong; Rezaei, Reza; Meininger, Cynthia J; McNeal, Catherine J; Wu, Guoyao

    2015-05-01

    This study was conducted with a swine model to determine the safety of long-term dietary supplementation with L-arginine-HCl or L-arginine free base. Beginning at 30 days of age, pigs were fed a corn- and soybean meal-based diet (31.5 g/kg body weight/day) supplemented with 0, 1.21, 1.81 or 2.42 % L-arginine-HCl (Experiment 1) or with 0, 1, 1.5 or 2 % L-arginine (Experiment 2). The supplemental doses of 0, 1, 1.5, and 2 % L-arginine provided pigs with 0, 315, 473, and 630 mg L-arginine/kg body weight/day, respectively, which were equivalent to 0, 286, 430, and 573 mg L-arginine/kg body weight/day, respectively, in humans. At 121 days of age (91 days after initiation of supplementation), blood samples were obtained from the jugular vein of pigs at 1 and 4 h after feeding for hematological and clinical chemistry tests. Dietary supplementation with L-arginine increased plasma concentrations of arginine, ornithine, proline, albumin and reticulocytes, while reducing plasma concentrations of ammonia, free fatty acids, triglyceride, cholesterol, and neutrophils. L-Arginine supplementation enhanced protein gain and reduced white-fat deposition in the body. Other variables in standard hematology and clinical chemistry tests, serum concentrations of insulin, growth hormone and insulin-like growth factor-I did not differ among all the groups of pigs. These results indicate that dietary supplementation with L-arginine (up to 630 mg/kg body weight/day) is safe in pigs for at least 91 days. Our findings help guide clinical studies to determine the safety of long-term oral administration of L-arginine to humans.

  4. Effects of a chronic l-arginine supplementation on the arginase pathway in aged rats.

    PubMed

    Moretto, Johnny; Guglielmetti, Anne-Sophie; Tournier-Nappey, Maude; Martin, Hélène; Prigent-Tessier, Anne; Marie, Christine; Demougeot, Céline

    2017-04-01

    While ageing is frequently associated with l-arginine deficiency, clinical and experimental studies provided controversial data on the interest of a chronic l-arginine supplementation with beneficial, no or even deleterious effects. It was hypothesized that these discrepancies might relate to a deviation of l-arginine metabolism towards production of l-ornithine rather than nitric oxide as a result of age-induced increase in arginase activity. This study investigated the effect of ageing on arginase activity/expression in target tissues and determined whether l-arginine supplementation modulated the effect of ageing on arginase activity. Arginase activity and expression were measured in the heart, vessel, brain, lung, kidney and liver in young rats (3-months old) and aged Wistar rats (22-24-months-old) with or without l-arginine supplementation (2.25% in drinking water for 6weeks). Plasma levels of l-arginine and l-ornithine were quantified in order to calculate the plasma l-arginine/l-ornithine ratio, considered as a reflection of arginase activity. Cardiovascular parameters (blood pressure, heart rate) and aortic vascular reactivity were also studied. Ageing dramatically reduced plasma l-arginine and l-arginine/l-ornithine ratio, decreased liver and kidney arginase activities but did not change activities in other tissues. l-Arginine supplementation normalized plasma l-arginine and l-arginine/l-ornithine ratio, improved endothelial function and decreased systolic blood pressure. These effects were associated with decreased arginase activity in aorta along with no change in the other tissues except in the lung in which activity was increased. A strong mismatch was therefore observed between arginase activity and expression in analyzed tissues. The present study reveals that ageing selectively changes arginase activity in clearance tissues, but does not support a role of the arginase pathway in the potential deleterious effect of the l-arginine supplementation in

  5. L-Arginine supplementation improves antioxidant defenses through L-arginine/nitric oxide pathways in exercised rats.

    PubMed

    Shan, Lingling; Wang, Bin; Gao, Guizhen; Cao, Wengen; Zhang, Yunkun

    2013-10-15

    l-Arginine (l-Arg) supplementation has been shown to enhance physical exercise capacity and delay onset of fatigue. This work investigated the potential beneficial mechanism(s) of l-Arg supplementation by examining its effect on the cellular oxidative and nitrosative stress pathways in the exercised rats. Forty-eight rats were randomly divided into six groups: sedentary control; sedentary control with l-Arg treatment; endurance training (daily swimming training for 8 wk) control; endurance training with l-Arg treatment; an exhaustive exercise (one time swimming to fatigue) control; and an exhaustive exercise with l-Arg treatment. l-Arg (500 mg/kg body wt) or saline was given to rats by intragastric administration 1 h before the endurance training and the exhaustive swimming test. Expression levels and activities of the l-Arg/nitric oxide (NO) pathway components and parameters of the oxidative stress and antioxidant defense capacity were investigated in l-Arg-treated and control rats. The result show that the l-Arg supplementation completely reversed the exercise-induced activation of NO synthase and superoxide dismutase, increased l-Arg transport capacity, and increased NO and anti-superoxide anion levels. These data demonstrate that l-Arg supplementation effectively reduces the exercise-induced imbalance between oxidative stress and antioxidant defense capacity, and this modulation is likely mediated through the l-Arg/NO pathways. The findings of this study improved our understanding of how l-Arg supplementation prevents elevations of reactive oxygen species and favorably enhances the antioxidant defense capacity during physical exercise.

  6. L-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats.

    PubMed

    de Aguiar Picanço, Etiene; Lopes-Paulo, Francisco; Marques, Ruy G; Diestel, Cristina F; Caetano, Carlos Eduardo R; de Souza, Mônica Vieira Mano; Moscoso, Gabriela Mendes; Pazos, Helena Maria F

    2011-05-01

    Radiotherapy is widely used for cancer treatment but has harmful effects. This study aimed to assess the effects of L-arginine and glycine supplementation on the colon wall of rats submitted to abdominal irradiation. Forty male Wistar rats were randomly divided into four groups: I-healthy, II-irradiated with no amino acid supplementation, III-irradiated and supplemented with L-arginine, and IV-irradiated and supplemented with glycine. The animals received supplementation for 14 days, with irradiation being applied on the eighth day of the experiment. All animals underwent laparotomy on the 15th day for resection of a colonic segment for stereologic analysis. Parametric and nonparametric tests were used for statistical analysis, with the level of significance set at p ≤0.05. Stereologic analysis showed that irradiation induced a reduction of the total volume of the colon wall of group II and III animals compared to healthy controls, but not of group IV animals supplemented with glycine. The mucosal layer of the irradiated animals of all groups was reduced compared to healthy group I animals, but supplementation with L-arginine and glycine was effective in maintaining the epithelial surface of the mucosal layer. The present results suggest that glycine supplementation had a superior effect on the irradiated colon wall compared to L-arginine supplementation since it was able to maintain the thickness of the wall and the epithelial surface of the mucosa, whereas L-arginine maintained the partial volume of the epithelium and the epithelial surface, but not the total volume of the intestinal wall.

  7. Ameliorated effect of L-arginine supplementation on gingival morphology in cyclosporin-treated rats.

    PubMed

    Fu, E; Tz-Chong, C; Liu, D; Chiu, S C

    2000-11-01

    The role of nitric oxide (NO) in the pathogenesis of cyclosporin (CsA)-induced gingival overgrowth is unknown. The purpose of the present study was to evaluate the effect of NO substrate (L-arginine) and blockade (N-nitro-L-arginine methylester-hydrochloride, L-NAME) on the gingival morphology in CsA-fed rats. Sixty CsA-fed (10 mg/kg/day) male Sprague-Dawley rats were assigned to 3 groups. Animals in 2 experimental groups received L-arginine (1% weight/weight) in rat chowder or L-NAME (50 mg/l) in drinking water, respectively, for 4 weeks. Rats in the control group were fed a normal diet and water. At week 0, 2, and 4, dental stone models were made from the mandibular anterior region and the gingival dimensions (width, depth, and height) were measured. The tail cuff blood pressure and the plasma nitrate level were also measured at week 4 to monitor the effects of L-arginine and L-NAME treatment. No significant difference in the gingival dimensions was noticed at week 0; however, significant differences were observed at weeks 2 and 4, except the buccolingual depth at week 2. While the magnitude of gingival dimensions was large, moderate, and small in control, L-NAME, and L-arginine groups, respectively, we found significantly reduced gingival dimensions in both L-arginine supplement and L-NAME groups. Nevertheless, the reduced gingival overgrowth in the L-NAME treatment group was far less than that in the exogenous NO treatment group. Plasma NO2-/NO3- concentrations were also significantly different; i.e., from the highest to the lowest levels were the L-arginine, CsA control, and L-NAME group, respectively. A significantly increased mean and diastolic blood pressure was found in the L-NAME group compared to the L-arginine group. Gingival morphology in CsA-fed rats was evaluated after NO substrate (L-arginine) and blockade (L-NAME) treatment for 4 weeks. Significantly decreased dimensions were noted in the L-arginine group compared to the CsA group at weeks 2 and 4

  8. Supplementation with rumen-protected L-arginine-HCl increased fertility in sheep with synchronized estrus.

    PubMed

    de Chávez, Julio Agustín Ruiz; Guzmán, Adrian; Zamora-Gutiérrez, Diana; Mendoza, Germán David; Melgoza, Luz María; Montes, Sergio; Rosales-Torres, Ana María

    2015-08-01

    The aim of the present study was to evaluate the effects of L-arginine-HCl supplementation on ovulation rate, fertility, prolificacy, and serum VEGF concentrations in ewes with synchronized oestrus. Thirty Suffolk ewes with a mean body weight of 45 ± 3 kg and a mean body condition score (BCS) of 2.4 ± 0.28 were synchronized for estrus presentation with a progestin-containing sponge (20 mg Chronogest® CR) for 9 days plus PGF2-α (Lutalyse; Pfizer, USA) on day 7 after the insertion of the sponge. The ewes were divided into two groups; i.e., a control group (n = 15) that was fed on the native pasture (basal diet) and an L-arginine-HCl group (n = 15) that received 7.8 g of rumen-protected L-arginine-HCl from day 5 of the sponge insertion until day 25 after mating plus the basal diet. The L-arginine-HCl was administered daily via an esophageal probe between days 5 and 9 of the synchronization protocol and every third day subsequently. Blood samples were drawn from the jugular vein every 6 days throughout the entire experimental period. The results revealed that the L-arginine-HCl supplementation increased fertility during the synchronized estrus (P = 0.05). However, no effects were observed on the final BCS (P = 0.78), estrus presentation (P = 0.33), multiple ovulations (P = 0.24), prolificacy (P = 0.63), or serum VEGF concentration. In conclusion, L-arginine-HCl supplementation during the period used in this study increased fertility in sheep with synchronized estrus possibly due to improved embryo-fetal survival during early pregnancy.

  9. Dietary L-arginine supplementation attenuates lipopolysaccharide-induced inflammatory response in broiler chickens

    USDA-ARS?s Scientific Manuscript database

    Two experiments were conducted to investigate the effect of dietary L-arginine (Arg) supplementation on inflammatory response and innate immunity of broilers. Experiment 1 was designed as a 2 × 3 factorial arrangement (n = 8 cages/treatment; 6 birds/cage) with 3 dietary Arg concentrations (1.05, 1.4...

  10. Dietary L-arginine supplementation modulates lipopolysaccharide-induced systemic inflammatory response in broiler chickens

    USDA-ARS?s Scientific Manuscript database

    This study was conducted to evaluate whether dietary supplementation with L-arginine (Arg) could attenuate lipopolysaccharide (LPS)-induced systemic inflammatory response through LPS/TLR-4 signaling pathway in broilers. The experiment was designed as a 2 × 3 factorial arrangement (n = 8 cages/treatm...

  11. L-arginine supplementation enhances exhaled NO, breath condensate VEGF, and headache at 4,342 m.

    PubMed

    Mansoor, Jim K; Morrissey, Brian M; Walby, William F; Yoneda, Ken Y; Juarez, Maya; Kajekar, Radhika; Severinghaus, John W; Eldridge, Marlowe W; Schelegle, Edward S

    2005-01-01

    We examined the effect of dietary supplementation with L-arginine on breath condensate VEGF, exhaled nitric oxide (NO), plasma erythropoietin, symptoms of acute mountain sickness, and respiratory related sensations at 4,342 m through the course of 24 h in seven healthy male subjects. Serum L-arginine levels increased in treated subjects at time 0, 8, and 24 h compared with placebo, indicating the effectiveness of our treatment. L-arginine had no significant effect on overall Lake Louise scores compared with placebo. However, there was a significant increase in headache within the L-arginine treatment group at 12 h compared with time 0, a change not seen in the placebo condition between these two time points. There was a trend (p = 0.087) toward greater exhaled NO and significant increases in breath condensate VEGF with L-arginine treatment, but no L-arginine effect on serum EPO. These results suggest that L-arginine supplementation increases HIF-1 stabilization in the lung, possibly through a NO-dependent pathway. In total, our observations indicate that L-arginine supplementation is not beneficial in the prophylactic treatment of AMS.

  12. Structural alterations in rat myocardium induced by chronic l-arginine and l-NAME supplementation.

    PubMed

    Hmaid, Amal Abdussalam Ali A; Markelic, Milica; Otasevic, Vesna; Masovic, Sava; Jankovic, Aleksandra; Korac, Bato; Korac, Aleksandra

    2018-03-01

    Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO) plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C) or cold (4 ± 1 °C) and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (N ω -nitro-l-arginine methyl ester)·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis.

  13. Dietary l-Arginine Supplementation Protects Weanling Pigs from Deoxynivalenol-Induced Toxicity

    PubMed Central

    Wu, Li; Liao, Peng; He, Liuqin; Feng, Zemeng; Ren, Wenkai; Yin, Jie; Duan, Jielin; Li, Tiejun; Yin, Yulong

    2015-01-01

    This study was conducted to determine the positive effects of dietary supplementation with l-arginine (Arg) on piglets fed a deoxynivalenol (DON)-contaminated diet. A total of eighteen, 28-day-old healthy weanling pigs were randomly assigned into one of three groups: uncontaminated basal diet (control group), 6 mg/kg DON-contaminated diet (DON group) and 6 mg/kg DON + 1% l-arginine (DON + ARG group). After 21 days of Arg supplementation, piglets in the DON and DON + ARG groups were challenged by feeding 6 mg/kg DON-contaminated diet for seven days. The results showed that DON resulted in damage to piglets. However, clinical parameters, including jejunal morphology, amino acid concentrations in the serum, jejunum and ileum, were improved by Arg (p < 0.05). Furthermore, the mRNA levels for sodium-glucose transporter-1 (SGLT-1), glucose transporter type-2 (GLUT-2) and y+l-type amino acid transporter-1 (y+LAT-1) were downregulated in the DON group, but the values were increased in the DON + ARG group (p < 0.05). Collectively, these results indicate that dietary supplementation with Arg exerts a protective role in pigs fed DON-contaminated diets. PMID:25884909

  14. Supplementation with apple enriched with L-arginine may improve metabolic control and survival rate in alloxan-induced diabetic rats.

    PubMed

    Escudero, Andrea; Petzold, Guillermo; Moreno, Jorge; Gonzalez, Marcelo; Junod, Julio; Aguayo, Claudio; Acurio, Jesenia; Escudero, Carlos

    2013-01-01

    Supplementation with L-arginine or fresh food with high content of this amino acid is associated with favorable effects in the metabolic control of diabetes. We aimed to determine whether supplementation with apples enriched with L-arginine offer additional benefits compared to L-arginine by itself in a preclinical study of diabetes. This study combines food-engineer technologies with in vivo and in vitro analysis. In vitro experiments show that cells derived from non-diabetic animals and exposed to high glucose (25 mM, 12 H) and cells isolated from alloxan-induced diabetic animals exhibited a reduction (∼50%) in the L-arginine uptake. This effect was reverted by L-arginine pretreatment (12 H) in both the normal and diabetes-derived cells. In preclinical studies, normoglycemic (n = 25) and diabetic groups (n = 50) were divided into subgroups that received either L-arginine (375 mg/kg per 10 days) or apple enriched with L-arginine or vehicle (control). In a preliminary analysis, supplementation with L-arginine by itself (50%) or apple enriched with L-arginine (100%) improve survival rate in the diabetic group compared to control (0%) at the end of the follow up (17 days). This phenomenon was associated with a partial but sustained high plasma level of L-arginine, as well as plasma concentration of nitrites and insulin in the L-arginine or apple + L-arginine groups after supplementation. Apple + L-arginine supplementation in diabetic animals induced the highest and longest effects in the level of these three markers among the studied groups. Therefore, apple enriched by L-arginine offers more benefits than L-arginine by itself in this preclinical study. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

  15. Aerobic training and l-arginine supplementation promotes rat heart and hindleg muscles arteriogenesis after myocardial infarction.

    PubMed

    Ranjbar, Kamal; Rahmani-Nia, Farhad; Shahabpour, Elham

    2016-09-01

    Arteriogenesis is a main defense mechanism to prevent heart and local tissues dysfunction in occlusive artery disease. TGF-β and angiostatin have a pivotal role in arteriogenesis. We tested the hypothesis that aerobic training and l-arginine supplementation promotes cardiac and skeletal muscles arteriogenesis after myocardial infarction (MI) parallel to upregulation of TGF-β and downregulation of angiostatin. For this purpose, 4 weeks after LAD occlusion, 50 male Wistar rats were randomly distributed into five groups: (1) sham surgery without MI (sham, n = 10), (2) control-MI (Con-MI, n = 10), (3) l-arginine-MI (La-MI, n = 10), (4) exercise training-MI (Ex-MI, n = 10), and (5) exercise and l-arginine-MI (Ex + La-MI). Exercise training groups running on a treadmill for 10 weeks with moderate intensity. Rats in the l-arginine-treated groups drank water containing 4 % l-arginine. Arteriolar density with different diameters (11-25, 26-50, 51-75, and 76-150 μm), TGF-β, and angiostatin gene expression were measured in cardiac (area at risk) and skeletal (soleus and gastrocnemius) muscles. Smaller arterioles decreased in cardiac after MI. Aerobic training and l-arginine increased the number of cardiac arterioles with 11-25 and 26-50 μm diameters parallel to TGF-β overexpression. In gastrocnemius muscle, the number of arterioles/mm(2) was only increased in the 11 to 25 μm in response to training with and without l-arginine parallel to angiostatin downregulation. Soleus arteriolar density with different size was not different between experimental groups. Results showed that 10 weeks aerobic exercise training and l-arginine supplementation promotes arteriogenesis of heart and gastrocnemius muscles parallel to overexpression of TGF-β and downregulation of angiostatin in MI rats.

  16. Exercise training reverses the negative effects of chronic L-arginine supplementation on insulin sensitivity.

    PubMed

    Salgueiro, Rafael Barrera; Gerlinger-Romero, Frederico; Guimarães-Ferreira, Lucas; de Castro Barbosa, Thais; Nunes, Maria Tereza

    2017-12-15

    L-Arginine has emerged as an important supplement for athletes and non-athletes in order to improve performance. Arginine has been extensively used as substrate for nitric oxide synthesis, leading to increased vasodilatation and hormonal secretion. However, the chronic consumption of arginine has been shown to impair insulin sensitivity. In the present study, we aimed to evaluate whether chronic arginine supplementation associated with exercise training would have a beneficial impact on insulin sensitivity. We, therefore, treated Wistar rats for 4weeks with arginine, associated or not with exercise training (treadmill). We assessed the somatotropic activation, by evaluating growth hormone (GH) gene expression and protein content in the pituitary, as well is GH concentration in the serum. Additionally, we evaluate whole-body insulin sensitivity, by performing an insulin tolerance test. Skeletal muscle morpho-physiological parameters were also assessed. Insulin sensitivity was impaired in the arginine-treated rats. However, exercise training reversed the negative effects of arginine. Arginine and exercise training increased somatotropic axis function, muscle mass and body weight gain. The combination arginine and exercise training further decreased total fat mass. Our results confirm that chronic arginine supplementation leads to insulin resistance, which can be reversed in the association with exercise training. We provide further evidence that exercise training is an important tool to improve whole-body metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Dietary L-arginine supplementation enhances intestinal development and expression of vascular endothelial growth factor in weanling piglets.

    PubMed

    Yao, Kang; Guan, Shu; Li, Tiejun; Huang, Ruilin; Wu, Guoyao; Ruan, Zheng; Yin, Yulong

    2011-03-01

    Oral administration of L-arginine has been reported to prevent gut disease in human infants. However, little is known about the effects of dietary arginine supplementation on intestinal development of weaned piglets. In the present study, twenty 21-d-old castrated piglets with 5·3 (SEM 0·13) kg body weight (BW) were weaned from sows, individually housed and randomly assigned to one of the two maize- and soyabean meal-based diets supplemented with 0 or 1% L-arginine. After consuming the diets for 7 d, six pigs were randomly selected from each group to obtain various tissues. Compared with control pigs, dietary supplementation with 1% L-arginine did not affect feed intake but enhanced (P<0·05) the relative weight of the small intestine (+33 %), daily BW gain (+38 %) and feed efficiency (+28 %). The villus height of the duodenum, jejunum and ileum in arginine-supplemented piglets was 21, 28 and 25% greater (P<0·05) than in the nonsupplemented control group. Arginine supplementation increased (P<0·05) protein levels for vascular endothelial growth factor(VEGF) in duodenal, jejunal and ileal mucosae by 14, 39 and 35 %, respectively. Compared with the control group, dietary supplementation with 1% L-arginine increased (P<0·05) plasma concentrations of arginine and insulin (+36 %), and decreased (P<0·05) plasma concentrations of cortisol (233 %), NH3 (221 %) and urea (219 %). These results indicate that arginine supplementation enhances intestinal growth, development and expression of VEGF in early-weaned pigs fed a maize- and soyabean meal-based diet. The findings may have important implications for neonatal pigs under stressful or diseased conditions.

  18. Plasma l-citrulline concentrations in l-arginine-supplemented healthy dogs.

    PubMed

    Flynn, K M; Kellihan, H B; Trepanier, L A

    2017-08-01

    To determine whether oral l-arginine increases plasma [l-citrulline] in dogs. Eleven healthy staff-owned dogs were used in this study. Dogs (n = 3) were given l-arginine (50mg/kg PO q8h) for 7 days, and plasma [l-arginine] and [l-citrulline] were analyzed by high performance liquid chromatography at baseline (BL), steady state trough, and 0.5, 1, 1.5, 2, 4, 6, and 8 h after final dosing on day 7. Eleven dogs were then treated with 100mg/kg l-arginine PO q8h for 7 days, and [l-arginine] and [l-citrulline] were measured at BL, steady state trough, and at peak 4 hrs after dosing (T4 hrs). - Plasma [l-arginine] and [l-citrulline] peaked at T4 hrs on the 50mg/kg dosage. Target outcome, modeled after human study results, of a doubling of [l-arginine] and a 25-30% increase in [l-citrulline] from BL were not reached. After the 100mg/kg dosage, plasma [l-arginine] increased from a BL median of 160.1 μM (range, 100.2-231.4 μM) to a peak of 417.4 μM (206.5-807.3 μM) at T4 hrs, and plasma [l-citrulline] increased from a BL median of 87.8 μM (59.1-117.1 μM) to peak of 102.2 μM (47.4-192.6 μM) at T4 hrs. Ten of eleven dogs showed a doubling of plasma [l-arginine] and 4/11 dogs achieved 25-30% or greater increases in plasma [l-citrulline]. No adverse effects on heart rate or blood pressure were noted. - Oral l-arginine dosage of 100mg/kg q8h doubles plasma [l-arginine] in healthy dogs, but conversion to l-citrulline is quite variable. Further evaluation of this dosage regimen in dogs with pulmonary hypertension is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Effect of L-arginine supplementation on immune responsiveness in patients with sickle cell disease.

    PubMed

    Scavella, Arnette; Leiva, Lily; Monjure, Hanh; Zea, Arnold H; Gardner, Renee V

    2010-08-01

    L-arginine (L-Arg) is deficient in sickle cell disease (SSD) during vasoocclusion. We investigated possible causal relationship between L-Arg deficiency and immune dysfunction in SSD in steady-state. Fifteen patients with SSD in steady-state and 13 controls were studied. Plasma L-Arg levels were measured using liquid chromatography. T cell subsets and CD3zeta (CD3zeta) chain expression were analyzed using flow cytometry. Lymphocyte proliferative response to phytohemagglutinin (PHA) and production of IL-6 and interferon-gamma (IFN-gamma) were evaluated with and without L-Arg. SSD patients had significantly lower L-Arg levels than controls. CD3 and CD19 cell populations were comparable for both groups, but SSD patients had above normal numbers of natural killer cells (P = 0.06). Patients and controls exhibited significantly increased lymphocyte blastogenesis to PHA after introduction of L-Arg to cultures; response of patients was significantly greater than values for control individuals. Proliferative response to candida in SSD patients was significantly lower than in controls; L-Arg supplementation did not increase this response. L-Arg had no effect on blastogenic response to PPD and candida albicans. No effect was likewise seen in production of IL-6 and IFN-gamma after addition of L-Arg. CD3zeta chain expression increased after addition of L-Arg in both groups; differences were insignificant. L-Arg levels in steady-state SSD are significantly lower than in controls. L-Arg supplementation enhanced lymphocyte blastogenesis to PHA for both controls and patients, but not in response to antigen. There were no significant differences in CD3zeta chain expression although upregulation of expression occurred after L-Arg supplementation for both groups. (c) 2010 Wiley-Liss, Inc.

  20. VO2max and ventilatory threshold of trained cyclists are not affected by 28-day L-arginine supplementation.

    PubMed

    Sunderland, Kyle L; Greer, Felicia; Morales, Jacobo

    2011-03-01

    The ergogenic effect of L-arginine on an endurance-trained population is not well studied. The few studies that have investigated L-arginine on this population have not been conducted in a laboratory setting or measured aerobic variables. The purpose of the current study is to determine if 28 days of L-arginine supplementation in trained male cyclists affects VO2max and ventilatory threshold (VT). Eighteen (18) endurance-trained male cyclists (mean ± SD, age: 36.3 ± 7.9 years; height: 182.4 ± 4.6 cm; and body mass: 79.5 ± 4.7 kg) performed a graded exercise test (GXT; 50 W + 25 W·min) before and after 28 days of supplementation with L-arginine (ARG; 2 × 6 g·d) or placebo (PLA; cornstarch). The GXT was conducted on the subject's own bicycle using the RacerMate CompuTrainer (Seattle, WA, USA). VO2 was continuously recorded using the ParvoMedics TrueOne 2400 metabolic cart (Salt Lake City, UT, USA) and VT was established by plotting the ventilatory equivalent for O2 (VE/VO2) and the ventilatory equivalent for CO2 (VE/VCO2) and identifying the point at which VE/VO2 increases with no substantial changes in VE/VCO2. L-arginine supplementation had no effect from initial VO2max (PL, 58.7 ± 7.1 ml·kg·min; ARG, 63.5 ± 7.3 ml·kg·min) to postsupplement VO2max (PL, 58.9 ± 6.0 ml·kg·min; ARG, 63.2 ± 7.2 ml·kg·min). Also, no effect was seen from initial VT (PL, 75.7 ± 4.6% VO2max; ARG, 76.0 ± 5.3% VO2max) to postsupplement VT (PL, 74.3 ± 8.1% VO2max; ARG, 74.2 ± 6.4% VO2max). These results indicate that L-arginine does not impact VO2max or VT in trained male cyclists.

  1. Effect of L-arginine dietary supplementation on salivary urea concentration and pH in physically active individuals.

    PubMed

    Vuletic, L; Spalj, S; Rogic, D; Ruzic, L; Alajbeg, I

    2013-12-01

    The aim of this study was to assess if the consumption of 3 g of a commercially available L-arginine dietary supplement causes a postabsorptive rise in urea concentration or pH of unstimulated saliva in a group of physically active individuals. Salivary urea and pH were determined for 117 participants in a randomized double-blinded placebo-controlled study. Samples were collected by 'spitting' method in fasting conditions. One hour prior to their second visit, participants consumed three tablets of L-arginine or placebo. Urea concentration was significantly lower at second measurement for both the study and control group. The magnitude of the change was not significant between the groups. pH was higher for both groups at second measurement, but only significant for the study group. The magnitude of the change was significant between the groups. Participants who intermittently ingested protein dietary supplements and those with a Body Mass Index (BMI) higher than 25 had significantly higher basal urea concentration. The results of this study did not confirm the hypothesis. Further studies are needed to determine the effects of different doses of L-arginine supplements on the biochemical composition of saliva and the influence of their long-term consumption on the risk of developing dental diseases. © 2013 Australian Dental Association.

  2. The acute effects of a low and high dose of oral L-arginine supplementation in young active males at rest.

    PubMed

    Forbes, Scott C; Bell, Gordon J

    2011-06-01

    L-arginine (2-amino-5-guanidinovaleric acid) is a conditionally essential amino acid. Intravenous (IV) administration of l-arginine invokes a large metabolic (nitrate/nitrite (NO(x))) and hormonal (growth hormone (GH), insulin-like growth factor 1 (IGF-1), and insulin) response; however, research examining oral l-arginine supplementation is conflicting, potentially owing to dose. The purpose of this study was examine a low and high dose of oral l-arginine on blood l-arginine, NO(x), GH, IGF-1, and insulin response. Fourteen physically active males (age: 25 ± 5 years; weight: 78.0 ± 8.5 kg; height: 179.4 ± 4.7 cm) volunteered to be in a randomized, double-blind, repeated-measures study. Following an overnight fast, an IV catheter was placed in a forearm vein and a resting blood sample was drawn at ∼0800 hours. Each subject was then provided 1 of 3 treatment conditions (placebo, low (0.075 g·kg(-1) of body mass), or high (0.15 g·kg(-1) of body mass of l-arginine)). Blood samples were drawn at 30, 60, 90, 120, and 180 min after consumption. l-arginine plasma concentrations significantly increased (p < 0.001) to a similar level at any time point in both the low- and high-dose conditions; there was no change over time in the placebo condition. There was no significant difference between conditions for NO(x), GH, IGF-1, or insulin. Based on these findings, a low dose of l-arginine was just as effective at increasing plasma l-arginine concentrations as a high dose; however, neither dose was able to promote a significant increase in NO(x), GH, IGF-1, or insulin at rest.

  3. Acute L-arginine alpha ketoglutarate supplementation fails to improve muscular performance in resistance trained and untrained men.

    PubMed

    Wax, Benjamin; Kavazis, Andreas N; Webb, Heather E; Brown, Stanley P

    2012-04-17

    Dietary supplements containing L-arginine are marketed to improve exercise performance, but the efficacy of such supplements is not clear. Therefore, this study examined the efficacy of acute ingestion of L-arginine alpha-ketoglutarate (AAKG) muscular strength and endurance in resistance trained and untrained men. Eight resistance trained and eight untrained healthy males ingested either 3000mg of AAKG or a placebo 45 minutes prior to a resistance exercise protocol in a randomized, double-blind crossover design. One-repetition maximum (1RM) on the standard barbell bench press and leg press were obtained. Upon determination of 1RM, subjects completed repetitions to failure at 60% 1RM on both the standard barbell bench press and leg press. Heart rate was measured pre and post exercise. One week later, subjects ingested the other supplement and performed the identical resistance exercise protocol. Our data showed statistical significant differences (p<0.05) between resistance trained and untrained males for both 1RM and total load volume (TLV; multiply 60% of 1RM times the number of repetitions to failure) for the upper body. However, 1RM and TLV were not statistically different (p>0.05) between supplementation conditions for either resistance trained or untrained men in the bench press or leg press exercises. Heart rate was similar at the end of the upper and lower body bouts of resistance exercise with AAKG vs. placebo. The results from our study indicate that acute AAKG supplementation provides no ergogenic benefit on 1RM or TLV as measured by the standard barbell bench press and leg press, regardless of the subjects training status.

  4. Dietary supplementation of l-arginine and chromium picolinate in sows during gestation affects the muscle fibre characteristics but not the performance of their progeny.

    PubMed

    Shi, Zhan; Song, Wentao; Sun, Yuecheng; Wang, Liansheng; Shi, Baoming; Shan, Anshan; Bi, Zhongpeng

    2018-01-01

    The present study investigated the effects of dietary supplementation of l-arginine and chromium picolinate (CrP) in sows during gestation on muscle fibre characteristics, performance and carcass characteristics of their progeny. Sixty healthy sows were randomly divided into four groups as a 2 × 2 factorial experiment design: one group received the control diet, another received the control diet + 10 g kg -1 l-arginine, the third group received the control diet + 400 ppb CrP, and the fourth group received the control diet + 10 g kg -1 l-arginine and 400 ppb CrP. The results showed that sows fed the diet supplemented with CrP produced progeny with higher muscle fibre numbers at birth, weaning and slaughter compared to sows fed the control diet. For mean fibre areas, the same result was found at weaning. For progeny of sows fed diets supplemented with l-arginine, only higher muscle fibre numbers at slaughter was observed. Almost no differences were observed regarding average daily gains, average daily feed intake, gain-to-feed ratios, carcass and meat traits. The results of the present study indicate that dietary supplementation of l-arginine and particularly CrP in sows during gestation alters muscle fibre numbers in their offspring, although not their performance or carcass characteristics. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  5. The effect of l-arginine supplementation on body composition and performance in male athletes: a double-blinded randomized clinical trial.

    PubMed

    Pahlavani, N; Entezari, M H; Nasiri, M; Miri, A; Rezaie, M; Bagheri-Bidakhavidi, M; Sadeghi, O

    2017-04-01

    Athletes used a lot of dietary supplements to achieve the more muscle mass and improve their athletic performance. The objective of this study was to investigate the effect of l-arginine supplementation on sport performance and body composition in male soccer players. This double-blinded, randomized and placebo-controlled trial was conducted on 56 male soccer players, with age range of 16-35, who referred to sport clubs in Isfahan, Iran. Subjects were randomly assigned to either l-arginine or placebo groups. Athletes received daily either 2 g per day l-arginine supplement or the same amount of placebo (maltodextrin) for 45 days. Sport performance and also body mass index (BMI), body fat mass (BFM) and lean body mass (LBM) were measured at the beginning and end of the study. Also, 3-day dietary records were collected at three different time points (before, in the middle of, and at the end of the study). The mean age of subjects was 20.85±4.29 years. Sport performance (VO 2 max) significantly increased in l-arginine supplementation group (4.12±6.07) compared with placebo group (1.23±3.36) (P=0.03). This increase remained significant even after adjustment of baseline values, physical activity and usual dietary intake of subjects throughout the study. No significant effect of l-arginine supplementation was found on weight, BMI, BFM and LBM. l-arginine supplementation (2 g per day) could increase the sport performance in male athletes, but had no effect on anthropometric measurements, including BMI, BFM and LBM. So, further studies are needed to shed light our findings.

  6. L-Arginine supplementation 0.5% of diet during the last 90 days of gestation and 14 days postpartum reduced uterine fluid accumulation in the broodmare.

    PubMed

    Mesa, A M; Warren, L K; Sheehan, J M; Kelley, D E; Mortensen, C J

    2015-08-01

    L-Arginine is an essential amino acid in many species that has been shown to influence reproduction. However, in horses a dose of 1% L-arginine of total dietary intake impaired absorption of other amino acids, whereas a dose of 0.5% did not. The objectives of this experiment were to evaluate postpartum parameters on mares supplemented with 0.5% L-arginine through the last 90d of gestation and 14d postpartum. Sixteen light-horse mares were randomly divided in two groups: 8 mares supplemented with 0.5% L-arginine and 8 mares fed an isonitrogenous equivalent. Gestation length, days to uterine clearance and days to first ovulation were compared. Uterine body depth, diameter of uterine horns, and length of largest pocket of uterine fluid were recorded daily via transrectal ultrasound. Measurements of foal weight, height, and cannon bone circumference were recorded for 9 weeks. Arginine treatment had no effect on gestation length (P=0.58). Supplemented mares cleared fluid quicker postpartum (6.8±0.53d; P=0.026) compared to control (9.0±0.38d). Mares supplemented with L-arginine had smaller diameter of fluid present in the postpartum uterus (P≤0.05). Days to first postpartum ovulation were not affected by treatment nor any influence on uterine involution. Finally, treatment had no effect on any foal's measured parameters. L-Arginine supplementation fed at 0.5% of daily intake during the last 90d of gestation and early postpartum in mares decreased uterine fluid accumulation, yet did not appear to have any effect on any other parameters measured. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial

    PubMed Central

    Perichart-Perera, Otilia; Espino, Salvador; Avila-Vergara, Marco Antonio; Ibarra, Isabel; Ahued, Roberto; Godines, Myrna; Parry, Samuel; Macones, George; Strauss, Jerome F

    2011-01-01

    Objective To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk. Design Randomised, blinded, placebo controlled clinical trial. Setting Tertiary public hospital in Mexico City. Participants Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery. Interventions Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy. Main outcome measure Development of pre-eclampsia/eclampsia. Results 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ2=19.41; P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ2=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14). Conclusions Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be

  8. Cardioprotective activity of placental growth factor combined with oral supplementation of l-arginine in a rat model of acute myocardial infarction.

    PubMed

    Luo, Liyun; Chen, Bairong; Huang, Yin; Liang, Zibin; Li, Songbiao; Yin, Yuelan; Chen, Jian; Wu, Wei

    2016-01-01

    Exogenous administration of placental growth factor (PlGF) stimulates angiogenesis and improves ventricular remodeling after acute myocardial infarction (AMI), and supplementation with l-arginine ameliorates endothelial function. The objective of the present study was to compare the cardioprotective effects of combination therapy of PlGF and l-arginine with those of direct administration of PlGF alone in a rat model of AMI. Fifty male Sprague Dawley rats were randomly divided into five groups: sham group, normal saline group, l-arginine group, PlGF group, and combination group (PlGF + l-arginine). An AMI rat model was established by ligation of the left anterior descending of coronary arteries. After 4 weeks of postligation treatment, cardiac function, scar area, angiogenesis and arteriogenesis, myocardial endothelial nitric oxide synthase (eNOS) and collagen I protein content, and plasma concentration of brain natriuretic peptide (BNP) were studied. Echocardiography, Masson's staining, immunohistochemical analyses, Western blot, and enzyme-linked immunosorbent assay were performed. Left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), and capillary and arteriole densities were higher in the PlGF group than in the normal saline group ( P <0.01). Scar area, collagen I protein content, and plasma concentration of BNP were decreased in the PlGF group ( P <0.01). Myocardial eNOS protein level was elevated in the l-arginine group and PlGF + l-arginine group ( P <0.01). Compared with the PlGF group, LVEF, LVFS, myocardial eNOS, and capillary and arteriole densities were higher in the combination group ( P <0.01). Scar area, content of collagen I protein, and plasma concentration of BNP were reduced in the combination group ( P <0.01). Exogenous administration of PlGF stimulates angiogenesis and improves cardiac function. l-arginine increases the expression of the eNOS protein. PlGF and l-arginine have a more pronounced, synergistic

  9. Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat.

    PubMed

    Koppelmann, Tal; Pollak, Yulia; Mogilner, Jorge; Bejar, Jacob; Coran, Arnold G; Sukhotnik, Igor

    2012-04-30

    Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat. Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression. MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels. Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat.

  10. Dietary L-arginine supplementation reduces Methotrexate-induced intestinal mucosal injury in rat

    PubMed Central

    2012-01-01

    Background Arginine (ARG) and nitric oxide maintain the mucosal integrity of the intestine in various intestinal disorders. In the present study, we evaluated the effects of oral ARG supplementation on intestinal structural changes, enterocyte proliferation and apoptosis following methotrexate (MTX)-induced intestinal damage in a rat. Methods Male rats were divided into four experimental groups: Control rats, CONTR-ARG rats, were treated with oral ARG given in drinking water 72 hours before and 72 hours following vehicle injection, MTX rats were treated with a single dose of methotrexate, and MTX-ARG rats were treated with oral ARG following injection of MTX. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 72 hours following MTX injection. RT-PCR was used to determine bax and bcl-2 mRNA expression. Results MTX-ARG rats demonstrated greater jejunal and ileal bowel weight, greater ileal mucosal weight, greater ileal mucosal DNA and protein levels, greater villus height in jejunum and ileum and crypt depth in ileum, compared to MTX animals. A significant decrease in enterocyte apoptosis in the ileum of MTX-ARG rats (vs MTX) was accompanied by decreased bax mRNA and protein expression and increased bcl-2 protein levels. Conclusions Treatment with oral ARG prevents mucosal injury and improves intestinal recovery following MTX- injury in the rat. PMID:22545735

  11. Novel therapy for pyridoxine dependent epilepsy due to ALDH7A1 genetic defect: L-arginine supplementation alternative to lysine-restricted diet.

    PubMed

    Mercimek-Mahmutoglu, Saadet; Cordeiro, Dawn; Cruz, Vivian; Hyland, Keith; Struys, Eduard A; Kyriakopoulou, Lianna; Mamak, Eva

    2014-11-01

    Pyridoxine dependent epilepsy (PDE) due to mutations in the ALDH7A1 gene (PDE-ALDH7A1) is caused by α-aminoadipic-semialdehyde-dehydrogenase enzyme deficiency in the lysine pathway resulting in the accumulation of α-aminoadipic acid semialdehyde (α-AASA). Classical presentation is neonatal intractable seizures with a dramatic response to pyridoxine. Pyridoxine therapy does not prevent developmental delays in the majority of the patients. We hypothesized that L-arginine supplementation will decrease accumulation of α-AASA by competitive inhibition of lysine transport into the central nervous system and improve neurodevelopmental and neurocognitive functions in PDE-ALDH7A1. A 12-year-old male with PDE-ALDH7A1 was treated with l-arginine supplementation as an innovative therapy. Treatment outcome was monitored by cerebral-spinal-fluid (CSF) α-AASA measurements at baseline, 6th and 12th months of therapy. Neuropsychological assessments were performed at baseline and 12th months of therapy. L-arginine therapy was well tolerated without side effects. CSF α-AASA was decreased 57% at 12th months of therapy. Neuropsychological assessments revealed improvements in general abilities index from 108 to 116 and improvements in verbal and motor functioning at 12th months of therapy. The short-term treatment outcome of this novel L-arginine supplementation therapy for PDE-ALDH7A1 was successful for biochemical and neurocognitive improvements. Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  12. Improvement of seminal quality and sexual function of men with oligoasthenoteratozoospermia syndrome following supplementation with L-arginine and Pycnogenol®.

    PubMed

    Kobori, Yoshitomo; Suzuki, Keisuke; Iwahata, Toshiyuki; Shin, Takeshi; Sadaoka, Yuko; Sato, Ryo; Nishio, Kojiro; Yagi, Hiroshi; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi; Strong, Jeffry Michael; Rohdewald, Peter

    2015-09-30

    We evaluated the effectiveness of antioxidant co-supplementation therapy using Larginine and Pycnogenol(®) in Japanese men with oligoasthenozoospermia and mild erectile dysfunction (ED). A total of forty-seven adult males with oligoasthenoteratozoospermia syndrome (OAT) were eligible for enrollment. The effectiveness of supplementation with a combination of L-arginine 690 mg and French maritime pine bark extract (Pycnogenol(®)) 60mg for OAT and ED was investigated. The sperm concentration was enhanced significantly after treatment 2 and 4 months (11.79 ± 9.86 to 21.22 ± 28.17 and 20.15 ± 23.99 × 106/ml). Significant improvements in the International Index of Erectile Function (IIEF) were observed in the total score of IIEF (57.69 ± 11.04 to 59.43 ± 12.57) and domain of Orgasmic Function (9.01 ± 1.92 to 9.34 ± 1.66) after 4 months of treatment. L-arginine acts to increase the production of nitric oxide and Pycnogenol(®) activates the endothelial nitric oxide synthase and it is a potent antioxidant and inhibitor of inducible nitric oxide synthase. This study suggests that the combination of Pycnogenol(®) and L-arginine (Edicare(®)) is helpful for infertile men to ameliorate simultaneously quality of sperms as well as erectile functions.

  13. Dietary L-arginine supplementation during mouse gestation enhances reproductive performance and Vegfr2 transcription activity in the fetoplacental unit

    USDA-ARS?s Scientific Manuscript database

    Regarded as one of the most versatile amino acids, arginine serves as a precursor for many molecules and has been reported to improve the reproductive performance of rats and pigs. To this end, we sought to determine if dietary L-arginine alters fetoplacental vascular endothelial growth factor recep...

  14. L-Arginine

    MedlinePlus

    ... SAFE when taken by mouth appropriately for a short-term during pregnancy. Not enough is known about using L-arginine long-term in pregnancy or during breast-feeding. Stay on the safe side and avoid use. Children: L-arginine is POSSIBLY SAFE when used by ...

  15. L-arginine supplementation prevents increases in intestinal permeability and bacterial translocation in male Swiss mice subjected to physical exercise under environmental heat stress.

    PubMed

    Costa, Kátia Anunciação; Soares, Anne Danieli Nascimento; Wanner, Samuel Penna; Santos, Rosana das Graças Carvalho dos; Fernandes, Simone Odília Antunes; Martins, Flaviano dos Santos; Nicoli, Jacques Robert; Coimbra, Cândido Celso; Cardoso, Valbert Nascimento

    2014-02-01

    Dietary supplementation with l-arginine has been shown to improve the intestinal barrier in many experimental models. This study investigated the effects of arginine supplementation on the intestinal permeability and bacterial translocation (BT) induced by prolonged physical exercise under heat stress. Under anesthesia, male Swiss mice (5-wk-old) were implanted with an abdominal sensor to record their core body temperature (T(core)). After recovering from surgery, the mice were divided into 3 groups: a non-supplemented group that was fed the standard diet formulated by the American Institute of Nutrition (AIN-93G; control), a non-supplemented group that was fed the AIN-93G diet and subjected to exertional hyperthermia (H-NS), and a group supplemented with l-arginine at 2% and subjected to exertional hyperthermia (H-Arg). After 7 d of treatment, the H-NS and H-Arg mice were forced to run on a treadmill (60 min, 8 m/min) in a warm environment (34°C). The control mice remained at 24°C. Thirty min before the exercise or control trials, the mice received a diethylenetriamine pentaacetic acid (DTPA) solution labeled with technetium-99m ((99m)Tc-DTPA) or (99m)Tc-Escherichia coli by gavage to assess intestinal permeability and BT, respectively. The H-NS mice terminated the exercise with T(core) values of ∼40°C, and, 4 h later, presented a 12-fold increase in the blood uptake of (99m)Tc-DTPA and higher bacterial contents in the blood and liver than the control mice. Although supplementation with arginine did not change the exercise-induced increase in T(core), it prevented the increases in intestinal permeability and BT caused by exertional hyperthermia. Our results indicate that dietary l-arginine supplementation preserves the integrity of the intestinal epithelium during exercise under heat stress, acting through mechanisms that are independent of T(core) regulation.

  16. Sperm quality in men is improved by supplementation with a combination of L-arginine, L-citrullin, roburins and Pycnogenol®.

    PubMed

    Stanislavov, R; Rohdewald, P

    2014-12-01

    The aim of this study was to investigate the influence of Prelox®R, a combination of French maritime pine bark extract (Pycnogenol®), L-arginine, L-citrulline and roburins, on male fertility. Sperm quality of 50 subfertile men was tested in monthly intervals in a double-blind, randomized, placebo controlled, crossover study. Patients received 2 tablets Prelox®R or placebo twice daily during test periods. Following a run-in period of 1 month, patients received either Prelox®R or a placebo for 1 month. After a wash-out period of 1 month, patients received Prelox®R or a placebo in a crossover manner for 1 month. Sperm volume, concentration of spermatozoa, total count, motility, vitality and morphology were measured by standard methods of calculation of the Fertility Index (FI) in monthly intervals. Activity of e-NOS in sperm was evaluated in parallel by measuring the quantity of L-citulline produced from L-arginine. Supplementation with Prelox®R enhanced sperm volume and concentration, motility, vitality and morphology significantly versus placebo. The Fertility Index rose to normal values during treatment with Prelox®R. e-NOS activity in sperm was elevated by Prelox®R. No adverse effects were reported. Prelox®R offers a safe method to improve quality of human spermatozoa in subfertile men.

  17. Effects of supplemental L-arginine on the intestinal adaptive response after massive small-bowel resection in rats.

    PubMed

    Oztürk, Hayrettin; Dokucu, Ali Ihsan; Yağmur, Yusuf; Sari, Ibrahim

    2002-09-01

    To evaluate whether L-arginine methyl ester (L-Arg) can improve the structure of the small intestine and enhance adaptation in an experimental model of short-bowel syndrome (SBS), 40 Sprague-Dawley rats were divided randomly into four groups of 10 each. In one group only a laparotomy was performed (G1). The remaining 30 rats underwent 90% small-bowel resection (SBR) and formed the three experimental groups: the SBR/untreated group (G2), the SBR/L-NAME-treated group (G3), and the SBR/ L-Arg-treated group (G4). Rats in G2 received no therapeutic treatment. Rats in the SBR/L-NAME and SBR/L-Arg treated groups received N-G-nitro-L-arginine-methyl ester (L-NAME) and L-Arg intraperitoneally for 3 weeks, respectively. The animals were weighed daily. All rats underwent a relaparotomy on day 21 of the experiment. Remnant small bowel was excised and evaluated for villus height and crypt cell mitoses. After the 90% SBR, all animals had from diarrhea and weight loss between the 1st and 6th postoperative days (POD). The body weight of the SBR/L-Arg group showed significant increases at POD 10 and 21 in comparison to the SBR/untreated and SBR/L-NAME groups (P < 0.001). The rats treated with L-Arg had significantly greater villus height and crypt-cell mitoses compared to the other groups (P < 0.0001, P < 0.001). These observations suggest that L-Arg treatment increases villus height and crypt-cell mitoses after massive SBR and may play a considerable role in the mucosal adaptive response in SBS in rats.

  18. Acute L-arginine supplementation has no effect on cardiovascular or thermoregulatory responses to rest, exercise, and recovery in the heat.

    PubMed

    Tyler, Christopher J; Coffey, Thomas R M; Hodges, Gary J

    2016-02-01

    To investigate the effect of acute L-arginine (L-ARG) supplementation on cardiovascular and thermoregulatory responses to rest, exercise, and recovery in the heat. Eight healthy men (age 27 ± 6 years; stature 176 ± 6 cm; body mass 76 ± 4 kg; maximal power output 237 ± 39 W) participated in a double-blind, crossover study, attending the laboratory for two experimental trials. On each occasion, participants consumed 500 ml of a black currant-flavoured cordial beverage 30 min before completing a 90 min experiment in the heat (35 °C and 50% rh). The experiment consisted of 30 min of seated rest, followed by 30 min submaximal cycling (60% maximal power output) and 30 min passive seated recovery. On one visit the drink contained 10 g of dissolved L-ARG while on the other visit it did not. L-ARG supplementation increased plasma L-ARG concentrations (peak +223 ± 80% after 60 min of the 90 min experiment); however, supplementation had no effect on rectal temperature, mean skin temperature, heart rate, arterial pressure, forearm skin vascular conductance, oxygen consumption or sweat loss at rest, during exercise, or during recovery in the heat (p > 0.05). Acute ingestion of 10 g L-ARG supplementation failed to elicit any changes in the cardiovascular or thermoregulatory responses to active or passive heat exposure in young, healthy males.

  19. Dietary L-arginine supplement alleviates hepatic heat stress and improves feed conversion ratio of Pekin ducks exposed to high environmental temperature.

    PubMed

    Zhu, W; Jiang, W; Wu, L Y

    2014-12-01

    The current intensive indoor production system of commercial Pekin ducks never allows adequate water for swimming or wetting. Therefore, heat stress is a key factor affecting health and growth of ducks in the hot regions and season. Experiment 1 was conducted to study whether heat stress was deleterious to certain organs of ducks. Forty-one-day-old mixed-sex Pekin ducks were randomly allocated to four electrically heated battery brooders comprised of 10 ducks each. Ducks were suddenly exposed to 37 °C ambient temperature for 3 h and then slaughtered, in one brooder at 21 days and in another brooder at 49 days of age. The results showed that body weight and weight of immune organs, particularly liver markedly decreased in acute heat stress ducks compared with the control. Experiment 2 was carried out to investigate the influences of dietary L-arginine (Arg) supplement on weight and compositions of certain lymphoid organs, and growth performance in Pekin ducks, under daily cyclic hot temperature environment. A total of 151-day-old mixed-sex Pekin ducks were randomly divided into one negative control and two treatment groups, fed experimental diets supplemented with 0, 5, and 10 g L-Arginine (L-Arg)/kg to the basal diet respectively. Ducks were exposed to cyclic high temperature simulating natural summer season. The results showed that the addition of L-Arg improves feed conversion ratio (FCR) during a period of 7-week trial, as well as increases hepatic weight relative to body weight at 21 days, while decreases the hepatic water content at 49 days of age. This study indicated that the liver was more sensitive to acute heat stress, and the hepatic relative weight and chemical composition could be regulated by dietary L-Arg supplementation in Pekin ducks being reared at high ambient temperature. These beneficial effects of Arg on liver might be a cause of improved FCR. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

  20. The effect of pumpkin (Cucurbita pepo L) seeds and L-arginine supplementation on serum lipid concentrations in atherogenic rats.

    PubMed

    Abuelgassim, Abuelgassim O; Al-showayman, Showayman I A

    2012-01-01

    The present study aimed to examine the effect of pumpkin (Cucurbita pepo L.) seeds supplementation on atherogenic diet-induced atherosclerosis. Rat were divided into two main groups , normal control and atherogenic control rats , each group composed of three subgroups one of them supplemented with 2% arginine in drinking water and the other supplemented with pumpkin seeds in diet at a concentration equivalent to 2% arginine. Supplementation continued for 37 days. Atherogenic rats supplemented with pumpkin seeds showed a significant decrease (p<0.001) in their serum concentrations of total cholesterol and LDL - C as they dropped from 4.89 mmol / L to 2.55 mmol /L and from 3.33 mmol / L to 0.70 mmol / L respectively. Serum concentrations of HDL-C were also significantly elevated in the same group. Although, atherogenic rats supplemented with 2% arginine showed significant increase in serum concentration of HDL-C, no significant changes were observed in their serum concentrations of total cholesterol and LDL-C. Our results showed that treatment of atherogenic rats with pumpkin seeds significantly decreased serum concentrations of TC and LDL-C. Our findings suggest that pumpkin seeds supplementation has a protective effect against atherogenic rats and this protective effect was not attributed to the high arginine concentrations in pumpkin seeds.

  1. An l-Arginine supplement improves broiler hypertensive response and gut function in broiler chickens reared at high altitude

    NASA Astrophysics Data System (ADS)

    Khajali, Fariborz; Moghaddam, Maryam Heydary; Hassanpour, Hossein

    2014-08-01

    An experiment was carried out to examine the effects of supplemental dietary arginine (ARG) on growth, hypertensive response, and gut function in broilers reared at high altitude (2,100 m). A total of 120 day-old male broilers (Cobb 500) were divided equally into two treatment groups. Treatments included a control basal diet composed of corn and soybean meal and an experimental diet to which an l-ARG supplement was added at 10 g/kg. The trial lasted for 42 days. There were no treatment differences with regard to feed intake, body weight gain, or feed conversion ratio. However ARG supplementation did increase the plasma concentration of nitric oxide, a potent vasodilator ( P < 0.05), and attenuated indices of pulmonary hypertension as reflected by reductions in the hematocrit and the right to total ventricular weight ratio ( P < 0.05). Significantly enhanced intestinal mucosal development was observed in broilers receiving ARG supplement when compared with controls ( P < 0.05), suggesting that ARG supplementation increased the absorptive surface area of the jejunum and ileum. In conclusion, broiler diets supplemented with ARG beneficially improved pulmonary hemodynamics and appeared to enhance gut function.

  2. Effect of L-arginine supplementation on the hepatic phosphatidylinositol 3-kinase signaling pathway and gluconeogenic enzymes in early intrauterine growth-restricted rats

    PubMed Central

    Luo, Kaiju; Chen, Pingyang; Li, Suping; Li, Wen; He, Mingfeng; Wang, Tao; Chen, Juncao

    2017-01-01

    The present study aimed to investigate the response of the phosphatidylinositol 3-kinase (PI3K) signaling pathway and gluconeogenic enzymes in intrauterine growth-restricted rats to dietary L-arginine (L-Arg) supplementation during the lactation period early in life. Pregnant Sprague-Dawley rats were randomly divided into a control group (CON), an intrauterine growth restriction group (IUGR) and an L-Arg group (LA). The pregnant rats in the CON group were fed a 21% protein diet, and those in the IUGR and LA groups were fed a 10% low protein diet, and all rats were fed a 21% protein diet after delivery. Water was available ad libitum to the pregnant rats during the 21-day lactation period, and the water provided to the LA group included 200 mg/kg/day L-Arg. Blood glucose, serum insulin, homeostasis model of assessment for insulin resistance (HOMA-IR), PI3K and protein kinase B (PKB) protein expression, and phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase) mRNA expression in the offspring rats were measured postnatally at 1, 3 and 8 weeks. No significant difference in blood glucose, serum insulin and HOMA-IR were identified at any time point among the three groups. PI3K and PKB expression was lower in the IUGR group offspring compared with that in the CON group offspring, but both were increased by dietary L-Arg supplementation. PEPCK mRNA and G-6-Pase mRNA expression levels in the offspring of the IUGR group were higher compared with those in the CON group but were downregulated following L-Arg supplementation. These results suggest that dietary L-Arg supplementation during the early lactation period promoted catch-up growth and reversed abnormalities in hepatic insulin signaling and gene expression of gluconeogenic enzymes in IUGR offspring rats. PMID:28962167

  3. Supplemental dietary L-arginine attenuates intestinal mucosal disruption during a coccidial vaccine challenge in broiler chickens

    USDA-ARS?s Scientific Manuscript database

    The present study investigated the effects of dietary arginine (Arg) supplementation on intestinal barrier integrity in broiler chickens undergoing coccidial challenge. The design of this study was a randomized complete block employing a 3 x 2 factorial arrangement (n = 8) with 3 level of Arg (1.11,...

  4. Treatment of Creatine Transporter (SLC6A8) Deficiency With Oral S-Adenosyl Methionine as Adjunct to L-arginine, Glycine, and Creatine Supplements.

    PubMed

    Jaggumantri, Sravan; Dunbar, Mary; Edgar, Vanessa; Mignone, Cristina; Newlove, Theresa; Elango, Rajavel; Collet, Jean Paul; Sargent, Michael; Stockler-Ipsiroglu, Sylvia; van Karnebeek, Clara D M

    2015-10-01

    Creatine transporter (SLC6A8) deficiency is an X-linked inborn error of metabolism characterized by cerebral creatine deficiency, behavioral problems, seizures, hypotonia, and intellectual developmental disability. A third of patients are amenable to treatment with high-dose oral creatine, glycine, and L-arginine supplementation. Given the limited treatment response, we initiated an open-label observational study to evaluate the effect of adjunct S-adenosyl methionine to further enhance intracerebral creatine synthesis. Significant and reproducible issues with sleep and behavior were noted in both male patients on a dose of 50/mg/kg. One of the two patients stopped S-adenosyl methionine and did not come for any follow-up. A safe and tolerable dose (17 mg/kg/day) was identified in the other patient. On magnetic resonance spectroscopy, this 8-year-old male did not show an increase in intracerebral creatine. However, significant improvement in speech/language skills, muscle mass were observed as well as in personal outcomes as defined by the family in activities related to communication and decision making. Further research is needed to assess the potential of S-adenosyl methionine as an adjunctive therapy for creatine transporter deficiency patients and to define the optimal dose. Our study also illustrates the importance of pathophysiology-based treatment, individualized outcome assessment, and patient/family participation in rare diseases research. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Dietary L-arginine supplementation improves the intestinal development through increasing mucosal Akt and mammalian target of rapamycin signals in intra-uterine growth retarded piglets.

    PubMed

    Wang, Yuanxiao; Zhang, Lili; Zhou, Genlai; Liao, Zhiyong; Ahmad, Hussain; Liu, Wenbin; Wang, Tian

    2012-10-28

    Intra-uterine growth retardation (IUGR) impairs postnatal growth and development of the small intestine (SI) in neonatal pigs and infants. L-Arginine (Arg), a critical amino acid involved in promoting growth and metabolism in young mammals, is more deficient in IUGR fetuses. However, little is known whether dietary Arg supplementation would accelerate the impaired development of the SI induced by IUGR in piglets. In the present study, a total of six litters of newborn piglets were used. In each litter, one normal and two IUGR littermates were obtained. Piglets were fed milk-based diets supplemented with 0 (Normal), 0 (IUGR) and 0·60% Arg (IUGR+Arg) from 7 to 14 d of age, respectively. Compared with Normal piglets at 14 d of age, IUGR decreased (P < 0·05) the growth performance, entire SI weight, and villus height in the jejunum and ileum. IUGR piglets had lower (P < 0·05) mucosal concentrations of Arg, insulin, insulin growth factor 1, as well as phosphorylated Akt, mammalian target of rapamycin (mTOR) and p70 S6 kinase but higher (P < 0·05) enterocyte apoptosis index (AI). After Arg treatment in IUGR piglets, the growth performance, weight of entire SI and mucosa, and villus height in the jejunum and ileum were increased (P < 0·05). Diet supplemented with Arg also increased (P < 0·05) the levels of Arg, insulin, phosphorylated Akt and mTOR in SI mucosa of IUGR piglets, and decreased (P < 0·05) the AI and caspase-3 activity. In conclusion, Arg has a beneficiary effect in improving the impaired SI development in IUGR piglets via regulating cell apoptosis and activating Akt and mTOR signals in SI mucosa.

  6. Supplemental dietary L-arginine attenuates intestinal mucosal disruption during a coccidial vaccine challenge in broiler chickens.

    PubMed

    Tan, Jianzhuang; Applegate, Todd J; Liu, Shasha; Guo, Yuming; Eicher, Susan D

    2014-10-14

    The present study investigated the effects of dietary arginine (Arg) supplementation on intestinal structure and functionality in broiler chickens subjected to coccidial challenge. The present study was a randomised complete block design employing a 3 × 2 factorial arrangement (n 8) with three dietary concentrations of Arg (11·1, 13·3 and 20·2 g/kg) with or without coccidial vaccine challenge (unchallenged and coccidial challenge). On day 14, birds were orally administered with coccidial vaccine or saline. On day 21, birds were killed to obtain jejunal tissue and mucosal samples for histological, gene expression and mucosal immunity measurements. Within 7 d of the challenge, there was a decrease in body-weight gain and feed intake, and an increase in the feed:gain ratio (P< 0·05). Jejunal inflammation was evidenced by villus damage, crypt dilation and goblet cell depletion. Coccidial challenge increased mucosal secretory IgA concentration and inflammatory gene (iNOS, IL-1β, IL-8 and MyD88) mRNA expression levels (P< 0·05), as well as reduced jejunal Mucin-2, IgA and IL-1RI mRNA expression levels (P< 0·05). Increasing Arg concentration (1) increased jejunal villus height (P< 0·05) and linearly increased jejunal crypt depth (P< 0·05); (2) quadratically increased mucosal maltase activity (P< 0·05) and linearly decreased mucosal secretory IgG concentration (P< 0·05) within the coccidiosis-challenged groups; and (3) linearly decreased jejunal Toll-like receptor 4 (TLR4) mRNA expression level (P< 0·05) within the coccidiosis-challenged groups. The mRNA expression of mechanistic target of rapamycin (mTOR) complex 1 pathway genes (mTOR and RPS6KB1) and the anti-apoptosis gene Bcl-2 quadratically responded to increasing dietary Arg supplementation (P< 0·05). These results indicate that dietary Arg supplementation attenuates intestinal mucosal disruption in coccidiosis-challenged chickens probably through suppressing TLR4 and activating m

  7. Effects of nutritional supplementation with l-arginine on repair of injuries due to muscle strain: experimental study on rats☆

    PubMed Central

    Couto, Lauren Izabel Medeiros; Wuicik, William Luiz; Kuhn, Ivan; Capriotti, Juan Rodolfo Vilela; Repka, João Carlos

    2015-01-01

    Objective To evaluate the influence of oral supplementation with arginine on regeneration of injuries due to straining of the anterior tibial muscle of rats. Methods Twenty-four Wistar rats of weight 492.5 ± 50.45 g were used. Injuries were induced through straining the anterior tibial muscles. The rats were separated into three groups of eight rats each. In the untreated group (UTG), after induction of injuries, the rats were observed for 24 h. In the simulation group (SG) and the arginine group (AG) respectively, the rats received isotonic saline solution and arginine solution via direct gavage, over a seven-day period. At the end of the period, blood samples were collected for serum evaluations of creatine kinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST) and C-reactive protein (CRP). The right and left anterior tibial muscles were resected for histopathological evaluations on the muscle injuries, investigating edema, hemorrhage and disorganization or morphometric alteration of the muscle fibers. The tissue repair was investigated in terms of proliferation of adipose tissue, angiogenesis and collagen fibers. The ANOVA and Student's t methods were used and p ≤ 0.05 was taken to be statistically significant. Results In the serum evaluations, the AG showed lower CK assay values and higher AST values. In the histopathological evaluation, the UTG presented edema and hemorrhage compatible with injuries due to strain; the SG presented edema and hemorrhage with proliferation of adipose tissue and collagen fibers; and the AG presented not only the findings of the SG but also, especially, intense angiogenesis. Conclusion Oral supplementation with arginine did not cause any significant metabolic alterations that would contraindicate its use and it induced angiogenesis during the repair of muscles injured due to strain. PMID:26401505

  8. Effects of a supplement combining Pycnogenol® and l-arginine aspartate on lower urinary dysfunction compared with saw palmetto extract.

    PubMed

    Yagi, Hiroshi; Sato, Ryo; Nishio, Kojiro; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

    2017-01-01

    Lower urinary tract symptoms (LUTS) and sexual dysfunction (SDys) are common problems that affect quality of life (QOL) in elderly men. In addition to prescribed drugs, many over-the-counter medications including supplements are used to treat QOL diseases. Phosphodiesterase inhibitors are reported to be effective for both LUTS and SDys by increasing nitric oxide levels. French maritime pine bark extract Pycnogenol ® , which is a potent nitric oxide donor, is reported to be effective for SDys. However, no reports have been published on whether it ameliorates LUTS. Open-labeled, randomized study. The effects of two supplements, Nokogiriyashi EX ® containing 160 mg saw palmetto (SP) extract per tablet and Edicare ® containing 10 mg of Pycnogenol ® , 115 mg of l-arginine and 92 mg of aspartate (PAA) per tablet on International Prostate Symptom Score (IPSS), IPSS-QOL, Overactive Bladder Symptom Score (OABSS), International Index of Erectile Function 5 (IIEF5), Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), urinary 8-OHdG and uroflowmetry (UFM) of total 40 men with LUTS and SDys were examined. 19 subjects were instructed to take two tablets of SP, on the other 20 were on four tablets of PAA for 16 weeks. IPSS and IPSS-QOL showed statistically significant improvements in both groups. OABSS and IIEF5 were significantly improved in the PAA group. Conversely, ICIQ-SF, 8-OHdG and UFM did not change in either group. PAA might be an effective therapeutic alternative for elderly patients with LUTS and SDys.

  9. L-arginine availability and arginase activity: Characterization of amino acid permease 3 in Leishmania amazonensis.

    PubMed

    Aoki, Juliana Ide; Muxel, Sandra Marcia; Zampieri, Ricardo Andrade; Acuña, Stephanie Maia; Fernandes, Juliane Cristina Ribeiro; Vanderlinde, Rubia Heloisa; Sales, Maria Carmen Oliveira de Pinho; Floeter-Winter, Lucile Maria

    2017-10-01

    its decrease in L-arginine supplementation. The differential AAP3 expression was determined in the differentiation of promastigotes to amastigotes conditions, as well as the detection of AAP3 in the plasma membrane reflecting in the L-arginine uptake. Our data suggest that depending on the amino acid pool and arginase activity, Leishmania senses and could use an alternative route for the amino acid transport in response to stress signaling.

  10. L-arginine availability and arginase activity: Characterization of amino acid permease 3 in Leishmania amazonensis

    PubMed Central

    Aoki, Juliana Ide; Muxel, Sandra Marcia; Zampieri, Ricardo Andrade; Acuña, Stephanie Maia; Fernandes, Juliane Cristina Ribeiro; Vanderlinde, Rubia Heloisa; Sales, Maria Carmen Oliveira de Pinho

    2017-01-01

    also showed the increased AAP3 levels under amino acid starvation or its decrease in L-arginine supplementation. The differential AAP3 expression was determined in the differentiation of promastigotes to amastigotes conditions, as well as the detection of AAP3 in the plasma membrane reflecting in the L-arginine uptake. Our data suggest that depending on the amino acid pool and arginase activity, Leishmania senses and could use an alternative route for the amino acid transport in response to stress signaling. PMID:29073150

  11. Role of L-arginine in the pathogenesis and treatment of renal disease.

    PubMed

    Cherla, Gautam; Jaimes, Edgar A

    2004-10-01

    L-arginine is a semi essential amino acid and also a substrate for the synthesis of nitric oxide (NO), polyamines, and agmatine. These L-arginine metabolites may participate in the pathogenesis of renal disease and constitute the rationale for manipulating L-arginine metabolism as a strategy to ameliorate kidney disease. Modification of dietary L-arginine intake in experimental models of kidney diseases has been shown to have both beneficial as well as deleterious effects depending on the specific model studied. L-arginine supplementation in animal models of glomerulonephritis has been shown to be detrimental, probably by increasing the production of NO from increased local expression of inducible NO synthase (iNOS). L-arginine supplementation does not modify the course of renal disease in humans with chronic glomerular diseases. However, beneficial effects of L-arginine supplementation have been reported in several models of chronic kidney disease including renal ablation, ureteral obstruction, nephropathy secondary to diabetes, and salt-sensitive hypertension. L-arginine is reduced in preeclampsia and recent experimental studies indicate that L-arginine supplementation may be beneficial in attenuating the symptoms of preeclampsia. Administration of exogenous L-arginine has been shown to be protective in ischemic acute renal failure. In summary, the role of L-arginine in the pathogenesis and treatment of renal disease is not completely understood and remains to be established.

  12. REM sleep deprivation induces endothelial dysfunction and hypertension in middle-aged rats: Roles of the eNOS/NO/cGMP pathway and supplementation with L-arginine.

    PubMed

    Jiang, Jiaye; Gan, Zhongyuan; Li, Yuan; Zhao, Wenqi; Li, Hanqing; Zheng, Jian-Pu; Ke, Yan

    2017-01-01

    Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes. The results showed that REM sleep deprivation decreased body weight, increased blood pressure, and impaired endothelial function of the aortas in middle-aged rats but not young rats. Moreover, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) concentrations as well as endothelial NO synthase (eNOS) phosphorylation in the aorta were decreased by REM sleep deprivation. Supplementation with L-arginine could protect against REM sleep deprivation-induced hypertension, endothelial dysfunction, and damage to the eNOS/NO/cGMP signaling pathway. The results of the present study suggested that REM sleep deprivation caused endothelial dysfunction and hypertension in middle-aged rats via the eNOS/NO/cGMP pathway and that these pathological changes could be inhibited via L-arginine supplementation. The present study provides a new strategy to inhibit the signaling pathways involved in insomnia-induced or insomnia-enhanced cardiovascular diseases.

  13. Year-long changes in protein metabolism in elderly men and women supplemented with a nutrition cocktail of beta-hydroxy-beta-methylbutyrate (HMB), L-arginine, and L-lysine.

    PubMed

    Baier, Shawn; Johannsen, Darcy; Abumrad, Naji; Rathmacher, John A; Nissen, Steven; Flakoll, Paul

    2009-01-01

    A major contributing factor to the loss of mobility in elderly people is the gradual and continuous loss of lean body mass. To determine whether supplementation of an amino acid cocktail daily for 1 year could improve the age-associated changes in protein turnover and lean body mass in elderly people. Elderly (76+/-1.6 years) women (n=39) and men (n=38) were recruited for a double-blinded controlled study. Study participants were randomly assigned to either an isonitrogenous control-supplement (n=37) or a treatment-supplement (HMB/Arg/Lys) consisting of beta-hydroxy-beta-methylbutyrate, L-arginine, and L-lysine (n=40) for the 1-year study. Lean tissue mass was measured using both bioelectrical-impedance analysis (BIA) and dual energy x-ray absorptiometry (DXA). Rates of whole-body protein turnover were estimated using primed/intermittent oral doses of 15N-glycine. In subjects taking the HMB/Arg/Lys supplement, lean tissue increased over the year of study while in the control group, lean tissue did not change. Compared with control, HMB/Arg/Lys increased body cell mass (BIA) by 1.6% (P=.002) and lean mass (DXA) by 1.2% (P=.05). The rates of protein turnover were significantly increased 8% and 12% in the HMB/Arg/Lys-supplemented group while rates of protein turnover decreased 11% and 9% in the control-supplemented subjects (P<.01), at 3 and 12 months, respectively. Consumption of a simple amino acid-related cocktail increased protein turnover and lean tissue in elderly individuals in a year-long study.

  14. l-Arginine is a Radioprotector for Hematopoietic Progenitor Cells

    PubMed Central

    Pearce, Linda L.; Zheng, Xichen; Martinez-Bosch, Sandra; Kerr, Patrick P.; Khlangwiset, Pornsri; Epperly, Michael W.; Fink, Mitchell P.; Greenberger, Joel S.; Peterson, Jim

    2012-01-01

    l-Arginine is shown to protect hematopoietic progenitor (32D cl 3) cells from death due to exposure to γ radiation (137Cs). Some of the other intermediates in the urea cycle, namely ornithine and citrulline, plus urea itself, were not found to have any significant impact on cell survival after irradiation. Intriguingly, supplementation of irradiated cells with l-arginine results in decreased production of peroxynitrite, suggesting that suppression of superoxide generation by nitric oxide synthase in one or more microenvironments is an important factor in the observed radioprotection. The absence of any radioprotective effect of l-arginine in cells at 3% oxygen also confirms the involvement of one or more oxygen-derived species. Knockdown experiments with nitric oxide synthase (NOS) siRNAs in cells and NOS knockout animals confirm that the observed radioprotection is associated with nNOS (NOS-1). l-Arginine also ameliorates the transient inhibition of the electron-transport chain complex I that occurs within 30 min of completing the dose (10 Gy) and that appears to be a functional marker for postirradiation mitochondrial oxidant production. PMID:22175298

  15. Plasma L-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction.

    PubMed

    Sandqvist, Anna; Schneede, Jörn; Kylhammar, David; Henrohn, Dan; Lundgren, Jakob; Hedeland, Mikael; Bondesson, Ulf; Rådegran, Göran; Wikström, Gerhard

    2018-03-01

    Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from L-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, L-arginine, L-ornithine, and L-citrulline were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma levels of ADMA and SDMA were higher, whereas L-arginine and L-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of L-arginine than patients with LVSD (p < 0.05). L-Arginine correlated to 6 min walking distance (6MWD) (r s  = 0.58, p = 0.006) and L-arginine/ADMA correlated to WHO functional class (r s  = -0.46, p = 0.043) in PAH. In conclusion, L-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, L-arginine correlated with 6MWD in PAH. L-arginine may provide useful information in differentiating PAH from LVSD.

  16. Diminished L-arginine bioavailability in hypertension.

    PubMed

    Moss, Monique B; Brunini, Tatiana M C; Soares De Moura, Roberto; Novaes Malagris, Lúcia E; Roberts, Norman B; Ellory, J Clive; Mann, Giovanni E; Mendes Ribeiro, Antônio C

    2004-10-01

    L-Arginine is the precursor of NO (nitric oxide), a key endogenous mediator involved in endothelium-dependent vascular relaxation and platelet function. Although the concentration of intracellular L-arginine is well above the Km for NO synthesis, in many cells and pathological conditions the transport of L-arginine is essential for NO production (L-arginine paradox). The present study was designed to investigate the modulation of L-arginine/NO pathway in systemic arterial hypertension. Transport of L-arginine into RBCs (red blood cells) and platelets, NOS (NO synthase) activity and amino acid profiles in plasma were analysed in hypertensive patients and in an animal model of hypertension. Influx of L-arginine into RBCs was mediated by the cationic amino acid transport systems y+ and y+L, whereas, in platelets, influx was mediated only via system y+L. Chromatographic analyses revealed higher plasma levels of L-arginine in hypertensive patients (175+/-19 micromol/l) compared with control subjects (137+/-8 micromol/l). L-Arginine transport via system y+L, but not y+, was significantly reduced in RBCs from hypertensive patients (60+/-7 micromol.l(-1).cells(-1).h(-1); n=16) compared with controls (90+/-17 micromol.l(-1).cells(-1).h(-1); n=18). In human platelets, the Vmax for L-arginine transport via system y+L was 86+/-17 pmol.10(9) cells(-1).min(-1) in controls compared with 36+/-9 pmol.10(9) cells(-1).min(-1) in hypertensive patients (n=10; P<0.05). Basal NOS activity was decreased in platelets from hypertensive patients (0.12+/-0.02 pmol/10(8) cells; n=8) compared with controls (0.22+/-0.01 pmol/10(8) cells; n=8; P<0.05). Studies with spontaneously hypertensive rats demonstrated that transport of L-arginine via system y+L was also inhibited in RBCs. Our findings provide the first evidence that hypertension is associated with an inhibition of L-arginine transport via system y+L in both humans and animals, with reduced availability of L-arginine limiting NO synthesis

  17. Dietary supplementation with L-arginine or N-carbamylglutamate enhances intestinal growth and heat shock protein-70 expression in weanling pigs fed a corn- and soybean meal-based diet.

    PubMed

    Wu, Xin; Ruan, Zheng; Gao, Yunling; Yin, Yulong; Zhou, Xihong; Wang, Lei; Geng, Meimei; Hou, Yongqing; Wu, Guoyao

    2010-08-01

    This study determined effects of dietary supplementation with L-arginine (Arg) or N-carbamylglutamate (NCG) on intestinal health and growth in early-weaned pigs. Eighty-four Landrace x Yorkshire pigs (average body weight of 5.56+/-0.07 kg; weaned at 21 days of age) were fed for 7 days one of the three isonitrogenous diets: (1) a corn- and soybean meal-based diet (CSM), (2) CSM+0.08% NCG (0.08%), and (3) CSM+0.6% Arg. There were four pens of pigs per diet (7 pigs/pen). At the end of a 7-day feeding period, six piglets were randomly selected from each treatment for tissue collections. Compared with the control group, Arg or NCG supplementation increased (P<0.05): (1) Arg concentrations in plasma, (2) small-intestinal growth, (3) villus height in duodenum, jejunum and ileum, (4) crypt depth in jejunum and ileum, (5) goblet cell counts in intestinal mucosae, and (6) whole-body weight gain in pigs. Real-time polymerase chain reaction and western blotting analyses revealed that both mRNA and protein levels for heat shock protein-70 (HSP70) were higher (P<0.05) in the intestinal mucosae of Arg- or NCG-supplemented pigs than in the control group. Furthermore, the incidence of diarrhea in the NCG group was 18% lower (P<0.01) than that in the control group. Collectively, these results indicate that dietary supplementation with 0.6% Arg or 0.08% NCG enhances intestinal HSP70 gene expression, intestinal growth and integrity, and the availability of dietary nutrients for whole-body weight gain in postweaning pigs fed a CSM-based diet. Thus, Arg or NCG is a functional ingredient in the weaning diet to improve nutrition, health, and growth performance of these neonates.

  18. L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice.

    PubMed

    Aji, W; Ravalli, S; Szabolcs, M; Jiang, X C; Sciacca, R R; Michler, R E; Cannon, P J

    1997-01-21

    The potential antiatherosclerotic actions of NO were investigated in four groups of mice (n = 10 per group) lacking functional LDL receptor genes, an animal model of familial hypercholesterolemia. Group 1 was fed a regular chow diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition, group 3 received supplemental L-arginine and group 4 received L-arginine and N omega-nitro-L-arginine (L-NA), an inhibitor of NO synthase (NOS). Animals were killed at 6 months; aortas were stained with oil red O for planimetry and with antibodies against constitutive and inducible NOSs. Plasma cholesterol was markedly increased in the animals receiving the high-cholesterol diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receiving L-arginine. Aortic atherosclerosis was present in all mice on the high-cholesterol diet. The mean atherosclerotic lesion area was reduced significantly (P < .01) in the cholesterol-fed mice given L-arginine compared with those receiving the high-cholesterol diet alone. The mean atherosclerotic lesion area was significantly larger (P < .01) in cholesterol-fed mice receiving L-arginine + L-NA than in those on the high-cholesterol diet alone. Within the atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for inducible NOS and nitrotyrosine residues. The data indicate that L-arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor knockout mice fed a high-cholesterol diet. The abrogation of the beneficial effects of L-arginine by L-NA suggests that the antiatherosclerotic actions of L-arginine are mediated by NOS. The data suggest that L-arginine may be beneficial in familial hypercholesterolemia.

  19. Intracellular L-arginine concentration does not determine NO production in endothelial cells: Implications on the 'L-arginine paradox'

    SciTech Connect

    Shin, Soyoung; Mohan, Srinidi; Fung, Ho-Leung, E-mail: hlfung@buffalo.edu

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer Our findings provide a possible solution to the 'L-arginine paradox'. Black-Right-Pointing-Pointer Extracellular L-arginine concentration is the major determinant of NO production. Black-Right-Pointing-Pointer Cellular L-arginine action is limited by cellular ARG transport, not the K{sub m} of NOS. Black-Right-Pointing-Pointer We explain how L-arginine supplementation can work to increase endothelial function. -- Abstract: We examined the relative contributory roles of extracellular vs. intracellular L-arginine (ARG) toward cellular activation of endothelial nitric oxide synthase (eNOS) in human endothelial cells. EA.hy926 human endothelial cells were incubated with different concentrations of {sup 15}N{sub 4}-ARG, ARG, or L-arginine ethyl ester (ARG-EE) for 2 h.more » To modulate ARG transport, siRNA for ARG transporter (CAT-1) vs. sham siRNA were transfected into cells. ARG transport activity was assessed by cellular fluxes of ARG, {sup 15}N{sub 4}-ARG, dimethylarginines, and L-citrulline by an LC-MS/MS assay. eNOS activity was determined by nitrite/nitrate accumulation, either via a fluorometric assay or by{sup 15}N-nitrite or estimated {sup 15}N{sub 3}-citrulline concentrations when {sup 15}N{sub 4}-ARG was used to challenge the cells. We found that ARG-EE incubation increased cellular ARG concentration but no increase in nitrite/nitrate was observed, while ARG incubation increased both cellular ARG concentration and nitrite accumulation. Cellular nitrite/nitrate production did not correlate with cellular total ARG concentration. Reduced {sup 15}N{sub 4}-ARG cellular uptake in CAT-1 siRNA transfected cells vs. control was accompanied by reduced eNOS activity, as determined by {sup 15}N-nitrite, total nitrite and {sup 15}N{sub 3}-citrulline formation. Our data suggest that extracellular ARG, not intracellular ARG, is the major determinant of NO production in endothelial cells. It is likely that once transported inside

  20. Effect of L-arginine on the growth of Plasmodium falciparum and immune modulation of host cells.

    PubMed

    Awasthi, Vikky; Chauhan, Rubika; Chattopadhyay, Debprasad; Das, Jyoti

    2017-01-01

    Malaria is a life-threatening disease caused by Plasmodium parasites. The life-cycle of Plasmodium species involves several stages both in mosquito and the vertebrate host. In the erythrocytic stage, Plasmodium resides inside the red blood cells (RBCs), where it meets most of its nutritional requirement by degrad- ing host's haemoglobin. L-arginine is required for growth and division of cells. The present study was aimed to demonstrate the effect of supplementation of different concentrations of L-arginine and L-citrulline on the growth of parasite, and effect of the culture supernatant on the host's peripheral blood mononuclear cells (PBMCs). To examine the effect of supplementation of L-arginine and L-citrulline, Plasmodium falciparum (3D7 strain) was cultured in RPMI 1640, L-arginine deficient RPMI 1640, and in different concentrations of L-arginine, and L-citrulline supplemented in arginine deficient RPMI 1640 medium. To have a holistic view of in vivo cell activation, the PBMCs isolated from healthy human host were cultured in the supernatant collected from P. falciparum culture. Growth of the parasite was greatly enhanced in L-arginine supplemented media and was found to be concentration dependent. However, parasite growth was compromised in L-citrulline supplemented and L-arginine deficient media. The supernatant collected from L-arginine supplemented parasite media (sArg) showed increased FOXP3 and interleukin-10 (IL-10) expression as compared to the supernatant collected from L-citrulline supple- mented parasite media (sCit). The in vitro culture results showed, decreased parasite growth, and decreased expression of programmed cell death-1 (PD-1) (a coinhibitory molecule) and IL-10 in the L-citrulline supplemented media as compared to L-arginine supplemented media. Hence, it was concluded that L-citrulline supplementation would be a better alternative than L-arginine to inhibit the parasite growth.

  1. Serum Amino Acids Profile and the Beneficial Effects of L-Arginine or L-Glutamine Supplementation in Dextran Sulfate Sodium Colitis

    PubMed Central

    Wu, Miaomiao; Liu, Gang; Yang, Guan; Xion, Yan; Su, Dingding; Wu, Li; Li, Tiejun; Chen, Shuai; Duan, Jielin; Yin, Yulong; Wu, Guoyao

    2014-01-01

    This study was conducted to investigate serum amino acids profile in dextran sulfate sodium (DSS)-induced colitis, and impacts of graded dose of arginine or glutamine supplementation on the colitis. Using DSS-induced colitis model, which is similar to human ulcerative colitis, we determined serum profile of amino acids at day 3, 7, 10 and 12 (5 days post DSS treatment). Meanwhile, effects of graded dose of arginine (0.4%, 0.8%, and 1.5%) or glutamine (0.5%, 1.0% and 2.0%) supplementation on clinical parameters, serum amino acids, colonic tight junction proteins, colonic anti-oxidative indicators [catalase, total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px)], colonic pro-inflammatory cytokines [interleukin-1 beta (IL-1β), IL-6, IL-17 and tumor necrosis factor alpha (TNF-α)] in DSS-induced colitis were fully analyzed at day 7 and 12. Additionally, the activation of signal transduction pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK), phosphoinositide-3-kinases (PI3K)/PI3K-protein kinase B (Akt), and myosin light chain kinase (MLCK)- myosin light chain (MLC20), were analyzed using immunoblotting. Serum amino acids analysis showed that DSS treatment changed the serum contents of amino acids, such as Trp, Glu, and Gln (P<0.05). Dietary arginine or glutamine supplementation had significant (P<0.05) influence on the clinical and biochemical parameters (T-SOD, IL-17 and TNF-α) in colitis model. These results were associated with colonic NF-κB, PI3K-Akt and MLCK signaling pathways. In conclusion, arginine or glutamine could be a potential therapy for intestinal inflammatory diseases. PMID:24505477

  2. Serum amino acids profile and the beneficial effects of L-arginine or L-glutamine supplementation in dextran sulfate sodium colitis.

    PubMed

    Ren, Wenkai; Yin, Jie; Wu, Miaomiao; Liu, Gang; Yang, Guan; Xion, Yan; Su, Dingding; Wu, Li; Li, Tiejun; Chen, Shuai; Duan, Jielin; Yin, Yulong; Wu, Guoyao

    2014-01-01

    This study was conducted to investigate serum amino acids profile in dextran sulfate sodium (DSS)-induced colitis, and impacts of graded dose of arginine or glutamine supplementation on the colitis. Using DSS-induced colitis model, which is similar to human ulcerative colitis, we determined serum profile of amino acids at day 3, 7, 10 and 12 (5 days post DSS treatment). Meanwhile, effects of graded dose of arginine (0.4%, 0.8%, and 1.5%) or glutamine (0.5%, 1.0% and 2.0%) supplementation on clinical parameters, serum amino acids, colonic tight junction proteins, colonic anti-oxidative indicators [catalase, total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px)], colonic pro-inflammatory cytokines [interleukin-1 beta (IL-1β), IL-6, IL-17 and tumor necrosis factor alpha (TNF-α)] in DSS-induced colitis were fully analyzed at day 7 and 12. Additionally, the activation of signal transduction pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPK), phosphoinositide-3-kinases (PI3K)/PI3K-protein kinase B (Akt), and myosin light chain kinase (MLCK)-myosin light chain (MLC20), were analyzed using immunoblotting. Serum amino acids analysis showed that DSS treatment changed the serum contents of amino acids, such as Trp, Glu, and Gln (P<0.05). Dietary arginine or glutamine supplementation had significant (P<0.05) influence on the clinical and biochemical parameters (T-SOD, IL-17 and TNF-α) in colitis model. These results were associated with colonic NF-κB, PI3K-Akt and MLCK signaling pathways. In conclusion, arginine or glutamine could be a potential therapy for intestinal inflammatory diseases.

  3. L-arginine enhances cell proliferation and reduces apoptosis in human endometrial RL95-2 cells

    USDA-ARS?s Scientific Manuscript database

    L-arginine is considered to be one of the most versatile amino acids due to the fact that it serves as a precursor for many important molecules in cellular physiology. When supplemented in the diet, L-arginine can increase the number of implantation sites in mice and rats, suggesting an effect at th...

  4. Kidney Mass Reduction Leads to l-Arginine Metabolism-Dependent Blood Pressure Increase in Mice.

    PubMed

    Pillai, Samyuktha Muralidharan; Seebeck, Petra; Fingerhut, Ralph; Huang, Ji; Ming, Xiu-Fen; Yang, Zhihong; Verrey, François

    2018-02-25

    Uninephrectomy (UNX) is performed for various reasons, including kidney cancer or donation. Kidneys being the main site of l-arginine production in the body, we tested whether UNX mediated kidney mass reduction impacts l-arginine metabolism and thereby nitric oxide production and blood pressure regulation in mice. In a first series of experiments, we observed a significant increase in arterial blood pressure 8 days post-UNX in female and not in male mice. Further experimental series were performed in female mice, and the blood pressure increase was confirmed by telemetry. l-citrulline, that is used in the kidney to produce l-arginine, was elevated post-UNX as was also asymmetric dimethylarginine, an inhibitor of nitric oxide synthase that competes with l-arginine and is a marker for renal failure. Interestingly, the UNX-induced blood pressure increase was prevented by supplementation of the diet with 5% of the l-arginine precursor, l-citrulline. Because l-arginine is metabolized in the kidney and other peripheral tissues by arginase-2, we tested whether the lack of this metabolic pathway also compensates for decreased l-arginine production in the kidney and/or for local nitric oxide synthase inhibition and consecutive blood pressure increase. Indeed, upon uninephrectomy, arginase-2 knockout mice (Arg-2 -/- ) neither displayed an increase in asymmetric dimethylarginine and l-citrulline plasma levels nor a significant increase in blood pressure. UNX leads to a small increase in blood pressure that is prevented by l-citrulline supplementation or arginase deficiency, 2 measures that appear to compensate for the impact of kidney mass reduction on l-arginine metabolism. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  5. L-Arginine promotes protein synthesis and cell growth in brown adipocyte precursor cells via the mTOR signal pathway.

    PubMed

    Ma, Xi; Han, Meng; Li, Defa; Hu, Shengdi; Gilbreath, Kyler R; Bazer, Fuller W; Wu, Guoyao

    2017-05-01

    L-Arginine has been reported to enhance brown adipose tissue developments in fetal lambs of obese ewes, but the underlying mechanism is unknown. The present study tested the hypothesis that L-arginine stimulates growth and development of brown adipocyte precursor cells (BAPCs) through activation of mammalian target of rapamycin cell signaling. BAPCs isolated from fetal lambs at day 90 of gestation were incubated   for 6 h in arginine-free DMEM, and then cultured in DMEM with concentrations of 50, 100, 200, 500 or 1000 μmol L-arginine/L for 24-96 h. Cell proliferation, protein turnover, the mammalian target of rapamycin (mTOR) signaling pathway and pre-adipocyte differentiation markers were determined. L-arginine treatment enhanced (P < 0.05) BAPC growth and protein synthesis, while inhibiting proteolysis in a dose-dependent manner. Compared with 50 and 100 μmol/L (the concentrations of arginine in the maternal plasma of obese ewes), 200 μmol L-arginine/L (the concentrations of arginine in the maternal plasma of obese ewes receiving arginine supplementation) increased (P < 0.05) the abundances of phosphorylated mTOR, P70 S6K and 4EBP1, as well as the abundances of PGC1α, UCP1, BMP7 and PRDM16. These novel findings indicate that increasing extra-cellular arginine concentration from 50 to 200 µmol/L activates mTOR cell signaling in BAPCs and enhances their growth and development in a dose-dependent manner. Our results provide a mechanism for arginine supplementation to enhance the development of brown adipose tissue in fetal lambs.

  6. Oral L-arginine before resistance exercise blunts growth hormone in strength trained males.

    PubMed

    Forbes, Scott C; Harber, Vicki; Bell, Gordon J

    2014-04-01

    Acute resistance exercise and L-arginine have both been shown to independently elevate plasma growth hormone (GH) concentrations; however, their combined effect is controversial. The purpose was to investigate the combined effects of resistance exercise and L-arginine supplementation on plasma L-arginine, GH, GH secretagogues, and IGF-1 in strength trained participants. Fourteen strength trained males (age: 25 ± 4 y; body mass: 81.4 ± 9.0 kg; height: 179.4 ± 6.9 cm; and training experience: 6.3 ± 3.4 y) participated in a randomized double-blind crossover design (separated by ~7 days). Subjects reported to the laboratory at 08:00 in a fasted state, consumed L-arginine (ARG; 0.075 g·kg-1 body mass) or a placebo (PLA) before performing an acute bout of resistance exercise (3 sets of 8 exercises, 10 repetitions at ~75% 1RM). Blood samples were collected at rest, before exercise, and at 0, 15, 30, and 60 min of rest-recovery. The ARG condition significantly increased plasma L-arginine concentrations (~120%) while no change was detected in the PLA condition. There were no differences between conditions for GH, GH-releasing hormone, ghrelin, or IGF-1 at any time point. GH-inhibiting hormone was significantly lower in the ARG condition. However, integrated area under the curve for GH was blunted in the ARG condition (L-arginine = 288.4 ± 368.7 vs. placebo = 487.9± 482.0 min·ng·mL1, p < .05). L-arginine ingested before resistance exercise significantly elevated plasma L-arginine concentration but attenuated plasma GH in strength trained individuals despite a lower GHIH. Furthermore our data shows that the GH suppression was not due to a GH or IGF-1 induced autonegative feedback loop.

  7. L-Arginine Modulates Glucose and Lipid Metabolism in Obesity and Diabetes.

    PubMed

    Hu, Shengdi; Han, Meng; Rezaei, Arash; Li, Defa; Wu, Guoyao; Ma, Xi

    2017-01-01

    Type 2 diabetes has become a global public health problem affecting approximately 380 million people throughout the world. It can cause many complications and lead to greater mortality. At present, there is no available medicine for effectively preventing diabetes. L-arginine, a functional amino acid, the precursor of nitric oxide, plays a crucial role in maintenance, reproduction, growth, anti-aging and immunity for animals. Growing clinical evidence indicates that dietary L-arginine supplementation can reduce obesity, decrease arterial blood pressure, resist oxidation and normalize endothelial dysfunction to bring about remission of type 2 diabetes. The potential molecular mechanism may play a role in modulating glucose homeostasis, promoting lipolysis, maintaining hormone levels, ameliorating insulin resistance, and fetal programing in early stages. The possible signaling pathway of the beneficial effects of L-arginine likely involves L-arginine-nitric oxide pathway through which cell signal protein can be activated. Accumulating studies have indicated that L-arginine may have potential to prevent and/or relieve type 2 diabetes via restoring insulin sensitivity in vivo. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Malate and Aspartate Increase L-Arginine and Nitric Oxide and Attenuate Hypertension.

    PubMed

    Hou, Entai; Sun, Na; Zhang, Fuchang; Zhao, Chenyang; Usa, Kristie; Liang, Mingyu; Tian, Zhongmin

    2017-05-23

    Fumarase catalyzes the interconversion of fumarate and L-malate in the tricarboxylic acid cycle. The Dahl salt-sensitive (SS) rat, a model of salt-sensitive hypertension, exhibits fumarase insufficiencies. To investigate the mechanism mediating the effect of fumarase-related metabolites on hypertension, we considered the pathway in which L-malate can be converted to oxaloacetate, aspartate, argininosuccinate, and L-arginine, the substrate of nitric oxide (NO) synthase. The levels of aspartate, citrulline, L-arginine, and NO were significantly decreased in the kidneys of SS rats compared to salt-insensitive consomic SS.13 BN rats. Knockdown of fumarase in human kidney cells and vascular endothelial cells resulted in decreased levels of malate, aspartate, L-arginine, and NO. Supplementation of aspartate or malate increased renal levels of L-arginine and NO and attenuated hypertension in SS rats. These findings reveal a multi-step metabolic pathway important for hypertension in which malate and aspartate may modulate blood pressure by altering levels of L-arginine and NO. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. The second case of a young man with L-arginine-induced acute pancreatitis.

    PubMed

    Binet, Quentin; Dufour, Inès; Agneessens, Emmanuel; Debongnie, Jean-Claude; Aouattah, Tarik; Covas, Angélique; Coche, Jean-Charles; De Koninck, Xavier

    2018-04-21

    Dietary supplementation of arginine has been used by numerous world-class athletes and professional bodybuilders over the past 30 years. L-Arginine indeed enhances muscular power and general performance via maintaining ATP level. However, L-arginine is also known to induce acute pancreatitis in murine models. We report the case of young man presenting with upper abdominal pain and increased serum lipase levels. Contrast-enhanced computed tomography confirms a mild acute pancreatitis. Common etiologies have been ruled out and toxicological anamnestic screening reveals the intake of protein powder. This is, to the best of our knowledge, the second case in human of arginine-induced acute pancreatitis. This case report suggests that every patient presenting with acute pancreatitis without obvious etiology should be evaluated for the intake of toxics other than alcohol, including L-arginine.

  10. L-arginine: a new opportunity in the management of clinical derangements in dialysis patients.

    PubMed

    Bellinghieri, Guido; Santoro, Domenico; Mallamace, Agostino; Di Giorgio, Rosa Maria; De Luca, Grazia; Savica, Vincenzo

    2006-07-01

    L-Arginine is an essential amino acid for infants and growing children, as well as for pregnant women. This amino acid is a substrate for at least 5 enzymes identified in mammals, including arginase, arginine-glycine transaminase, kyotorphine synthase, nitric oxide synthase, and arginine decarboxylase. L-arginine is essential for the synthesis of creatine, urea, polyamines, nitric oxide, and agmatine. Arginine may be considered an essential amino acid in sepsis, and its supplementation could be beneficial in this clinical setting by improving microcirculation and protein anabolism. Rats receiving arginine-supplemented parenteral nutrition showed an increased ability to synthesize acute phase proteins when challenged with sepsis. Finally, L-arginine exerts antihypertensive and antiproliferative effects on vascular smooth muscles. It has been shown to reduce systemic blood pressure in some forms of experimental hypertension. Endothelial dysfunction and reduced nitric oxide bioactivity are associated with increased incidence of cardiovascular diseases. A beneficial effect of acute and chronic L-arginine supplementation on endothelial derived nitric oxide production and endothelial function has been shown. In end-stage renal disease patients, the rate of de novo arginine synthesis seemed to be preserved. Our preliminary data on a group of dialysis patients showed that predialysis arginine levels were stable in a normal range during the dialysis session and that hypertensive patients had lower arginine-citrulline ratio than normotensive patients.

  11. Neurodevelopmental outcomes of premature infants treated with l-arginine for prevention of necrotising enterocolitis.

    PubMed

    Amin, Harish J; Soraisham, Amuchou S; Sauve, Reg S

    2009-04-01

    This study aimed to compare the long-term neurodevelopmental outcomes at 36 months adjusted age in preterm infants (birth weight < or = 1250 gm) who received supplementation with L-arginine during the first 28 days of life with controls. Surviving infants enrolled in a randomised control study of L-arginine supplementation were prospectively followed longitudinally to determine their neurodevelopmental outcomes at 36 months of adjusted age. Neurologic examination and neurodevelopmental assessments were performed by examiners who were unaware of the original treatment assignments. A total of 132 children (95% of survivors) were evaluated at 36 months adjusted age. In the group given L-arginine, 5 of 61 (8.1%) had major neurodevelopmental disabilities, defined as the presence of one or more of cerebral palsy, cognitive delay (cognitive index <70), bilateral blindness or bilateral hearing loss requiring hearing aids as compared with 9 of 71 (12.6%) in the placebo group (relative risk, 0.64; 95 % confidence interval, 0.22-1.82; P= 0.40). There is no increase in neurodevelopmental disability in preterm infants who received L-arginine supplementation.

  12. l-Arginine induces antioxidant response to prevent oxidative stress via stimulation of glutathione synthesis and activation of Nrf2 pathway.

    PubMed

    Liang, Mingcai; Wang, Zhengxuan; Li, Hui; Cai, Liang; Pan, Jianghao; He, Hongjuan; Wu, Qiong; Tang, Yinzhao; Ma, Jiapei; Yang, Lin

    2018-05-01

    Arginine is a conditionally essential amino acid. To elucidate the influence of l-arginine on the activation of endogenous antioxidant defence, male Wistar rats were orally administered daily with l-arginine at different levels of 25, 50, 100 mg/100 g body weight. After 7 and 14 days feeding, the antioxidative capacities and glutathione (GSH) contents in the plasma and in the liver were uniformly enhanced with the increasing consumption of l-arginine, whereas the oxidative stress was effectively suppressed by l-arginine treatment. After 14 days feeding, the mRNA levels and protein expressions of Keap1 and Cul3 were gradually reduced by increasing l-arginine intake, resulting that the nuclear factor Nrf2 was activated. Upon activation of Nrf2, the expressions of antioxidant responsive element (ARE)-dependent genes and proteins (GCLC, GCLM, GS, GR, GST, GPx, CAT, SOD, NQO1, HO-1) were up-regulated by l-arginine feeding, indicating an upward trend in antioxidant capacity uniformly with the increasing consumption of l-arginine. The present study demonstrates that the supplementation of l-arginine stimulates GSH synthesis and activates Nrf2 pathway, leading to the up-regulation of ARE-driven antioxidant expressions via Nrf2-Keap1 pathway. Results suggest the availability of l-arginine is a critical factor to suppress oxidative stress and induce an endogenous antioxidant response. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. l-Arginine-Dependent Epigenetic Regulation of Interleukin-10, but Not Transforming Growth Factor-β, Production by Neonatal Regulatory T Lymphocytes

    PubMed Central

    Yu, Hong-Ren; Tsai, Ching-Chang; Chang, Ling-Sai; Huang, Hsin-Chun; Cheng, Hsin-Hsin; Wang, Jiu-Yao; Sheen, Jiunn-Ming; Kuo, Ho-Chang; Hsieh, Kai-Sheng; Huang, Ying-Hsien; Yang, Kuender D.; Hsu, Te-Yao

    2017-01-01

    A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency. PMID:28487700

  14. Effect of L-arginine and sildenafil citrate on intrauterine growth restriction fetuses: a meta-analysis.

    PubMed

    Chen, Juncao; Gong, Xiaoyuan; Chen, Pingyang; Luo, Kaiju; Zhang, Xiuquan

    2016-08-16

    Intrauterine growth restriction (IUGR) is associated with perinatal morbidity and mortality. Several clinical trials have reported L-arginine and sildenafil citrate had effect on intrauterine growth restriction fetuses. A meta-analysis of available randomized controlled trials (RCTs) was conducted to investigate the effects of L-arginine and sildenafil citrate on major clinical outcomes of IUGR fetuses. Systematically searched Medline, Embase, the Cochrane Library, and Clinical Trials, references of retrieved articles, and conference proceedings from 1960 to 2015. We included randomized controlled trials assessing the effects of L-arginine and sildenafil citrate on IUGR. Outcomes analyzed were the birth weight, gestational age at labor, Apgar score at 1and 5 min, the ratio of NRDS, the ratio of ICH and neonatal death, etc. Ten trials were included. Nine trials (576 patients) compared L-arginine with either placebo or no intervention. In the L-arginine treatment groups of the L-arginine trials, there was a significant increase in fetal birth weight (SMD 0.41, 95 % CI [0.24,0.58]), gestational age (SMD 0.30, 95 % CI [0.07,0.54]); L-arginine treatment group have a significant reduction in the ratio of neonatal respiratory distress syndrome (P = 0.009), intracranial hemorrhage of fetuses (P = 0.002), but the number of included studies and people on these outcomes are small. As only one trial (41 patients) compared sildenafil citrate with placebo, it was too small for reliable conclusions about possible differential effects could be drawn. The results of this meta-analysis showed that L-arginine increased birth weight and prolonged gestational age at labor of IUGR fetuses. However, further large-scale RCTs are needed to adequately assess the effect of L-arginine and Sildenafil citrate on clinical outcomes, because the number of study may be small.

  15. L-Arginine and Alzheimer's Disease

    PubMed Central

    Yi, Jing; Horky, Laura L.; Friedlich, Avi L.; Shi, Ying; Rogers, Jack T.; Huang, Xudong

    2009-01-01

    Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive neurodegeneration and loss of cognitive and memory functions. Although the exact causes of AD are still unclear, evidence suggests that atherosclerosis, redox stress, inflammation, neurotransmitter dysregulation, and impaired brain energy metabolism may all be associated with AD pathogenesis. Herein, we explore a possible role for L-arginine (L-arg) in AD, taking into consideration known functions for L-arg in atherosclerosis, redox stress and the inflammatory process, regulation of synaptic plasticity and neurogenesis, and modulation of glucose metabolism and insulin activity. L-arg, a precursor of nitric oxide and polyamine, exhibits multiple functions in human health and may play a prominent role in age-related degenerative diseases such as AD. PMID:19079617

  16. Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling

    PubMed Central

    Xiong, Yuyani; Fru, Michael Forbiteh; Yu, Yi; Montani, Jean-Pierre; Ming, Xiu-Fen; Yang, Zhihong

    2014-01-01

    L-arginine supplementation is proposed to improve health status or as adjunct therapy for diseases including cardiovascular diseases. However, controversial results and even detrimental effects of L-arginine supplementation are reported. We investigate potential mechanisms of L-arginine-induced detrimental effects on vascular endothelial cells. Human endothelial cells were exposed to a physiological (0.1 mmol/L) or pharmacological (0.5 mmol/L) concentration of L-arginine for 30 minutes (acute) or 7 days (chronic). The effects of L-arginine supplementation on endothelial senescence phenotype, i.e., levels of senescence-associated beta-galactosidase, expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1, eNOS-uncoupling, arginase-II expression/activity, and mTORC1-S6K1 activity were analyzed. While acute L-arginine treatment enhances endothelial NO production accompanied with superoxide production and activation of S6K1 but no up-regulation of arginase-II, chronic L-arginine supplementation causes endothelial senescence, up-regulation of the adhesion molecule expression, and eNOS-uncoupling (decreased NO and enhanced superoxide production), which are associated with S6K1 activation and up-regulation of arginase-II. Silencing either S6K1 or arginase-II inhibits up-regulation/activation of each other, prevents endothelial dysfunction, adhesion molecule expression, and senescence under the chronic L-arginine supplementation condition. These results demonstrate that S6K1 and arginase-II form a positive circuit mediating the detrimental effects of chronic L-arginine supplementation on endothelial cells. PMID:24860943

  17. Metabolic engineering of Corynebacterium glutamicum for L-arginine production.

    PubMed

    Park, Seok Hyun; Kim, Hyun Uk; Kim, Tae Yong; Park, Jun Seok; Kim, Suok-Su; Lee, Sang Yup

    2014-08-05

    L-arginine is an important amino acid for diverse industrial and health product applications. Here we report the development of metabolically engineered Corynebacterium glutamicum ATCC 21831 for the production of L-arginine. Random mutagenesis is first performed to increase the tolerance of C. glutamicum to L-arginine analogues, followed by systems metabolic engineering for further strain improvement, involving removal of regulatory repressors of arginine operon, optimization of NADPH level, disruption of L-glutamate exporter to increase L-arginine precursor and flux optimization of rate-limiting L-arginine biosynthetic reactions. Fed-batch fermentation of the final strain in 5 l and large-scale 1,500 l bioreactors allows production of 92.5 and 81.2 g l(-1) of L-arginine with the yields of 0.40 and 0.35 g L-arginine per gram carbon source (glucose plus sucrose), respectively. The systems metabolic engineering strategy described here will be useful for engineering Corynebacteria strains for the industrial production of L-arginine and related products.

  18. ORAL DELIVERY OF L-ARGININE STIMULATES PROSTAGLANDIN-DEPENDENT SECRETORY DIARRHEA IN C. PARVUM INFECTED NEONATAL PIGLETS

    PubMed Central

    Gookin, Jody L.; Foster, Derek M.; Coccaro, Maria R.; Stauffer, Stephen H.

    2008-01-01

    Objectives To determine if oral supplementation with L-arginine could augment nitric oxide (NO) synthesis and promote epithelial defense in neonatal piglets infected with C. parvum. Methods Neonatal piglets were fed a liquid milk replacer and on day 3 of age infected or not with 108 C. parvum oocysts and the milk replacer supplemented with L-arginine or L-alanine. Milk consumption, body weight, fecal consistency, and oocyst excretion were recorded daily. On day 3 post-infection, piglets were euthanized, and serum concentration of NO metabolites and histological severity of villous atrophy and epithelial infection were quantified. Sheets of ileal mucosa were mounted in Ussing chambers for measurement of barrier function (transepithelial resistance (TER) and permeability) and short-circuit current (Isc; an indirect measurement of Cl− secretion in this tissue). Results C. parvum infected piglets had large numbers of epithelial parasites, villous atrophy, decreased barrier function, severe watery diarrhea, and failure to gain weight. L-arginine promoted synthesis of NO by infected piglets which was unaccompanied by improvement in severity of infection but rather promoted epithelial chloride secretion and diarrhea. Epithelial secretion by infected mucosa from L-arginine supplemented piglets was fully inhibited by the cyclooxygenase inhibitor indomethacin, indicating that prostaglandin synthesis was responsible for this effect. Conclusions Results of these studies demonstrate that provision of additional NO substrate in the form of L-arginine incites prostaglandin-dependent secretory diarrhea and does not promote epithelial defense or barrier function of C. parvum infected neonatal ileum. PMID:18223372

  19. Tetrahydrobiopterin, l-Arginine and Vitamin C Act Synergistically to Decrease Oxidant Stress and Increase Nitric Oxide That Increases Blood Flow Recovery after Hindlimb Ischemia in the Rat

    PubMed Central

    Yan, Jinglian; Tie, Guodong; Messina, Louis M

    2012-01-01

    Nitric oxide (NO) derived from endothelial nitric oxide synthase (eNOS) is a potent vasodilator and signaling molecule that plays essential roles in neovascularization. During limb ischemia, decreased NO bioavailability occurs secondary to increased oxidant stress, decreased l-arginine and tetrahydrobiopterin. This study tested the hypothesis that dietary cosupplementation with tetrahydrobiopterin (BH4), l-arginine and vitamin C acts synergistically to decrease oxidant stress, increase NO and thereby increase blood flow recovery after hindlimb ischemia. Rats were fed normal chow, chow supplemented with BH4 or l-arginine (alone or in combination) or chow supplemented with BH4 + l-arginine + vitamin C for 1 wk before induction of hindlimb ischemia. In the is-chemic hindlimb, cosupplementation with BH4 + l-arginine resulted in greater eNOS and phospho-eNOS (P-eNOS) expression, Ca2+-dependent NOS activity and NO concentration in the ischemic calf region (gastrocnemius), as well as greater NO concentration in the region of collateral arteries (gracilis). Rats receiving cosupplementation of BH4 + l-arginine led to greater recovery of foot perfusion and greater collateral enlargement than did rats receiving either agent separately. The addition of vitamin C to the BH4 + l-arginine regimen further increased these dependent variables. In addition, rats given all three supplements showed significantly less Ca2+-independent activity, less nitrotyrosine accumulation, greater glutathione (GSH)–to–glutathione disulfide (GSSG) ratio and less gastrocnemius muscle necrosis, on both macroscopic and microscopic levels. In conclusion, co-supplementation with BH4 + l-arginine + vitamin C significantly increased blood flow recovery after hindlimb ischemia by reducing oxidant stress, increasing NO bioavailability, enlarging collateral arteries and reducing muscle necrosis. Oral cosupplementation of BH4, l-arginine and vitamin C holds promise as a biological therapy to induce

  20. Fluorometric enzymatic assay of L-arginine

    NASA Astrophysics Data System (ADS)

    Stasyuk, Nataliya; Gayda, Galina; Yepremyan, Hasmik; Stepien, Agnieszka; Gonchar, Mykhailo

    2017-01-01

    The enzymes of L-arginine (further - Arg) metabolism are promising tools for elaboration of selective methods for quantitative Arg analysis. In our study we propose an enzymatic method for Arg assay based on fluorometric monitoring of ammonia, a final product of Arg splitting by human liver arginase I (further - arginase), isolated from the recombinant yeast strain, and commercial urease. The selective analysis of ammonia (at 415 nm under excitation at 360 nm) is based on reaction with o-phthalaldehyde (OPA) in the presence of sulfite in alkali medium: these conditions permit to avoid the reaction of OPA with any amino acid. A linearity range of the fluorometric arginase-urease-OPA method is from 100 nM to 6 μМ with a limit of detection of 34 nM Arg. The method was used for the quantitative determination of Arg in the pooled sample of blood serum. The obtained results proved to be in a good correlation with the reference enzymatic method and literature data. The proposed arginase-urease-OPA method being sensitive, economical, selective and suitable for both routine and micro-volume formats, can be used in clinical diagnostics for the simultaneous determination of Arg as well as urea and ammonia in serum samples.

  1. Comparative Proteomics Analysis Reveals L-Arginine Activates Ethanol Degradation Pathways in HepG2 Cells.

    PubMed

    Yan, Guokai; Lestari, Retno; Long, Baisheng; Fan, Qiwen; Wang, Zhichang; Guo, Xiaozhen; Yu, Jie; Hu, Jun; Yang, Xingya; Chen, Changqing; Liu, Lu; Li, Xiuzhi; Purnomoadi, Agung; Achmadi, Joelal; Yan, Xianghua

    2016-03-17

    L-Arginine (Arg) is a versatile amino acid that plays crucial roles in a wide range of physiological and pathological processes. In this study, to investigate the alteration induced by Arg supplementation in proteome scale, isobaric tags for relative and absolute quantification (iTRAQ) based proteomic approach was employed to comparatively characterize the differentially expressed proteins between Arg deprivation (Ctrl) and Arg supplementation (+Arg) treated human liver hepatocellular carcinoma (HepG2) cells. A total of 21 proteins were identified as differentially expressed proteins and these 21 proteins were all up-regulated by Arg supplementation. Six amino acid metabolism-related proteins, mostly metabolic enzymes, showed differential expressions. Intriguingly, Ingenuity Pathway Analysis (IPA) based pathway analysis suggested that the three ethanol degradation pathways were significantly altered between Ctrl and +Arg. Western blotting and enzymatic activity assays validated that the key enzymes ADH1C, ALDH1A1, and ALDH2, which are mainly involved in ethanol degradation pathways, were highly differentially expressed, and activated between Ctrl and +Arg in HepG2 cells. Furthermore, 10 mM Arg significantly attenuated the cytotoxicity induced by 100 mM ethanol treatment (P < 0.0001). This study is the first time to reveal that Arg activates ethanol degradation pathways in HepG2 cells.

  2. Dietary l-arginine inhibits intestinal Clostridium perfringens colonisation and attenuates intestinal mucosal injury in broiler chickens.

    PubMed

    Zhang, Beibei; Lv, Zengpeng; Li, Huixian; Guo, Shuangshuang; Liu, Dan; Guo, Yuming

    2017-09-01

    We investigated the effects of dietary l-arginine level and feeding duration on the intestinal damage of broilers induced by Clostridium perfringens (CP) in vivo, and the antimicrobial effect of its metabolite nitric oxide (NO) in vitro. The in vivo experiment was designed as a factorial arrangement of three dietary treatments×two challenge statuses. Broilers were fed a basal diet (CON) or a high-arginine diet (ARG) containing 1·87 % l-arginine, or CON for the first 8 d and ARG from days 9 to 28 (CON/ARG). Birds were co-infected with or without Eimeria and CP (EM/CP). EM/CP challenge led to intestinal injury, as evidenced by lower plasma d-xylose concentration (P<0·01), higher paracellular permeability in the ileum (P<0·05) and higher numbers of Escherichia coli (P<0·05) and CP (P<0·001) in caecal digesta; however, this situation could be alleviated by l-arginine supplementation (P<0·05). The intestinal claudin-1 and occludin mRNA expression levels were decreased (P<0·05) following EM/CP challenge; this was reversed by l-arginine supplementation (P<0·05). Moreover, EM/CP challenge up-regulated (P<0·05) claudin-2, interferon-γ (IFN-γ), toll-like receptor 2 and nucleotide-binding oligomerisation domain 1 (NOD1) mRNA expression, and l-arginine supplementation elevated (P<0·05) IFN-γ, IL-10 and NOD1 mRNA expression. In vitro study showed that NO had bacteriostatic activity against CP (P<0·001). In conclusion, l-arginine supplementation could inhibit CP overgrowth and alleviate intestinal mucosal injury by modulating innate immune responses, enhancing barrier function and producing NO.

  3. Effects of N-acetylcysteine and L-arginine in the antioxidant system of C2C12 cells.

    PubMed

    Da Silva, E P; Lambertucci, R H

    2015-06-01

    The aim of this study was to evaluate the effects of N-acetylcysteine or L-arginine in the antioxidant system of skeletal muscle cells in culture. We used C2C12 cells which were supplemented or not with N-acetylcysteine or L-arginine at different time points. Antioxidant enzymes' activities and protein expression were evaluated. Additionally, superoxide production by cytochrome c reduction method was carried out. It was observed that the supplementation with either N-acetylcysteine or L-arginine was capable to acutely reduce superoxide production (after 30 and 60 minutes). Surprisingly, N-acetylcysteine supplementation also induced an increased production of superoxide during the period of 24 hours. Moreover, both supplements were capable to improve the activity and protein expression of some antioxidants enzymes. In conclusion, we have found new evidences showing that N-acetylcysteine or L-arginine supplementation can provide some benefits to the antioxidant system of skeletal muscle cells in culture. Further studies have to be carried out to evaluate if such benefits could also occur in an in vivo model, with possible benefits for athletes' health and performance.

  4. Maintenance of cytosolic calcium is crucial to extend l-arginine therapeutic benefits during continuous dosing.

    PubMed

    Mohan, Srinidi; Harding, Lisa

    2016-10-01

    The therapeutic benefits associated with short-term l-arginine supplementation are lost during continuous dosing. AMP-activated protein kinase (AMPK) functional modulation has been correlated with l-arginine therapeutic effectiveness, and with tolerance development during continuous supplementation. However, the metabolic link that is responsible for AMPK functional modulation during continuous l-arginine exposure is currently not known. To explore this, we incubated HUVECs for 7 days with 100 μmol/L l-arginine, in the presence or absence of other agents; and monitored their effects for eNOS function, and on tolerance sparing effects (viz, cellular glucose accumulation, and oxidative stress). HUVEC co-incubation with 100 μmol/L l-arginine and ≤1200 mg/mL calcium (Ca 2+ ) for 7 days avoided tolerance development, with an at least 1-fold increase in the eNOS and AMPK functional activity; and an 1-fold increase in overall cellular glucose uptake. The overall cellular cytosolic Ca 2+ was below 200 nmol/L, with no change in cellular glucose and superoxide/peroxynitrite (O 2 •- /ONOO - ) level from control. However, tolerance sparing effects of at least 70% decrease in eNOS and AMPK functional response, with an 1-fold reduction in glucose uptake, and at least 2-fold increase in O 2 •- /ONOO - were observed in cells exposed for 7 days to 100 μmol/L l-arginine at Ca 2+ co-incubation concentration of >1200 mg/mL. The >1200 mg/mL Ca2+ co-incubation condition, also improved the overall cellular Ca 2+ to >200 nmol/L. Similar tolerance response was observed in cells co-treated with 100 μmol/L l-arginine and ≤1200 mg/mL Ca 2+ in the presence of Ca 2+ influx inhibitor (20 μmol/L 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid), or eNOS activity inhibitor (30 μmol/L l-N G -nitroarginine methyl ester). No tolerance response was seen in cells incubated for 7 days with 100 μmol/L l-arginine and ≤1200 mg/mL Ca 2+ ; even in the presence of the inhibitor for

  5. L-arginine reverses alterations in drug disposition induced by spinal cord injury by increasing hepatic blood flow.

    PubMed

    Vertiz-Hernandez, Antonio; Castaneda-Hernandez, Gilberto; Martinez-Cruz, Angelina; Cruz-Antonio, Leticia; Grijalva, Israel; Guizar-Sahagun, Gabriel

    2007-12-01

    High hepatic extraction drugs--such as phenacetin, methylprednisolone, and cyclosporine--exhibit an increased bioavailability after acute spinal cord injury (SCI) due to an impaired clearance. For these drugs, metabolic clearance depends on hepatic blood flow. Thus, it is possible that pharmacokinetic alterations can be reversed by increasing liver perfusion. Therefore, we evaluated the effect of L-arginine, a nitric oxide precursor, on the pharmacokinetics of a prototype drug with high hepatic extraction, and on hepatic microvascular blood flow (MVBF) after acute SCI. Pharmacokinetics of i.v. phenacetin was studied in rats 24 h after a severe T-5 spinal cord contusion; animals being pretreated with L-arginine 100 mg/kg i.v. or vehicle. MVBF was assessed under similar experimental conditions using laser Doppler flowmetry. SCI significantly altered phenacetin pharmacokinetics. Clearance was significantly reduced, resulting in a prolonged half-life and an increase in bioavailability, while volume of distribution was decreased. Pharmacokinetic alterations were reversed when injured rats were pretreated with L -arginine. It was also observed that L-arginine significantly increased hepatic MVBF in injured rats, notwithstanding it exhibited a limited effect on sham-injured animals. Our data hence suggest that L-arginine is able to reverse SCI-induced alterations in phenacetin pharmacokinetics due to an impaired hepatic MVBF, likely by increased nitric oxide synthesis leading to vasodilation. Further studies are warranted to examine the potential usefulness of nitric oxide supplementation in a clinical setting.

  6. L-arginine and Vitamin D Adjunctive Therapies in Pulmonary Tuberculosis: A Randomised, Double-Blind, Placebo-Controlled Trial

    PubMed Central

    Ralph, Anna P.; Waramori, Govert; Pontororing, Gysje J.; Kenangalem, Enny; Wiguna, Andri; Tjitra, Emiliana; Sandjaja; Lolong, Dina B.; Yeo, Tsin W.; Chatfield, Mark D.; Soemanto, Retno K.; Bastian, Ivan; Lumb, Richard; Maguire, Graeme P.; Eisman, John; Price, Ric N.; Morris, Peter S.; Kelly, Paul M.; Anstey, Nicholas M.

    2013-01-01

    Background Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). Methods In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339. Results 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference −3%, 95% CI −19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI −9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. Conclusion Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained

  7. L-arginine and vitamin D adjunctive therapies in pulmonary tuberculosis: a randomised, double-blind, placebo-controlled trial.

    PubMed

    Ralph, Anna P; Waramori, Govert; Pontororing, Gysje J; Kenangalem, Enny; Wiguna, Andri; Tjitra, Emiliana; Sandjaja; Lolong, Dina B; Yeo, Tsin W; Chatfield, Mark D; Soemanto, Retno K; Bastian, Ivan; Lumb, Richard; Maguire, Graeme P; Eisman, John; Price, Ric N; Morris, Peter S; Kelly, Paul M; Anstey, Nicholas M

    2013-01-01

    Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339. 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference -3%, 95% CI -19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI -9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained, affected TB outcomes. Clinical

  8. Influence of L-arginine during bovine in vitro fertilization.

    PubMed

    Silva, Thiago Velasco Guimarães; da Silva, Bruno Baraúna; de Sá, André Luiz Alves; da Costa, Nathalia Nogueira; Sampaio, Rafael Vilar; Cordeiro, Marcela da Silva; Santana, Priscila Di Paula Bessa; Adona, Paulo Roberto; Santos, Simone do Socorro Damasceno; Miranda, Moysés dos Santos; Ohashi, Otávio Mitio

    2014-12-01

    The objective of this work was to evaluate the effect of using L-arginine during in vitro fertilization (IVF) on in vitro embryonic development using Bos taurus and Bos indicus semen. Effect of different concentrations (0, 1, 10 and 50 mM) of L-arginine, added to the IVF medium, was evaluated on the fertilization rate at 18 h post-fertilization (hpf), NO3(-)/NO2(-) production during IVF by the Griess colorimetric method (30 hpf), cleavage and blastocyst rates (on Day 2 and Day 7 of culture, respectively) and total blastocyst cell number (Day 7 of culture). The results reveal that the addition of 50 mM L-arginine to IVF medium, with either Bos taurus or Bos indicus spermatozoa, decreased the cleavage rate and blastocyst rate compared to the control group. Other concentrations did not affect embryo production. However, 1 mM L-arginine with Bos indicus semen increased the proportion of hatched blastocysts. These results indicate that high L-arginine concentrations may exhibit toxic effects on bovine gametes during in vitro fertilization.

  9. Rabbit aortic endothelial dysfunction by low-density lipoprotein is attenuated by L-arginine, L-ascorbate and pyridoxine

    PubMed Central

    Ji, Yong; Han, Yi; Diao, Jianxin; Huang, Yan; Chen, Qi; Ferro, Albert

    2003-01-01

    We investigated the relative effectiveness of L-arginine, L-ascorbate and pyridoxine in preventing the impairment of endothelium-mediated vasorelaxation induced by native low-density lipoprotein (nLDL) from healthy subjects, oxidised LDL (oxLDL, formed by oxidation of nLDL) or nLDL from type II diabetic patients (dLDL). Rabbit aortic rings were exposed to nLDL, dLDL or oxLDL (50–200 mg protein l−1), or corresponding vehicle, following which they were constricted with noradrenaline 10−6 M; concentration–relaxation curves were determined to acetylcholine (ACh), A23187, or sodium nitroprusside (NP), in the absence or presence of L-arginine (10−5–10−3 M), L-ascorbate (10−5–10−3 M) and pyridoxine (0.5–2.0 mM). nLDL, dLDL and oxLDL all inhibited relaxant responses to ACh and A23187, but not to NP, in a concentration-dependent manner (oxLDL>dLDL>nLDL). In the presence of all LDL preparations, L-arginine, L-ascorbate or pyridoxine each improved ACh and A23187 responses, although none completely normalised endothelium-dependent relaxations. The maximal effect of L-arginine occurred at 10−4 M. The combination of L-arginine 10−4 M, L-ascorbate 10−5 M and pyridoxine 2.0 mM was equally effective as L-arginine 10−4 M alone. Our results confirm that nLDL, dLDL and oxLDL exert inhibitory effects on endothelium dependent, but not endothelium independent, relaxation of rabbit aorta. ACh and A23187 responses in the presence of any LDL species can be ameliorated by supplementation with L-arginine, L-ascorbate or pyridoxine, either singly or in combination, with no agent or combination proving superior to L-arginine alone. Nevertheless, ACh and A23187 responses are not completely normalised with such supplements, suggesting that there also exists a component of LDL-induced inhibition of endothelium-mediated vasorelaxation that is independent of the nitric oxide system. PMID:14597596

  10. Taste Perception of Sweet, Sour, Salty, Bitter, and Umami and Changes Due to l-Arginine Supplementation, as a Function of Genetic Ability to Taste 6-n-Propylthiouracil.

    PubMed

    Melis, Melania; Tomassini Barbarossa, Iole

    2017-05-25

    Behavioral reaction to different taste qualities affects nutritional status and health. 6- n -Propylthiouracil (PROP) tasting has been reported to be a marker of variation in taste perception, food preferences, and eating behavior, but results have been inconsistent. We showed that l-Arg can enhance the bitterness intensity of PROP, whilst others have demonstrated a suppression of the bitterness of quinine. Here, we analyze the taste perception of sweet, sour, salty, bitter, and umami and the modifications caused by l-Arg supplementation, as a function of PROP-taster status. Taste perception was assessed by testing the ability to recognize, and the responsiveness to, representative solutions of the five primary taste qualities, also when supplemented with l-Arg, in subjects classified as PROP-tasting. Super-tasters, who showed high papilla density, gave higher ratings to sucrose, citric acid, caffeine, and monosodium l-glutamate than non-tasters. l-Arg supplementation mainly modified sucrose perception, enhanced the umami taste, increased NaCl saltiness and caffeine bitterness only in tasters, and decreased citric acid sourness. Our findings confirm the role of PROP phenotype in the taste perception of sweet, sour, and bitter and show its role in umami. The results suggest that l-Arg could be used as a strategic tool to specifically modify taste responses related to eating behaviors.

  11. Taste Perception of Sweet, Sour, Salty, Bitter, and Umami and Changes Due to l-Arginine Supplementation, as a Function of Genetic Ability to Taste 6-n-Propylthiouracil

    PubMed Central

    Melis, Melania; Tomassini Barbarossa, Iole

    2017-01-01

    Behavioral reaction to different taste qualities affects nutritional status and health. 6-n-Propylthiouracil (PROP) tasting has been reported to be a marker of variation in taste perception, food preferences, and eating behavior, but results have been inconsistent. We showed that l-Arg can enhance the bitterness intensity of PROP, whilst others have demonstrated a suppression of the bitterness of quinine. Here, we analyze the taste perception of sweet, sour, salty, bitter, and umami and the modifications caused by l-Arg supplementation, as a function of PROP-taster status. Taste perception was assessed by testing the ability to recognize, and the responsiveness to, representative solutions of the five primary taste qualities, also when supplemented with l-Arg, in subjects classified as PROP-tasting. Super-tasters, who showed high papilla density, gave higher ratings to sucrose, citric acid, caffeine, and monosodium l-glutamate than non-tasters. l-Arg supplementation mainly modified sucrose perception, enhanced the umami taste, increased NaCl saltiness and caffeine bitterness only in tasters, and decreased citric acid sourness. Our findings confirm the role of PROP phenotype in the taste perception of sweet, sour, and bitter and show its role in umami. The results suggest that l-Arg could be used as a strategic tool to specifically modify taste responses related to eating behaviors. PMID:28587069

  12. Prevention of muscle fibers atrophy during gravitational unloading: The effect of L-arginine administration

    NASA Astrophysics Data System (ADS)

    Kartashkina, N.; Lomonosova, Y.; Shevchenko, T. F.; Bugrova, A. E.; Turtikova, O. V.; Kalamkarov, G. R.; Nemirovskaya, T. L.

    2011-05-01

    Gravitational unloading results in pronounced atrophy of m.soleus. Probably, the output of NO is controlled by the muscle activity. We hypothesized that NO may be involved in the protein metabolism and increase of its concentration in muscle can prevent atrophic changes induced by gravitational unloading. In order to test the hypothesis we applied NO donor L-arginine during gravitational unloading. 2.5-month-old male Wistar rats weighing 220-230g were divided into sedentary control group (CTR, n=7), 14-day hindlimb suspension (HS, n=7), 14 days of hindlimb suspension+ L-arginine (HSL, n=7) (with a daily supplementation of 500 mg/kg wt L-arginine) and 14 days of hindlimb suspension+ L-NAME (HSN, n=7) (90 mg/kg wt during 14 days). Cross sectional area (CSA) of slow twitch (ST) and fast twitch (FT) soleus muscle fibers decreased by 45% and 28% in the HS group ( p<0.05) and 40% and 25% in the HSN group, as compared to the CTR group ( p<0.05), respectively. CSA of ST and FT muscle fibers were 25% and 16% larger in the HSL group in comparison with the HS group ( p<0.05), respectively. The atrophy of FT muscle fibers in the HSL group was completely prevented since FT fiber CSA had no significant differences from the CTR group. In HS group, the percentage of fibers revealing either gaps/disruption of the dystrophin layer of the myofiber surface membrane increased by 27% and 17%, respectively, as compared to the controls (CTR group, p<0.05). The destructions in dystrophin layer integrity and reductions of desmin content were significantly prevented in HSL group. NO concentration decreased by 60% in the HS group (as well as HSN group) and at the same time no changes were detectable in the HSL group. This fact indicates the compensation of NO content in the unloaded muscle under L-arginine administration. The levels of atrogin-1 mRNA were considerably altered in suspended animals (HS group: plus 27%, HSL group: minus 13%) as compared to the control level. Conclusion: L-arginine

  13. Arginase Inhibition Restores Peroxynitrite-Induced Endothelial Dysfunction via L-Arginine-Dependent Endothelial Nitric Oxide Synthase Phosphorylation

    PubMed Central

    Nguyen, Minh Cong; Park, Jong Taek; Jeon, Yeong Gwan; Jeon, Byeong Hwa; Hoe, Kwang Lae; Kim, Young Myeong

    2016-01-01

    Purpose Peroxynitrite plays a critical role in vascular pathophysiology by increasing arginase activity and decreasing endothelial nitric oxide synthase (eNOS) activity. Therefore, the aims of this study were to investigate whether arginase inhibition and L-arginine supplement could restore peroxynitrite-induced endothelial dysfunction and determine the involved mechanism. Materials and Methods Human umbilical vein endothelial cells (HUVECs) were treated with SIN-1, a peroxynitrite generator, and arginase activity, nitrite/nitrate production, and expression levels of proteins were measured. eNOS activation was evaluated via Western blot and dimer blot analysis. We also tested nitric oxide (NO) and reactive oxygen species (ROS) production and performed a vascular tension assay. Results SIN-1 treatment increased arginase activity in a time- and dose-dependent manner and reciprocally decreased nitrite/nitrate production that was prevented by peroxynitrite scavenger in HUVECs. Furthermore, SIN-1 induced an increase in the expression level of arginase I and II, though not in eNOS protein. The decreased eNOS phosphorylation at Ser1177 and the increased at Thr495 by SIN-1 were restored with arginase inhibitor and L-arginine. The changed eNOS phosphorylation was consistent in the stability of eNOS dimers. SIN-1 decreased NO production and increased ROS generation in the aortic endothelium, all of which was reversed by arginase inhibitor or L-arginine. NG-Nitro-L-arginine methyl ester (L-NAME) prevented SIN-1-induced ROS generation. In the vascular tension assay, SIN-1 enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxant responses to acetylcholine that were reversed by arginase inhibition. Conclusion These findings may explain the beneficial effect of arginase inhibition and L-arginine supplement on endothelial dysfunction under redox imbalance-dependent pathophysiological conditions. PMID:27593859

  14. Arginase Inhibition Restores Peroxynitrite-Induced Endothelial Dysfunction via L-Arginine-Dependent Endothelial Nitric Oxide Synthase Phosphorylation.

    PubMed

    Nguyen, Minh Cong; Park, Jong Taek; Jeon, Yeong Gwan; Jeon, Byeong Hwa; Hoe, Kwang Lae; Kim, Young Myeong; Lim, Hyun Kyo; Ryoo, Sungwoo

    2016-11-01

    Peroxynitrite plays a critical role in vascular pathophysiology by increasing arginase activity and decreasing endothelial nitric oxide synthase (eNOS) activity. Therefore, the aims of this study were to investigate whether arginase inhibition and L-arginine supplement could restore peroxynitrite-induced endothelial dysfunction and determine the involved mechanism. Human umbilical vein endothelial cells (HUVECs) were treated with SIN-1, a peroxynitrite generator, and arginase activity, nitrite/nitrate production, and expression levels of proteins were measured. eNOS activation was evaluated via Western blot and dimer blot analysis. We also tested nitric oxide (NO) and reactive oxygen species (ROS) production and performed a vascular tension assay. SIN-1 treatment increased arginase activity in a time- and dose-dependent manner and reciprocally decreased nitrite/nitrate production that was prevented by peroxynitrite scavenger in HUVECs. Furthermore, SIN-1 induced an increase in the expression level of arginase I and II, though not in eNOS protein. The decreased eNOS phosphorylation at Ser1177 and the increased at Thr495 by SIN-1 were restored with arginase inhibitor and L-arginine. The changed eNOS phosphorylation was consistent in the stability of eNOS dimers. SIN-1 decreased NO production and increased ROS generation in the aortic endothelium, all of which was reversed by arginase inhibitor or L-arginine. N(G)-Nitro-L-arginine methyl ester (L-NAME) prevented SIN-1-induced ROS generation. In the vascular tension assay, SIN-1 enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxant responses to acetylcholine that were reversed by arginase inhibition. These findings may explain the beneficial effect of arginase inhibition and L-arginine supplement on endothelial dysfunction under redox imbalance-dependent pathophysiological conditions.

  15. l-Arginine administration attenuates airway inflammation by altering l-arginine metabolism in an NC/Nga mouse model of asthma.

    PubMed

    Zhang, Ran; Kubo, Masayuki; Murakami, Ikuo; Setiawan, Heri; Takemoto, Kei; Inoue, Kiyomi; Fujikura, Yoshihisa; Ogino, Keiki

    2015-05-01

    Changes in l-arginine metabolism, including increased arginase levels and decreased nitric oxide production, are involved in the pathophysiology of asthma. In this study, using an intranasal mite-induced NC/Nga mouse model of asthma, we examined whether administration of l-arginine ameliorated airway hyperresponsiveness and inflammation by altering l-arginine metabolism. Experimental asthma was induced in NC/Nga mice via intranasal administration of mite crude extract (50 µg/day) on 5 consecutive days (days 0-4, sensitization) and on day 11 (challenge). Oral administration of l-arginine (250 mg/kg) was performed twice daily on days 5-10 for prevention or on days 11-13 for therapy. On day 14, we evaluated the inflammatory airway response (airway hyperresponsiveness, the number of cells in the bronchoalveolar lavage fluid, and the changes in pathological inflammation of the lung), arginase expression and activity, l-arginine bioavailability, and the concentration of NOx, the end products of nitric oxide. Treatment with l-arginine ameliorated the mite-induced inflammatory airway response. Furthermore, l-arginine administration attenuated the increases in arginase expression and activity and elevated the NOx levels by enhancing l-arginine bioavailability. These findings indicate that l-arginine administration may contribute to the improvement of asthmatic symptoms by altering l-arginine metabolism.

  16. Effects of long-term losartan and L-arginine treatment on haemodynamics, glomerular filtration, and SOD activity in spontaneously hypertensive rats.

    PubMed

    Miloradović, Zoran; Jovović, Durdica; Mihailović-Stanojević, Nevena; Milanović, Jelica Grujić; Milanović, Sladan

    2008-04-01

    Recently, it has been reported that losartan, an angiotensin II receptor (ATR) antagonist, depresses the angiotensin II-induced production of superoxide radicals. Also, in spontaneously hypertensive rats (SHR) endothelial dysfunction is associated with decreased nitric oxide (NO) synthesis. In this study, we examined the effects of long-term ATR blockade and L-arginine supplementation on the haemodynamic parameters, glomerular filtration, and oxidative status in SHR. Adult male SHR were treated with losartan (10 mg/kg) and with the NO donor L-arginine (2 g/kg) for 4 weeks. The animals were divided into the following experimental groups: control (n = 7), L-arginine (n = 7), losartan (n = 7), and L-arginine + losartan (n = 7). Mean arterial pressure (MAP), regional blood flow, urea clearance, and activity of superoxide dismutase (SOD) were measured at the end of treatment. MAP was significantly reduced in the losartan group compared with the control group (133.3 +/- 7.3 vs. 161.5 +/- 14.5 mm Hg). Aortic blood flow was significantly higher and aortic vascular resistance was significantly lower in all treated groups than in the control. Urea clearance rose significantly in the L-arginine + losartan group compared with control (393.27 +/- 37.58 vs. 218.68 +/- 42.03 microL x min(-1) x 100 g(-1)) as did the activity of SOD (1668.97 +/- 244.57 vs. 1083.18 +/- 169.96 U/g Hb). Our results suggest that the antihypertensive effect of losartan and L-arginine in SHR is not primarily mediated by increased SOD activity. Also, combined treatment with ATR blockade and L-arginine supplementation has a beneficial effect on renal function that is, at least in part, mediated by increased SOD activity in SHR.

  17. L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats.

    PubMed

    Ramprasath, Tharmarajan; Kumar, Palani Hamenth; Puhari, Shanavas Syed Mohamed; Murugan, Ponniah Senthil; Vasudevan, Varadaraj; Selvam, Govindan Sadasivam

    2012-11-23

    Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg(-1) body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-κB. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic and control rats. Under these findings, we suggest that targeting of eNOS and Nrf2 signaling by L-arginine supplementation could be used as a potential treatment method to alleviate the late diabetic complications. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. [l-arginine efficiency in MELAS syndrome. A case report].

    PubMed

    Moutaouakil, F; El Otmani, H; Fadel, H; Sefrioui, F; Slassi, I

    2009-05-01

    Mitochondrial encephalomyopathy lactic acidosis and stoke-like episodes (MELAS) is a rare neurodegenerative disease caused by mutations of mitochondrial DNA. We report the case of a 12-year-old child with MELAS syndrome who presented with recurrent migraine-like headache and sudden blindness suggesting stroke-like episodes. Furthermore, he developed progressive muscular impairment with bilateral hearing loss. Serum lactate and pyruvate levels were elevated and the muscle biopsy showed an aspect of red-ragged fibers with Gomori trichrome. Brain imaging showed calcifications of basal ganglia on the CT scan and a parieto-occipital high signal on diffusion-weighted MRI. A genetic analysis was not performed but the presence of hearing loss in the patient's mother was suggestive of maternal transmission. Stroke-like episodes in the form of migraine-like headache and blindness were the patient's major complaint and did not improve despite analgesic drugs. After oral administration of l-arginine at the dose of 0.4mg/kg per day, stroke-like symptoms totally and rapidly disappeared. The efficiency of l-arginine in stroke-like episodes was initially reported then confirmed in a controlled study. The pathophysiology of stoke-like episodes and the mechanisms underlying the action of l-arginine are discussed.

  19. L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

    SciTech Connect

    Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer L-Arginine treatment reduced the metabolic disturbances in diabetic animals. Black-Right-Pointing-Pointer Antioxidant marker proteins were found high in myocardium by L-arginine treatment. Black-Right-Pointing-Pointer Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. Black-Right-Pointing-Pointer L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. Black-Right-Pointing-Pointer Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-argininemore » supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg{sup -1} body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-{kappa}B. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from

  20. Improvement of the ammonia assimilation for enhancing L-arginine production of Corynebacterium crenatum.

    PubMed

    Guo, Jing; Man, Zaiwei; Rao, Zhiming; Xu, Meijuan; Yang, Taowei; Zhang, Xian; Xu, Zhenghong

    2017-03-01

    There are four nitrogen atoms in L-arginine molecule and the nitrogen content is 32.1%. By now, metabolic engineering for L-arginine production strain improvement was focused on carbon flux optimization. In previous work, we obtained an L-arginine-producing Corynebacterium crenatum SDNN403 (ARG) through screening and mutation breeding. In this paper, a strain engineering strategy focusing on nitrogen supply and ammonium assimilation for L-arginine production was performed. Firstly, the effects of nitrogen atom donor (L-glutamate, L-glutamine and L-aspartate) addition on L-arginine production of ARG were studied, and the addition of L-glutamine and L-aspartate was beneficial for L-arginine production. Then, the glutamine synthetase gene glnA and aspartase gene aspA from E. coli were overexpressed in ARG for increasing the L-glutamine and L-aspartate synthesis, and the L-arginine production was effectively increased. In addition, the L-glutamate supply re-emerged as a limiting factor for L-arginine biosynthesis. Finally, the glutamate dehydrogenase gene gdh was co-overexpressed for further enhancement of L-arginine production. The final strain could produce 53.2 g l -1 of L-arginine, which was increased by 41.5% compared to ARG in fed-batch fermentation.

  1. Malaria-Associated l-Arginine Deficiency Induces Mast Cell-Associated Disruption to Intestinal Barrier Defenses against Nontyphoidal Salmonella Bacteremia

    PubMed Central

    Chau, Jennifer Y.; Tiffany, Caitlin M.; Nimishakavi, Shilpa; Lawrence, Jessica A.; Pakpour, Nazzy; Mooney, Jason P.; Lokken, Kristen L.; Caughey, George H.; Tsolis, Renee M.

    2013-01-01

    Coinfection with malaria and nontyphoidal Salmonella serotypes (NTS) can cause life-threatening bacteremia in humans. Coinfection with malaria is a recognized risk factor for invasive NTS, suggesting that malaria impairs intestinal barrier function. Here, we investigated mechanisms and strategies for prevention of coinfection pathology in a mouse model. Our findings reveal that malarial-parasite-infected mice, like humans, develop l-arginine deficiency, which is associated with intestinal mastocytosis, elevated levels of histamine, and enhanced intestinal permeability. Prevention or reversal of l-arginine deficiency blunts mastocytosis in ileal villi as well as bacterial translocation, measured as numbers of mesenteric lymph node CFU of noninvasive Escherichia coli Nissle and Salmonella enterica serotype Typhimurium, the latter of which is naturally invasive in mice. Dietary supplementation of malarial-parasite-infected mice with l-arginine or l-citrulline reduced levels of ileal transcripts encoding interleukin-4 (IL-4), a key mediator of intestinal mastocytosis and macromolecular permeability. Supplementation with l-citrulline also enhanced epithelial adherens and tight junctions in the ilea of coinfected mice. These data suggest that increasing l-arginine bioavailability via oral supplementation can ameliorate malaria-induced intestinal pathology, providing a basis for testing nutritional interventions to reduce malaria-associated mortality in humans. PMID:23690397

  2. The influence of a novel pentadecapeptide, BPC 157, on N(G)-nitro-L-arginine methylester and L-arginine effects on stomach mucosa integrity and blood pressure.

    PubMed

    Sikirić, P; Seiwerth, S; Grabarević, Z; Rucman, R; Petek, M; Jagić, V; Turković, B; Rotkvić, I; Mise, S; Zoricić, I; Konjevoda, P; Perović, D; Jurina, L; Separović, J; Hanzevacki, M; Artuković, B; Bratulić, M; Tisljar, M; Gjurasin, M; Miklić, P; Stancić-Rokotov, D; Slobodnjak, Z; Jelovac, N; Marović, A

    1997-07-30

    The known effects of a novel stomach pentadecapeptide BPC157 (10 microg or 10 ng/kg), namely its salutary activity against ethanol (96%, i.g.)-induced gastric lesions (simultaneously applied i.p.) and in blood pressure maintenance (given i.v.), were investigated in rats challenged with a combination of N(G)-nitro-L-arginine methylester (L-NAME) (5 mg/kg i.v.), a competitive inhibitor of endothelium nitric oxide (NO)-generation and NO precursor, L-arginine (200 mg/kg i.v.) (D-arginine was ineffective). In the gastric lesions assay, NO agents were given 5 min before ethanol injury and BPC 157 medication. Given alone, BPC157 had an antiulcer effect, as did L-arginine, but L-NAME had no effect. L-NAME completely abolished the effect of L-arginine, whereas it only attenuated the effect of BPC 157. After application of the combination of L-NAME + L-arginine, the BPC157 effect was additionally impaired. In blood pressure studies, compared with L-arginine, pentadecapeptide BPC 157 (without effect on basal normal values) had both a mimicking effect (impaired L-NAME-blood pressure increase, when applied prophylactically and decreased already raised L-NAME values, given at the time of the maximal L-NAME-blood pressure increase (i.e., 10 min after L-NAME)) and preventive activity (L-arginine-induced moderate blood pressure decrease was prevented by BPC 157 pretreatment). When BPC 157 was given 10 min after L-NAME + L-arginine combination, which still led to a blood pressure increase, its previously clear effect (noted in L-NAME treated rats) disappeared. In vitro, in gastric mucosa from rat stomach tissue homogenates, BPC 157, given in the same dose (100 microM) as L-arginine, induced a comparable generation of NO. But, BPC 157 effect could not be inhibited by L-NAME, even when L-NAME was given in a tenfold (100 versus 1000 microM) higher dose than that needed for inhibition of the L-arginine effect. NO synthesis was blunted when the pentadecapeptide BPC 157 and L-arginine

  3. Characterization of casein and poly-l-arginine multilayer films

    NASA Astrophysics Data System (ADS)

    Szyk-Warszyńska, Lilianna; Kilan, Katarzyna; Socha, Robert P.

    2014-06-01

    Thin films containing casein appear to be a promising material for coatings used in the medical area to promote biomineralization. alfa- and beta-casein and poly-L-arginine multilayer films were formed by the layer-by layer technique and their thickness and mass were analyzed by ellipsometry and quartz crystal microbalance with dissipation monitoring (QCM-D). We investigated the effect of the type of casein used for the film formation and of the polyethyleneimine anchoring layer on the thickness and mass of adsorbed films. The analysis of the mass of films during their post-treatment with the solutions of various ionic strength and pH provided the information concerning films stability, while the XPS elemental analysis confirmed binding of calcium ions by the casein embedded in the multilayers.

  4. Characterization of casein and poly-L-arginine multilayer films.

    PubMed

    Szyk-Warszyńska, Lilianna; Kilan, Katarzyna; Socha, Robert P

    2014-06-01

    Thin films containing casein appear to be a promising material for coatings used in the medical area to promote biomineralization. α- and β-casein and poly-L-arginine multilayer films were formed by the layer-by layer technique and their thickness and mass were analyzed by ellipsometry and quartz crystal microbalance with dissipation monitoring (QCM-D). (PLArg/casein) films deposited in 0.15M NaCl exhibit fast (exponential-like) growth of the film thickness with the number of layers. The resulting films were c.a. 10 times thicker than obtained for poly-L-arginine and natural polyanions. We investigated the effect of the type of casein used for the film formation, finding that films with α-casein were slightly thicker than ones with β-casein. The effect of polyethylene imine anchoring layer on the thickness and mass of adsorbed films was similar as for linear polyelectrolyte pairs. Thickness of "wet" films was c.a. two times larger than measured after drying that suggests their large hydration. The analysis of the mass of films during their post-treatment with the solutions of various ionic strength and pH provided the information concerning films stability. Films remain stable in the neutral and weakly basic conditions that includes HEPES buffer, which is widely used in cell culture and biomedical experiments. At the conditions of high ionic strength films swell but their swelling is reversible. Films containing caseins as polyanion appear to be more elastic and the same time more viscous than one formed with polyelectrolyte pairs. XPS elemental analysis confirmed binding of calcium ions by the casein embedded in the multilayers. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. l-arginine modulates inflammation and muscle regulatory genes after a single session of resistance exercise in rats.

    PubMed

    Morais, S R L; Brito, V G B; Mello, W G; Oliveira, S H P

    2018-02-01

    We investigated the skeletal muscle adaptation to l-arginine supplementation prior to a single session of resistance exercise (RE) during the early phase of muscle repair. Wistar rats were randomly assigned into non-exercised (Control), RE plus vehicle (RE); RE plus l-arginine (RE+L-arg) and RE plus aminoguanidine (RE+AG) groups. Animals received four doses of either vehicle (0.9% NaCl), l-arg (1 g/b.w.), or AG (iNOS inhibitor) (50 mg/b.w.). The animals performed a single RE session until the concentric failure (ladder climbing; 80% overload) and the skeletal muscles were harvested at 0, 8, 24, and 48 hours post-RE. The RE resulted in increased neutrophil infiltrate (24 hours post-RE) (3621 vs 11852; P<.0001) associated with enhanced TNF-α (819.49 vs 357.02; P<.005) and IL-6 (3.84 vs 1.08; P<.0001). Prior, l-arginine supplementation attenuates neutrophil infiltration (5622; P<.0001), and also TNF-α (506.01; P<.05) and IL-6 (2.51, P<.05) levels. AG pretreatment mediated an inhibition of iNOS levels similar to levels found in RE group. RE animals displayed increased of atrogin-1 (1.9 fold) and MuRF-1 (3.2 fold) mRNA levels, reversed by l-arg supplementation [atrogin-1 (0.6 fold; P<.001); MuRF-1 (0.8-fold; P<.001)] at 24 hours post-RE. MyoD up-regulated levels were restricted to l-arg treated animals at 24 hours (2.8 vs 1.5 fold; P<.005) and 48 hours post-RE (2.4 vs 1.1 fold; P<.001). AG pretreatment reversed these processes at 24 hours [atrogin-1 (2.1 fold; P<.0001); MuRF-1 (2.5 fold; P<.0001); MyoD (1.4 fold)]. l-arginine supplementation seems to attenuate the resolution of RE-induced muscle inflammation and up-regulates MyoD expression during the early phase of muscle repair. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Oral administration of L-arginine in patients with angina or following myocardial infarction may be protective by increasing plasma superoxide dismutase and total thiols with reduction in serum cholesterol and xanthine oxidase

    PubMed Central

    Tripathi, Pratima; Chandra, M

    2009-01-01

    Administration of L-arginine has been shown to control ischemic injury by producing nitric oxide which dilates the vessels and thus maintains proper blood flow to the myocardium. In the present study attempt has been made to determine whether oral administration of L-arginine has any effect on oxidant/antioxidant homeostasis in ischemic myocardial patients [represented by the patients of acute angina (AA) and acute myocardial infarction (MI)]. L-arginine has antioxidant and antiapoptotic properties, decreases endothelin-1 expression and improves endothelial function, thereby controlling oxidative injury caused during myocardial ischemic syndrome. Effect of L-arginine administration on the status of free radical scavenging enzymes, pro-oxidant enzyme and antioxidants viz. total thiols, carbonyl content and plasma ascorbic acid levels in the patients has been evaluated. We have observed that L-arginine administration (three grams per day for 15 days) resulted in increased activity of free radical scavenging enzyme superoxide dismutase (SOD) and increase in the levels of total thiols (T-SH) and ascorbic acid with concomitant decrease in lipid per-oxidation, carbonyl content, serum cholesterol and the activity of proxidant enzyme, xanthine oxidase (XO). These findings suggest that the supplementation of L-arginine along with regular therapy may be beneficial to the patients of ischemic myocardial syndromes. PMID:20716909

  7. l-Arginine modulates neonatal lymphocyte proliferation through an interleukin-2 independent pathway

    PubMed Central

    Yu, Hong-Ren; Kuo, Ho-Chang; Huang, Li-Tung; Chen, Chih-Cheng; Tain, You-Lin; Sheen, Jiunn-Ming; Tiao, Mao-Meng; Huang, Hsin-Chun; Yang, Kuender D; Ou, Chia-Yo; Hsu, Te-Yao

    2014-01-01

    In cases of arginine depletion, lymphocyte proliferation, cytokine production and CD3ζ chain expression are all diminished. In addition to myeloid suppressor cells, polymorphonuclear cells (PMN) also exert T-cell immune suppressive effects through arginase-induced l-arginine depletion, especially during pregnancy. In this study, we investigated how arginase/l-arginine modulates neonatal lymphocyte proliferation. Results showed that the neonatal plasma l-arginine level was lower than in adults (48·1 ± 11·3 versus 86·5 ± 14·6 μm; P = 0·003). Neonatal PMN had a greater abundance of arginase I protein than adult PMN. Both transcriptional regulation and post-transcriptional regulation were responsible for the higher arginase I expression of neonatal PMN. Exogenous l-arginine enhanced neonate lymphocyte proliferation but not that of adult cells. The RNA-binding protein HuR was important but was not the only modulation factor in l-arginine-regulated neonatal T-cell proliferation. l-Arginine-mediated neonatal lymphocyte proliferation could not be blocked by interleukin-2 receptor blocking antibodies. These results suggest that the altered arginase/l-arginine cascade may be one of the mechanisms that contribute to altered neonatal immune responses. Exogenous l-arginine could enhance neonate lymphocyte proliferation through an interleukin-2-independent pathway. PMID:24697328

  8. L-arginine plus drospirenone-ethinyl estradiol in the treatment of patients with PCOS: a prospective, placebo controlled, randomised, pilot study.

    PubMed

    Battaglia, Cesare; Mancini, Fulvia; Battaglia, Bruno; Facchinetti, Fabio; Artini, Paolo G; Venturoli, Stefano

    2010-12-01

    To verify the effects of a pill containing drospirenone on the surrogate markers of arterial function and to evaluate the possible improvements induced by the addition of L-arginine. A prospective, placebo controlled, randomised, pilot study. University of Bologna. Twenty-eight young women with PCOS. Random submission to: drospirenone + ethinylestradiol+ a placebo (Group I; n = 15) or drospirenone + ethinylestradiol + oral L-arginine (4 g × 2/daily) (Group II, n = 13). Medical examination; blood measurement of nitrites/nitrates, biochemical and hormonal parameters; ultrasonographic analysis and colour Doppler evaluation of uterine, stromal ovarian and ophthalmic arteries; analysis of brachial artery flow-mediated vasodilatation; and 24-h ambulatory blood pressure monitoring. The above parameters were evaluated before and after 6 months. The low dose oral contraceptive containing drospirenone favoured a pre-hypertensive state. The L-arginine supplementation increased the circulating levels of nitrites/nitrates and improved the endothelium-dependent vasodilatation counteracting the negative effect of the contraceptive pill. Although, the present pilot study was conducted in a limited number of patients, it seems that the L-arginine co-treatment may improve the long-term side effects of the pill reducing the risk of cardiovascular diseases.

  9. Pretreatment and Treatment With L-Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis.

    PubMed

    Andrade, Maria Emília Rabelo; Santos, Rosana das Graças Carvalho Dos; Soares, Anne Danieli Nascimento; Costa, Kátia Anunciação; Fernandes, Simone Odília Antunes; de Souza, Cristina Maria; Cassali, Geovanni Dantas; de Souza, Adna Luciana; Faria, Ana Maria Caetano; Cardoso, Valbert Nascimento

    2016-11-01

    Imbalances in a variety of factors, including genetics, intestinal flora, and mucosal immunity, can contribute to the development of ulcerative colitis and its side effects. This study evaluated the effects of pretreatment or treatment with arginine by oral administration on intestinal permeability, bacterial translocation (BT), and mucosal intestinal damage due to colitis. C57BL/6 mice were distributed into 4 groups: standard diet and water (C: control group), standard diet and dextran sodium sulfate (DSS) solution (Col: colitis group), 2% L-arginine supplementation for 7 days prior to DSS administration and during disease induction (PT: pretreated group), and 2% L-arginine supplementation during disease induction (T: treated group). Colitis was induced by administration of 1.5% DSS for 7 days. After 14 days, intestinal permeability and BT were evaluated; colons were collected for histologic analysis and determination of cytokines; feces were collected for measurement of immunoglobulin A (IgA). The Col group showed increased intestinal permeability (C vs Col: P < .05) and BT (C vs Col: P < .05). In the arginine-supplemented groups (PT and T), this amino acid tended to decrease intestinal permeability. Arginine decreased BT to liver during PT (P < .05) and to blood, liver, spleen, and lung during T (P < .05). Histologic analysis showed that arginine preserved the intestinal mucosa and tended to decreased inflammation. Arginine attenuates weight loss and BT in mice with colitis. © 2015 American Society for Parenteral and Enteral Nutrition.

  10. Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death.

    PubMed

    Movafegh, Bahareh; Jalal, Razieh; Mohammadi, Zobeideh; Aldaghi, Seyyede Araste

    2018-04-11

    Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and ethidium bromide-acridine orange stainings, flow cytometry using annexin V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3 activity were used to examine the influence of poly-L-arginine on doxorubicin-induced cell death. Poly-L-arginine had no cytotoxicity at low concentrations and short exposure times. Poly-L-arginine increased the cytotoxic effect of doxorubicin in DU145 cells in a time-dependent manner. But no significant reduction was found in HFF cell viability. Poly-L-arginine seems to facilitate doxorubicin uptake and increase its intracellular concentration. 24 h combined treatment of cells with doxorubicin (0.5 μM) and poly-L-arginine (1 μg ml-1) caused a small increase in doxorubicin-induced apoptosis and significant elevated necrosis in DU145 cells as compared to each agent alone. Conlusion: Our results indicate that poly-L-arginine at lowest and highest concentrations act as proliferation-inducing and antiproliferative agents, respectively. Between these concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and its cytotoxicity through induction of necrosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. The effects of L-arginine, alone and combined with vitamin C, on mineral status in relation to its antidiabetic, anti-inflammatory, and antioxidant properties in male rats on a high-fat diet.

    PubMed

    Suliburska, Joanna; Bogdanski, Paweł; Krejpcio, Zbigniew; Pupek-Musialik, Danuta; Jablecka, Anna

    2014-01-01

    The aim of this study was to evaluate the influence of the intake of L-arginine alone and of L-arginine with vitamin C on mineral concentration in rats fed with a high-fat diet, and to assess the lipid glucose, insulin, and total antioxidant status (TAS) and tumor necrosis factor (TNF) alpha serum levels that result. Wistar rats were assigned to groups fed with either a standard control diet (C), a diet high in fat (FD), a diet high in fat with L-arginine, or a diet high in fat with L-arginine and vitamin C. After 6 weeks, the length and weight of the rats were measured, and the animals were euthanized. The liver, spleen, kidneys, pancreas, heart, and gonads were collected, as were blood samples. The total serum cholesterol, triglyceride, fasting glucose, insulin, TAS, and TNF alpha levels were measured. The tissue calcium, magnesium, iron, zinc, and copper concentrations were determined. It was found that L-arginine supplementation diminished the effect of the modified diet on the concentration of iron in the liver and spleen and of copper in heart. At the same time, it was observed that L-arginine supplementation reduced the effect of the high-fat diet on insulin, TNF alpha, and TAS. The combination of L-arginine and vitamin C produced a similar effect on the mineral levels in the tissues as did L-arginine used alone. Moreover, positive correlations between serum insulin and iron in the liver, between TNF alpha and iron in the liver, and between TNF alpha and copper in the heart were observed. The level of TAS in serum was inversely correlated with the copper level in the heart and the iron level in the liver. We concluded that the beneficial influence of L-arginine on insulin, TAS, and TNF alpha serum level is associated with changes in the iron and copper status in rats fed with a high-fat diet. No synergistic effect of L-arginine and vitamin C in the biochemical parameters or in the mineral status in rats fed with the modified diet was observed.

  12. L-arginine-induced vasodilation in healthy humans: pharmacokinetic–pharmacodynamic relationship

    PubMed Central

    Bode-Böger, Stefanie M; Böger, Rainer H; Galland, Andrea; Tsikas, Dimitrios; Frölich, Jürgen C

    1998-01-01

    Aims Administration of l-arginine by intravenous infusion or via oral absorption has been shown to induce peripheral vasodilation in humans, and to improve endothelium-dependent vasodilation. We investigated the pharmacokinetics and pharmacokinetic-pharmacodynamic relationship of l-arginine after a single intravenous infusion of 30 g or 6 g, or after a single oral application of 6 g, as compared with the respective placebo, in eight healthy male human subjects. Methods l-arginine levels were determined by h.p.l.c. The vasodilator effects of l-arginine were assessed non-invasively by blood pressure monitoring and impedance cardiography. Urinary nitrate and cyclic GMP excretion rates were measured as non-invasive indicators of endogenous NO production. Results Plasma l-arginine levels increased to (mean±s.e.mean) 6223±407 (range, 5100–7680) and 822±59 (527–955) μmol l−1 after intravenous infusion of 30 g and 6 g l-arginine, respectively, and to 310±152 (118–1219) μmol l−1 after oral ingestion of 6 g l-arginine. Oral bioavailability of l-arginine was 68±9 (51–87)%. Clearance was 544±24 (440–620), 894±164 (470–1190), and 1018±230 (710–2130) ml min−1, and elimination half-life was calculated as 41.6±2.3 (34–55), 59.6±9.1 (24–98), and 79.5±9.3 (50–121) min, respectively, for 30 g i.v., 6 g i.v., and 6 g p.o. of l-arginine. Blood pressure and total peripheral resistance were significantly decreased after intravenous infusion of 30 g l-arginine by 4.4±1.4% and 10.4±3.6%, respectively, but were not significantly changed after oral or intravenous administration of 6 g l-arginine. l-arginine (30 g) also significantly increased urinary nitrate and cyclic GMP excretion rates by 97±28 and 66±20%, respectively. After infusion of 6 g l-arginine, urinary nitrate excretion also significantly increased, (nitrate by 47±12% [P < 0.05], cyclic GMP by 67±47% [P = ns]), although to a lesser and more variable extent than after 30 g of l-arginine

  13. N-carbamylglutamate and L-arginine improved maternal and placental development in underfed ewes.

    PubMed

    Zhang, Hao; Sun, Lingwei; Wang, Ziyu; Deng, Mingtian; Nie, Haitao; Zhang, Guomin; Ma, Tiewei; Wang, Feng

    2016-06-01

    The objectives of this study were to determine how dietary supplementation of N-carbamylglutamate (NCG) and rumen-protected L-arginine (RP-Arg) in nutrient-restricted pregnant Hu sheep would affect (1) maternal endocrine status; (2) maternal, fetal, and placental antioxidation capability; and (3) placental development. From day 35 to day 110 of gestation, 32 Hu ewes carrying twin fetuses were allocated randomly into four groups: 100% of NRC-recommended nutrient requirements, 50% of NRC recommendations, 50% of NRC recommendations supplemented with 20g/day RP-Arg, and 50% of NRC recommendations supplemented with 5g/day NCG product. The results showed that in maternal and fetal plasma and placentomes, the activities of total antioxidant capacity and superoxide dismutase were increased (P<0.05); however, the activity of glutathione peroxidase and the concentration of maleic dialdehyde were decreased (P<0.05) in both NCG- and RP-Arg-treated underfed ewes. The mRNA expression of vascular endothelial growth factor and Fms-like tyrosine kinase 1 was increased (P<0.05) in 50% NRC ewes than in 100% NRC ewes, and had no effect (P>0.05) in both NCG- and RP-Arg-treated underfed ewes. A supplement of RP-Arg and NCG reduced (P<0.05) the concentrations of progesterone, cortisol, and estradiol-17β; had no effect on T4/T3; and improved (P<0.05) the concentrations of leptin, insulin-like growth factor 1, tri-iodothyronine (T3), and thyroxine (T4) in serum from underfed ewes. These results indicate that dietary supplementation of NCG and RP-Arg in underfed ewes could influence maternal endocrine status, improve the maternal-fetal-placental antioxidation capability, and promote fetal and placental development during early-to-late gestation. © 2016 Society for Reproduction and Fertility.

  14. Alterations in plasma L-arginine and methylarginines in heart failure and after heart transplantation.

    PubMed

    Lundgren, Jakob; Sandqvist, Anna; Hedeland, Mikael; Bondesson, Ulf; Wikström, Gerhard; Rådegran, Göran

    2018-04-12

    Endothelial function, including the nitric oxide (NO)-pathway, has previously been extensively investigated in heart failure (HF). In contrast, studies are lacking on the NO pathway after heart transplantation (HT). We therefore investigated substances in the NO pathway prior to and after HT in relation to hemodynamic parameters. 12 patients (median age 50.0 yrs, 2 females), heart transplanted between June 2012 and February 2014, evaluated at our hemodynamic lab, at rest, prior to HT, as well as four weeks and six months after HT were included. All patients had normal left ventricular function post-operatively and none had post-operative pulmonary hypertension or acute cellular rejection requiring therapy at the evaluations. Plasma concentrations of ADMA, SDMA, L-Arginine, L-Ornithine and L-Citrulline were analyzed at each evaluation. In comparison to controls, the plasma L-Arginine concentration was low and ADMA high in HF patients, resulting in low L-Arginine/ADMA-ratio pre-HT. Already four weeks after HT L-Arginine was normalized whereas ADMA remained high. Consequently the L-Arginine/ADMA-ratio improved, but did not normalize. The biomarkers remained unchanged at the six-month evaluation and the L-Arginine/ADMA-ratio correlated inversely to pulmonary vascular resistance (PVR) six months post-HT. Plasma L-Arginine concentrations normalize after HT. However, as ADMA is unchanged, the L-Arginine/ADMA-ratio remained low and correlated inversely to PVR. Together these findings suggest that (i) the L-Arginine/ADMA-ratio may be an indicator of pulmonary vascular tone after HT, and that (ii) NO-dependent endothelial function is partly restored after HT. Considering the good postoperative outcome, the biomarker levels may be considered "normal" after HT.

  15. L-Arginine in the treatment of valproate overdose - five clinical cases.

    PubMed

    Schrettl, Verena; Felgenhauer, Norbert; Rabe, Christian; Fernando, Malkanthi; Eyer, Florian

    2017-04-01

    Valproic acid and its metabolites - particularly valproyl-CoA - are inhibitors of the enzyme N-acetylglutamate synthetase. The amino acid l-arginine can stimulate N-acetylglutamate synthetase activity and could be potentially used therapeutically to correct hyperammonemia caused by valproate therapy or overdose. Severely valproic-acid-poisoned patients are usually treated with l-carnitine or hemodialysis in order to decrease hyperammonemia. We herein report of five cases, in which l-arginine was administered. Observational study on five cases. Patients with hyperammonemia (i.e., ammonia 80 > μg/dL) and symptoms consistent with valproate overdose (i.e., drowsiness, coma) were selected for treatment with l-arginine. Data was collected retrospectively. l-Arginine decreased ammonia levels in a close temporal relation (case I ammonia in EDTA-plasma [μg/dL] decreased from 381 to 39; case II from 281 to 50; case III from 669 to 74; case IV from 447 to 56; case V from 202 to 60). In cases I and II, hemodialysis was performed and l-carnitine was given before the administration of l-arginine. In case III, hemodialysis was performed after the administration of l-arginine was already started. In cases IV and V, treatment with l-arginine was the sole measure to decrease ammonia levels in plasma. The results suggest that l-arginine may be beneficial in selected cases of valproate overdose complicated by hyperammonemia. l-Arginine could extend our conventional treatment options for valproic acid overdose.

  16. Renal Response to L-Arginine in Diabetic Rats. A Possible Link between Nitric Oxide System and Aquaporin-2

    PubMed Central

    Ortiz, María C.; Albertoni Borghese, María F.; Balonga, Sabrina E.; Lavagna, Agustina; Filipuzzi, Ana L.; Elesgaray, Rosana; Costa, María A.; Majowicz, Mónica P.

    2014-01-01

    The aim of this study was to evaluate whether L-Arginine (L-Arg) supplementation modifies nitric oxide (NO) system and consequently aquaporin-2 (AQP2) expression in the renal outer medulla of streptozotocin-diabetic rats at an early time point after induction of diabetes. Male Wistar rats were divided in four groups: Control, Diabetic, Diabetic treated with L-Arginine and Control treated with L-Arginine. Nitric oxide synthase (NOS) activity was estimated by [14C] L-citrulline production in homogenates of the renal outer medulla and by NADPH-diaphorase staining in renal outer medullary tubules. Western blot was used to detect the expression of AQP2 and NOS types I and III; real time PCR was used to quantify AQP2 mRNA. The expression of both NOS isoforms, NOS I and NOS III, was decreased in the renal outer medulla of diabetic rats and L-Arg failed to prevent these decreases. However, L-Arg improved NO production, NADPH-diaphorase activity in collecting ducts and other tubular structures, and NOS activity in renal homogenates from diabetic rats. AQP2 protein and mRNA were decreased in the renal outer medulla of diabetic rats and L-Arg administration prevented these decreases. These results suggest that the decreased NOS activity in collecting ducts of the renal outer medulla may cause, at least in part, the decreased expression of AQP2 in this model of diabetes and constitute additional evidence supporting a role for NO in contributing to renal water reabsorption through the modulation of AQP2 expression in this pathological condition. However, we cannot discard that another pathway different from NOS also exists that links L-Arg to AQP2 expression. PMID:25111608

  17. Renal response to L-arginine in diabetic rats. A possible link between nitric oxide system and aquaporin-2.

    PubMed

    Ortiz, María C; Albertoni Borghese, María F; Balonga, Sabrina E; Lavagna, Agustina; Filipuzzi, Ana L; Elesgaray, Rosana; Costa, María A; Majowicz, Mónica P

    2014-01-01

    The aim of this study was to evaluate whether L-Arginine (L-Arg) supplementation modifies nitric oxide (NO) system and consequently aquaporin-2 (AQP2) expression in the renal outer medulla of streptozotocin-diabetic rats at an early time point after induction of diabetes. Male Wistar rats were divided in four groups: Control, Diabetic, Diabetic treated with L-Arginine and Control treated with L-Arginine. Nitric oxide synthase (NOS) activity was estimated by [14C] L-citrulline production in homogenates of the renal outer medulla and by NADPH-diaphorase staining in renal outer medullary tubules. Western blot was used to detect the expression of AQP2 and NOS types I and III; real time PCR was used to quantify AQP2 mRNA. The expression of both NOS isoforms, NOS I and NOS III, was decreased in the renal outer medulla of diabetic rats and L-Arg failed to prevent these decreases. However, L-Arg improved NO production, NADPH-diaphorase activity in collecting ducts and other tubular structures, and NOS activity in renal homogenates from diabetic rats. AQP2 protein and mRNA were decreased in the renal outer medulla of diabetic rats and L-Arg administration prevented these decreases. These results suggest that the decreased NOS activity in collecting ducts of the renal outer medulla may cause, at least in part, the decreased expression of AQP2 in this model of diabetes and constitute additional evidence supporting a role for NO in contributing to renal water reabsorption through the modulation of AQP2 expression in this pathological condition. However, we cannot discard that another pathway different from NOS also exists that links L-Arg to AQP2 expression.

  18. Synthesis, characterization and properties of L-arginine-passivated silver nanocolloids

    SciTech Connect

    Sunatkari, A. L., E-mail: ashok.sunatkari@rediffmail.com; Talwatkar, S. S.; Tamgadge, Y. S.

    2016-05-06

    We investigate the effect of L-arginine-surface passivation on localised surface plasmon resonance (LSPR), size and stability of colloidal Silver Nanoparticles (AgNPs) synthesized by chemical reduction method. The surface Plasmon resonance absorption peak of AgNPs shows blue shift with the increase in L-arginine concentration. Transmission electron microscopy (TEM) analysis confirmed that the average size of AgNPs reduces from 10 nm to 6 nm as the concentration of L-Arginine increased from 1 to 5 mM. The X-ray diffraction study (XRD) confirmed the formation face-centred cubic (fcc) structured AgNPs. FT-IR studies revealed strong bonding between L-arginine functional groups and AgNPs.

  19. Does L-arginine induce intestinal adaptation by epithelial growth factor?

    PubMed

    Camli, Alparslan; Barlas, Meral; Yagmurlu, Aydin

    2005-01-01

    To evaluate whether L-Arginine has an effect on endogenous epidermal growth factor secretion and intestinal adaptation in massive small bowel resection an experimental study was performed. Fourteen albino Wistar rats weighing 250-300 g were used for the study. After performing 50% small bowel resection and anastomosis the rats were randomly divided into two groups. The first group received 500 mg/kg/day of L-Arginine intraperitoneally for 14 days just after the surgical procedure. The control group received isotonic saline instead. Body weight measurement was preformed daily. At the end of the second postoperative week all rats underwent relaparotomy. Small bowel was resected for histopathological examination. Levels of epidermal growth factor were measured by enzyme-linked immunosorbent assay in serum, saliva, and urine at the end of second postoperative week in both groups. The weight gain was higher in the L-Arginine treated group (P < 0.05). Serum, saliva and urinary epidermal growth factor levels were significantly higher at the end of the second week compared to the control group (P < 0.05). The villus height was higher on histopathological examination in L-Arginine treated group compared to the control group (P < 0.05). L-Arginine resulted in a better intestinal adaptation after massive bowel resection. The high levels of epidermal growth factor in body fluids of L-Arginine treated rats could be the explanation for this effect.

  20. Improvement of retinal functions after ischemia with L-arginine and its derivatives.

    PubMed

    Liu, S X; Chiou, G C; Varma, R S

    1995-01-01

    Retinal ischemia was created by occlusion of rat central retinal artery for 30 minutes. The loss of retinal function was indicated by the loss of b-wave of electroretinogram. The recovery of retinal function after reperfusion of central retinal artery was observed with the gradual recovery of b-wave amplitude to approximately 20% of original b-wave amplitude. When L-arginine (RVC-579) was administered at the time of retina ischemia, the b-wave amplitudes recovered up to 64% of original height and were significantly higher than corresponding controls at 120, 180, and 240 min after ischemia. When the derivative of L-arginine, N alpha-benzoyl-L-arginine ethyl ester (RVC-578), was administered, the b-wave recovery was significantly higher than corresponding controls at 90, 120, 180, and 240 min after ischemia; the recovery reached 51% of the original b-wave value. These results indicate that the L-arginine and its lipophilic derivatives could be used for the treatment of ischemic retinopathy. Since L-arginine is a natural amino acid, it is not expected to produce major side effects, if any, and could pave the way for the development of a safer drug to be used in the clinics. Compounds which increase the formation of NO in vivo, dilate blood vessels. Both L-arginine and RVC-578 can be placed in this category. They may improve effects of retinal ischemia by increasing NO production.

  1. L-Arginine regulates protein turnover in porcine mammary epithelial cells to enhance milk protein synthesis.

    PubMed

    Ma, Qingquan; Hu, Shengdi; Bannai, Makoto; Wu, Guoyao

    2018-05-01

    Milk is an important food for mammalian neonates, but its insufficient production is a nutritional problem for humans and other animals. Recent studies indicate that dietary supplementation with L-arginine (Arg) increases milk production in mammals, including sows, rabbits, and cows. However, the underlying molecular mechanisms remain largely unknown. The present study was conducted with porcine mammary epithelial cells (PMECs) to test the hypothesis that Arg enhances milk protein synthesis via activation of the mechanistic target of rapamycin (mTOR) cell signaling. PMECs were cultured for 4 days in Arg-free basal medium supplemented with 10, 50, 200, or 500 μmol/L Arg. Rates of protein synthesis and degradation in cells were determined with the use of L-[ring-2,4- 3 H]phenylalanine. Cell medium was analyzed for β-casein and α-lactalbumin, whereas cells were used for quantifying total and phosphorylated levels of mTOR, ribosomal protein S6 kinase (p70S6K), 4E-binding protein 1 (4EBP1), ubiquitin, and proteasome. Addition of 50-500 μmol/L Arg to culture medium increased (P < 0.05) the proliferation of PMECs and the synthesis of proteins (including β-casein and α-lactalbumin), while reducing the rates of proteolysis, in a dose-dependent manner. The phosphorylated levels of mTOR, p70S6K and 4EBP1 were elevated (P < 0.05), but the abundances of ubiquitin and proteasome were lower (P < 0.05), in PMECs supplemented with 200-500 μmol/L Arg, compared with 10-50 μmol/L Arg. These results provide a biochemical basis for the use of Arg to enhance milk production by sows and have important implications for improving lactation in other mammals (including humans and cows).

  2. Mannitol/l-Arginine-Based Formulation Systems for Freeze Drying of Protein Pharmaceuticals: Effect of the l-Arginine Counter Ion and Formulation Composition on the Formulation Properties and the Physical State of Mannitol.

    PubMed

    Stärtzel, Peter; Gieseler, Henning; Gieseler, Margit; Abdul-Fattah, Ahmad M; Adler, Michael; Mahler, Hanns-Christian; Goldbach, Pierre

    2016-10-01

    Previous studies have shown that protein storage stability in freeze-dried l-arginine-based systems improved in the presence of chloride ions. However, chloride ions reduced the glass transition temperature of the freeze concentrate (Tg') and made freeze drying more challenging. In this study, l-arginine was freeze dried with mannitol to obtain partially crystalline solids that can be freeze dried in a fast process and result in elegant cakes. We characterized the effect of different l-arginine counter ions on physicochemical properties of mannitol compared with mannitol/sucrose systems. Thermal properties of formulations with different compositions were correlated to thermal history during freeze drying and to physicochemical properties (cake appearance, residual moisture, reconstitution time, crystallinity). Partially crystalline solids were obtained even at the highest l-arginine level (mannitol:l-arginine of 2:1) used in this study. All l-arginine-containing formulations yielded elegant cakes. Only cakes containing l-arginine chloride and succinate showed a surface "crust" formed by phase separation. X-ray powder diffraction showed that inhibition of mannitol crystallization was stronger for l-arginine compared with sucrose and varied with the type of l-arginine counter ion. The counter ion affected mannitol polymorphism and higher levels of mannitol hemi-hydrate were obtained at high levels of l-arginine chloride. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. L-arginine and Arginase Products Potentiate Dexmedetomidine-induced Contractions in the Rat Aorta.

    PubMed

    Wong, Emily S W; Man, Ricky Y K; Ng, Kwok F J; Leung, Susan W S; Vanhoutte, Paul M

    2018-03-01

    The α2-adrenergic sedative/anesthetic agent dexmedetomidine exerts biphasic effects on isolated arteries, causing endothelium-dependent relaxations at concentrations at or below 30 nM, followed by contractions at higher concentrations. L-arginine is a common substrate of endothelial nitric oxide synthase and arginases. This study was designed to investigate the role of L-arginine in modulating the overall vascular response to dexmedetomidine. Isometric tension was measured in isolated aortic rings of Sprague Dawley rats. Cumulative concentrations of dexmedetomidine (10 nM to 10 μM) were added to quiescent rings (with and without endothelium) after previous incubation with vehicle, N-nitro-L-arginine methyl ester hydrochloride (L-NAME; nitric oxide synthase inhibitor), prazosin (α1-adrenergic antagonist), rauwolscine (α2-adrenergic antagonist), L-arginine, (S)-(2-boronethyl)-L-cysteine hydrochloride (arginase inhibitor), N-hydroxy-L-arginine (arginase inhibitor), urea and/or ornithine. In some preparations, immunofluorescent staining, immunoblotting, or measurement of urea content were performed. Dexmedetomidine did not contract control rings with endothelium but evoked concentration-dependent increases in tension in such rings treated with L-NAME (Emax 50 ± 4%) or after endothelium-removal (Emax 74 ± 5%; N = 7 to 12). Exogenous L-arginine augmented the dexmedetomidine-induced contractions in the presence of L-NAME (Emax 75 ± 3%). This potentiation was abolished by (S)-(2-boronethyl)-L-cysteine hydrochloride (Emax 16 ± 4%) and N-hydroxy-L-arginine (Emax 18 ± 4%). Either urea or ornithine, the downstream arginase products, had a similar potentiating effect as L-arginine. Immunoassay measurements demonstrated an upregulation of arginase I by L-arginine treatment in the presence of L-NAME (N = 4). These results suggest that when vascular nitric oxide homeostasis is impaired, the potentiation of the vasoconstrictor effect of

  4. New Insights into the Methodology of L-Arginine-Induced Acute Pancreatitis

    PubMed Central

    Kui, Balázs; Balla, Zsolt; Vasas, Béla; Végh, Eszter T.; Pallagi, Petra; Kormányos, Eszter S.; Venglovecz, Viktória; Iványi, Béla; Takács, Tamás; Hegyi, Péter; Rakonczay, Zoltán

    2015-01-01

    Animal models are ideal to study the pathomechanism and therapy of acute pancreatitis (AP). The use of L-arginine-induced AP model is nowadays becoming increasingly popular in mice. However, carefully looking through the literature, marked differences in disease severity could be observed. In fact, while setting up the L-arginine (2×4 g/kg i.p.)-induced AP model in BALB/c mice, we found a relatively low rate (around 15%) of pancreatic necrosis, whereas others have detected much higher rates (up to 55%). We suspected that this may be due to differences between mouse strains. We administered various concentrations (5–30%, pH = 7.4) and doses (2×4, 3×3, or 4×2.5 g/kg) of L-arginine-HCl in BALB/c, FVB/n and C57BL/6 mice. The potential gender-specific effect of L-arginine was investigated in C57BL/6 mice. The fate of mice in response to the i.p. injections of L arginine followed one of three courses. Some mice (1) developed severe AP or (2) remained AP-free by 72 h, whereas others (3) had to be euthanized (to avoid their death, which was caused by the high dose of L-arginine and not AP) within 12 h., In FVB/n and C57BL/6 mice, the pancreatic necrosis rate (about 50%) was significantly higher than that observed in BALB/c mice using 2×4 g/kg 10% L–arginine, but euthanasia was necessary in a large proportion of animals, The i.p. injection of lower L-arginine concentrations (e.g. 5–8%) in case of the 2×4 g/kg dose, or other L-arginine doses (3×3 or 4×2.5 g/kg, 10%) were better for inducing AP. We could not detect any significant differences between the AP severity of male and female mice. Taken together, when setting up the L-arginine-induced AP model, there are several important factors that are worth consideration such as the dose and concentration of the administered L arginine-HCl solution and also the strain of mice. PMID:25688985

  5. Dependence of endotoxin-induced vascular hyporeactivity on extracellular L-arginine.

    PubMed

    Schott, C A; Gray, G A; Stoclet, J C

    1993-01-01

    1. The dependence on extracellular L-arginine of vascular hyporeactivity induced by bacterial lipopolysaccharide (LPS) was studied in vivo in rats infused with LPS and in vitro in endothelium-denuded rat thoracic aortic rings exposed to LPS. 2. Infusion of LPS during 50 min at a dose of 10 mg kg-1 h-1 produced a significant impairment of the pressor effect of noradrenaline, while in tissues collected 60 min after the start of LPS infusion, no significant alteration in either plasma arginine concentration or aortic arginine content was found compared to saline-infused controls (where plasma arginine was 78.5 +/- 7 microM and aortic arginine 394 +/- 124 nmol g-1 tissue). 3. Incubation of isolated, endothelium-denuded aortic rings with LPS (10 micrograms ml-1) in the absence of L-arginine for 4 h at 37 degrees C produced a 6 fold (P < 0.01) rightward shift in the noradrenaline concentration-effect curve compared to polymyxin B (1 micrograms ml-1, a LPS neutralizing agent) and reduced by 15% the maximum observed tension. 4. The presence of L-arginine (100 microM) during the incubation with LPS and throughout the following contraction experiments caused a 15 fold (P < 0.01) increase in the EC50 of noradrenaline and greater depression (45%) of the maximum observed tension compared to polymyxin B-treated controls. Responses in control, non LPS-treated rings were unaffected by the presence of L-arginine. 5. The addition of L-arginine to rings incubated with LPS in the absence of L-arginine and maximally precontracted with noradrenaline (10 microM) induced a dose-dependent relaxation. The EC50 of L-arginine was 8.0+/-0.3mu.6. The reactivity of LPS-treated rings to noradrenaline both in the absence and presence of L-arginine was restored to control levels by N0-nitro-L-arginine methyl ester (L-NAME, 300 mu), an inhibitor of NO production and by methylene blue (3 JAM), an inhibitor of guanylate cyclase.7. Incubation of isolated aortae in the absence of L-arginine did not

  6. Pharmacokinetics, safety, and effects on exercise performance of L-arginine alpha-ketoglutarate in trained adult men.

    PubMed

    Campbell, Bill; Roberts, Mike; Kerksick, Chad; Wilborn, Colin; Marcello, Brandon; Taylor, Lem; Nassar, Erika; Leutholtz, Brian; Bowden, Rodney; Rasmussen, Chris; Greenwood, Mike; Kreider, Richard

    2006-09-01

    We evaluated the pharmacokinetics, safety, and efficacy of l-arginine alpha-ketoglutarate (AAKG) in trained adult men. Subjects participated in two studies that employed a randomized, double-blind, controlled design. In study 1, 10 healthy men (30-50 y old) fasted for 8 h and then ingested 4 g of time-released or non-timed-released AAKG. Blood samples were taken for 8 h after AAKG ingestion to assess the pharmacokinetic profile of L-arginine. After 1 wk the alternative supplement was ingested. In study 2, which was placebo controlled, 35 resistance-trained adult men (30-50 y old) were randomly assigned to ingest 4 g of AAKG (three times a day, i.e., 12 g daily, n = 20) or placebo (n = 15). Participants performed 4 d of periodized resistance training per week for 8 wk. At 0, 4, and 8 wk of supplementation the following tests were performed: clinical blood markers, one repetition maximum bench press, isokinetic quadriceps muscle endurance, anaerobic power, aerobic capacity, total body water, body composition, and psychometric parameters tests. Data were analyzed by repeated measures analysis of variance. In study 1, significant differences were observed in plasma arginine levels in subjects taking non-timed-release and timed-release AAKG. In study 2, significant differences were observed in the AAKG group (P < 0.05) for 1RM bench press, Wingate peak power, blood glucose, and plasma arginine. No significant differences were observed between groups in body composition, total body water, isokinetic quadriceps muscle endurance, or aerobic capacity. AAKG supplementation appeared to be safe and well tolerated, and positively influenced 1RM bench press and Wingate peak power performance. AAKG did not influence body composition or aerobic capacity.

  7. Cloning and expression of phosphoenolpyruvate carboxykinase from a cestode parasite and its solubilization from inclusion bodies using l-arginine.

    PubMed

    Dutta, Asim K; Ramnath; Dkhar, Barilin; Tandon, Veena; Das, Bidyadhar

    2016-09-01

    Phosphoenolpyruvate carboxykinase is an essential regulatory enzyme of glycolysis in the cestode parasite, Raillietina echinobothrida, and is considered a potential target for anthelmintic action because of its differential activity from that of its avian host. However, due to the unavailability of its structure, the mechanism of regulation of PEPCK from R. echinobothrida (rePEPCK) and its interaction with possible modulators remain unclear. Hence, in this study, the rePEPCK gene was cloned into pGEX-4T-3 and overexpressed for its characterization. On being induced by IPTG, the recombinant rePEPCK was expressed as inclusion bodies (IBs); hence, various agents, like different inducer concentrations, temperature, time, host cell types, culture media, pH, and additives, were used to bring the protein to soluble form. Finally, a significant amount (∼46%) of rePEPCK was solubilized from IBs by adding 2M l-arginine. Near-UV circular dichroism spectra analysis indicated that l-arginine (2M) had no effect on the conformation of the protein. In this study, we have reported a yield of ∼73mg of purified rePEPCK per 1L of culture. The purified rePEPCK retained its biological activity, and Km of the enzyme for its substrate was determined and discussed. The availability of recombinant rePEPCK may help in biochemical- and biophysical-studies to explore its molecular mechanisms and regulations. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. l-Arginine Pathway Metabolites Predict Need for Intra-operative Shunt During Carotid Endarterectomy.

    PubMed

    Szabo, P; Lantos, J; Nagy, L; Keki, S; Volgyi, E; Menyhei, G; Illes, Z; Molnar, T

    2016-12-01

    Asymmetric dimethylarginine (ADMA) inhibits nitric oxide (NO) synthesis and is a marker of atherosclerosis. This study examined the correlation between pre-operative l-arginine and ADMA concentration during carotid endarterectomy (CEA), and jugular lactate indicating anaerobic cerebral metabolism, jugular S100B reflecting blood-brain barrier integrity, and with factors of surgical intervention. The concentration of l-arginine, ADMA, and symmetric dimethylarginine was measured in blood taken under regional anaesthesia from the radial artery of 55 patients prior to CEA. Blood gas parameters, concentration of lactate, and S100B were also serially measured in blood taken from both the radial artery and the jugular bulb before and after carotid clamping, and after release of the clamp. To estimate anaerobic metabolism, the jugulo-arterial ratio of CO 2 gap/oxygen extraction was calculated. Positive correlation was found between pre-operative ADMA levels and the ratio of jugulo-arterial CO 2 gap/oxygen extraction during clamp and reperfusion (p = .005 and p = .01, respectively). An inverse correlation was found between the pre-operative l-arginine concentration and jugular lactate at each time point (both p = .002). The critical pre-operative level of l-arginine was determined by receiver operator curve analysis. If l-arginine was below the cutoff value of 35 μmol/L, jugular S100B concentration was higher 24 h post-operatively (p = .03), and jugular lactate levels were increased during reperfusion (p = .02). The median pre-operative concentration of l-arginine was lower in patients requiring an intra-operative shunt than in patients without need of shunt (median: 30.3 μmol/L [interquartile range 24.4-34.4 μmol/L] vs. 57.6 μmol/L [interquartile range 42.3-74.5 μmol/L]; p = .002). High pre-operative ADMA concentration predicts poor cerebral perfusion indicated by elevated jugulo-arterial CO 2 gap/oxygen extraction. Low pre-operative l-arginine

  9. Mechanism of Allosteric Inhibition of N-Acetyl-L-glutamate Synthase by L-Arginine

    SciTech Connect

    Min, Li; Jin, Zhongmin; Caldovic, Ljubica

    2010-01-07

    N-Acetylglutamate synthase (NAGS) catalyzes the first committed step in L-arginine biosynthesis in plants and micro-organisms and is subject to feedback inhibition by L-arginine. This study compares the crystal structures of NAGS from Neisseria gonorrhoeae (ngNAGS) in the inactive T-state with L-arginine bound and in the active R-state complexed with CoA and L-glutamate. Under all of the conditions examined, the enzyme consists of two stacked trimers. Each monomer has two domains: an amino acid kinase (AAK) domain with an AAK-like fold but lacking kinase activity and an N-acetyltransferase (NAT) domain homologous to other GCN5-related transferases. Binding of L-arginine to the AAKmore » domain induces a global conformational change that increases the diameter of the hexamer by {approx}10 {angstrom} and decreases its height by {approx}20{angstrom}. AAK dimers move 5{angstrom} outward along their 2-fold axes, and their tilt relative to the plane of the hexamer decreases by {approx}4{sup o}. The NAT domains rotate {approx}109{sup o} relative to AAK domains enabling new interdomain interactions. Interactions between AAK and NAT domains on different subunits also change. Local motions of several loops at the L-arginine-binding site enable the protein to close around the bound ligand, whereas several loops at the NAT active site become disordered, markedly reducing enzymatic specific activity.« less

  10. Mechanism of allosteric inhibition of N-acetyl-L-glutamate synthase by L-arginine.

    PubMed

    Min, Li; Jin, Zhongmin; Caldovic, Ljubica; Morizono, Hiroki; Allewell, Norma M; Tuchman, Mendel; Shi, Dashuang

    2009-02-20

    N-Acetylglutamate synthase (NAGS) catalyzes the first committed step in l-arginine biosynthesis in plants and micro-organisms and is subject to feedback inhibition by l-arginine. This study compares the crystal structures of NAGS from Neisseria gonorrhoeae (ngNAGS) in the inactive T-state with l-arginine bound and in the active R-state complexed with CoA and l-glutamate. Under all of the conditions examined, the enzyme consists of two stacked trimers. Each monomer has two domains: an amino acid kinase (AAK) domain with an AAK-like fold but lacking kinase activity and an N-acetyltransferase (NAT) domain homologous to other GCN5-related transferases. Binding of l-arginine to the AAK domain induces a global conformational change that increases the diameter of the hexamer by approximately 10 A and decreases its height by approximately 20A(.) AAK dimers move 5A outward along their 2-fold axes, and their tilt relative to the plane of the hexamer decreases by approximately 4 degrees . The NAT domains rotate approximately 109 degrees relative to AAK domains enabling new interdomain interactions. Interactions between AAK and NAT domains on different subunits also change. Local motions of several loops at the l-arginine-binding site enable the protein to close around the bound ligand, whereas several loops at the NAT active site become disordered, markedly reducing enzymatic specific activity.

  11. High asymmetric dimethylarginine, symmetric dimethylarginine and L-arginine levels in migraine patients.

    PubMed

    Reyhani, Aylin; Celik, Yahya; Karadag, Hakan; Gunduz, Ozgur; Asil, Talip; Sut, Necdet

    2017-07-01

    Experimental and clinical data strongly suggests that nitric oxide (NO) plays a pivotal role in migraine. This is also supported by studies of migraine induced by substances that release NO. NO is synthesized from L-arginine by endothelial NO synthase (NOS). Asymmetric dimethylarginine (ADMA) is the major endogenous competitive inhibitor of NOS. Symmetric dimethylarginine (SDMA) is an inactive stereoisomer of ADMA. It may reduce NO production by competing with arginine for cellular uptake. The aim of this study was to measure the levels of ADMA, SDMA and L-arginine in migraine patients during the interictal period. One hundred migraine patients and 100 healthy volunteers were recruited. The patients were in the interictal period and classified into two groups as having migraine with aura and migraine without aura. Their serum ADMA, SDMA and L-arginine levels were measured by high-performance liquid chromotography (HPLC) method. ADMA, SDMA and L-arginine levels were significantly higher in migraine patients compared to the control group. But there was no difference between the patients with and without aura. These results suggest that NOS inhibitors and L-arginine/NO pathway plays an important role in migraine pathopysiology.

  12. Apple snack enriched with L-arginine using vacuum impregnation/ohmic heating technology.

    PubMed

    Moreno, Jorge; Echeverria, Julian; Silva, Andrea; Escudero, Andrea; Petzold, Guillermo; Mella, Karla; Escudero, Carlos

    2017-07-01

    Modern life has created a high demand for functional food, and in this context, emerging technologies such as vacuum impregnation and ohmic heating have been applied to generate functional foods. The aim of this research was to enrich the content of the semi-essential amino acid L-arginine in apple cubes using vacuum impregnation, conventional heating, and ohmic heating. Additionally, combined vacuum impregnation/conventional heating and vacuum impregnation/ohmic heating treatments were evaluated. The above treatments were applied at 30, 40 and 50  ℃ and combined with air-drying at 40 ℃ in order to obtain an apple snack rich in L-arginine. Both the impregnation kinetics of L-arginine and sample color were evaluated. The impregnated samples created using vacuum impregnation/ohmic heating at 50 ℃ presented a high content of L-arginine, an effect attributed primarily to electropermeabilization. Overall, vacuum impregnation/ohmic heating treatment at 50 ℃, followed by drying at 40 ℃, was the best process for obtaining an apple snack rich in L-arginine.

  13. Efficiency of cardioplegic solutions containing L-arginine and L-aspartic acid.

    PubMed

    Pisarenko, O I; Shul'zhenko, V S; Studneva, I M

    2006-04-01

    In experiments on rats we studied the effects of cardioplegic solutions with L-aspartic acid or L-arginine on functional recovery and metabolism of isolated working heart after 40-min normothermal global ischemia and 30-min reperfusion. After reperfusion of the hearts preventively protected with cardioplegic solution containing L-aspartic acid or L-arginine, coronary flow decreased in comparison with the initial values. As a component of cardioplegic solution, L-arginine was less efficient in recovery of contractility and cardiac output of the hearts in comparison with L-aspartic acid. In hearts protected with L-aspartic acid, the postischemic levels of ATP and phosphocreatine were significantly higher, and the level of lactate was significantly lower than in hearts protected with L-arginine. In comparison with L-arginine, L-aspartic acid is a more efficient component of cardioplegic solution in protection of the heart from metabolic and functional damages caused by global ischemia and reperfusion.

  14. Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease.

    PubMed

    Martens, Christopher R; Kuczmarski, James M; Kim, Jahyun; Guers, John J; Harris, M Brennan; Lennon-Edwards, Shannon; Edwards, David G

    2014-08-15

    Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor l-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endothelium-dependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent ⅚ ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUN+ARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10(-9)-10(-5) M) as indicated by a reduced area under the curve (AUC; 44.56 ± 9.01 vs 100 ± 4.58, P < 0.05) and reduced maximal response (Emax; 59.9 ± 9.67 vs. 94.31 ± 1.27%, P < 0.05). AUC was not improved by ARG treatment but was significantly improved above SED animals in both RUN and RUN+ARG-treated animals. Maximal relaxation was elevated above SED in RUN+ARG animals only. l-[(3)H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUN+ARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with l-arginine. Copyright © 2014 the American Physiological Society.

  15. Deprivation of L-Arginine Induces Oxidative Stress Mediated Apoptosis in Leishmania donovani Promastigotes: Contribution of the Polyamine Pathway

    PubMed Central

    Mandal, Abhishek; Das, Sushmita; Roy, Saptarshi; Ghosh, Ayan Kumar; Sardar, Abul Hasan; Verma, Sudha; Saini, Savita; Singh, Ruby; Abhishek, Kumar; Kumar, Ajay; Mandal, Chitra; Das, Pradeep

    2016-01-01

    The growth and survival of intracellular parasites depends on the availability of extracellular nutrients. Deprivation of nutrients viz glucose or amino acid alters redox balance in mammalian cells as well as some lower organisms. To further understand the relationship, the mechanistic role of L-arginine in regulation of redox mediated survival of Leishmania donovani promastigotes was investigated. L-arginine deprivation from the culture medium was found to inhibit cell growth, reduce proliferation and increase L-arginine uptake. Relative expression of enzymes, involved in L-arginine metabolism, which leads to polyamine and trypanothione biosynthesis, were downregulated causing decreased production of polyamines in L-arginine deprived parasites and cell death. The resultant increase in reactive oxygen species (ROS), due to L-arginine deprivation, correlated with increased NADP+/NADPH ratio, decreased superoxide dismutase (SOD) level, increased lipid peroxidation and reduced thiol content. A deficiency of L-arginine triggered phosphatidyl serine externalization, a change in mitochondrial membrane potential, release of intracellular calcium and cytochrome-c. This finally led to DNA damage in Leishmania promastigotes. In summary, the growth and survival of Leishmania depends on the availability of extracellular L-arginine. In its absence the parasite undergoes ROS mediated, caspase-independent apoptosis-like cell death. Therefore, L-arginine metabolism pathway could be a probable target for controlling the growth of Leishmania parasites and disease pathogenesis. PMID:26808657

  16. L-arginine fails to prevent ventricular remodeling and heart failure in the spontaneously hypertensive rat.

    PubMed

    Brooks, Wesley W; Conrad, Chester H; Robinson, Kathleen G; Colucci, Wilson S; Bing, Oscar H L

    2009-02-01

    The effects of long-term oral administration of L-arginine, a substrate for nitric oxide (NO) production, on left ventricular (LV) remodeling, myocardial function and the prevention of heart failure (HF) was compared to the angiotensin-converting enzyme (ACE) inhibitor captopril in a rat model of hypertensive HF (aged spontaneously hypertensive rat (SHR)). SHRs and age-matched normotensive Wistar-Kyoto (WKY) rats were assigned to either no treatment, treatment with L-arginine (7.5 g/l in drinking water) or captopril (1 g/l in drinking water) beginning at 14 months of age, a time when SHRs exhibit stable compensated hypertrophy with no hemodynamic impairment; animals were studied at 23 months of age or at the time of HF. In untreated SHR, relative to WKY, there was significant LV hypertrophy, myocardial fibrosis, and isolated LV muscle performance and response to isoproterenol (ISO) were depressed; and, 7 of 10 SHRs developed HF. Captopril administration to six SHRs attenuated hypertrophy and prevented impaired inotropic responsiveness to ISO, contractile dysfunction, fibrosis, increased passive stiffness, and HF. In contrast, L-arginine administration to SHR increased LV hypertrophy and myocardial fibrosis while cardiac performance was depressed; and 7 of 9 SHRs developed HF. In WKY, L-arginine treatment but not captopril resulted in increased LV weight and the contractile response to ISO was blunted. Neither L-arginine nor captopril treatment of WKY changed fibrosis and HF did not occur. These data demonstrate that in contrast to captopril, long-term treatment with L-arginine exacerbates age-related cardiac hypertrophy, fibrosis, and did not prevent contractile dysfunction or the development of HF in aging SHR.

  17. Developmental changes of l-arginine transport at the blood-brain barrier in rats.

    PubMed

    Tachikawa, Masanori; Hirose, Shirou; Akanuma, Shin-Ichi; Matsuyama, Ryo; Hosoya, Ken-Ichi

    2018-05-01

    l-Arginine is required for regulating synapse formation/patterning and angiogenesis in the developing brain. We hypothesized that this requirement would be met by increased transporter-mediated supply across the blood-brain barrier (BBB). Thus, the purpose of this work was to test the idea that elevation of blood-to-brain l-arginine transport across the BBB in the postnatal period coincides with up-regulation of cationic acid transporter 1 (CAT1) expression in developing brain capillaries. We found that the apparent brain-to-plasma concentration ratio (Kp, app) of l-arginine after intravenous administration during the first and second postnatal weeks was 2-fold greater than that at the adult stage. Kp, app of l-serine was also increased at the first postnatal week. In contrast, Kp, app of d-mannitol, a passively BBB-permeable molecule, did not change, indicating that increased transport of l-arginine and l-serine is not due to BBB immaturity. Double immunohistochemical staining of CAT1 and a marker protein, glucose transporter 1, revealed that CAT1 was localized on both luminal and abluminal membranes of brain capillary endothelial cells during the developmental and adult stages. A dramatic increase in CAT1 expression in the brain was seen at postnatal day 7 (P7) and day 14 (P14) and the expression subsequently decreased as the brain matured. In accordance with this, intense immunostaining of CAT1 was observed in brain capillaries at P7 and P14. These findings strongly support our hypothesis and suggest that the supply of blood-born l-arginine to the brain via CAT1 at the BBB plays a key role in meeting the elevated demand for l-arginine in postnatal brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Effects of exercise and L-arginine on ventricular remodeling and oxidative stress.

    PubMed

    Xu, Xiaohua; Zhao, Weiyan; Lao, Shunhua; Wilson, Bryan S; Erikson, John M; Zhang, John Q

    2010-02-01

    Our aim was to characterize the changes in messenger RNA (mRNA) abundance, protein, and activity levels of the enzymatic antioxidants, superoxide dismutase (SOD), glutathione peroxidase, and catalase by exercise training combined with L-arginine after myocardial infarction (MI). L-Arginine (1 g x kg(-1) x d(-1)) and N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg x kg(-1) x d(-1)) were administered in drinking water for 8 wk. Sprague-Dawley rats were randomized to the following groups: sham-operated control (Sham); MI sedentary (Sed); MI exercise (Ex); MI sedentary + L-arginine (Sed + LA); MI exercise + L-arginine (Ex + LA); MI sedentary + L-NAME (Sed + L-NAME); and MI exercise + L-NAME (Ex + L-NAME). The glutathione peroxidase, catalase, and gp91(phox) mRNA levels were comparable among all the groups. The SOD mRNA level was significantly increased in the Ex group (5.43 +/- 0.87) compared with the Sed group (1.74 +/- 0.29), whereas this effect was pronouncedly down-regulated by the L-NAME intervention (2.51 +/- 1.17, P < 0.05). The protein levels of SOD in the Sed and Ex groups were both significantly decreased with the administration of L-NAME. The protein levels of catalase were significantly higher in the Ex and Ex + LA groups than that in the Sed, Sed + LA, and L-NAME-treated groups. The collagen volume fraction was significantly lowered by the exercise and/or L-arginine treatment when compared with the Sed group. Fractional shortening was significantly preserved in the trained groups compared with their corresponding sedentary groups with or without drug treatments. However, the beneficial effect was not further improved by L-arginine treatment. Our results suggest that exercise training exerts antioxidative effects and attenuates myocardial fibrosis in the MI rats. These improvements, in turn, alleviate cardiac stiffness and preserve post-MI cardiac function. In addition, L-arginine appears to have no additive effect on cardiac function or expression of

  19. Does pharmaconutrition with L-arginine and/or alpha-tocopherol improve the gut barrier in bile duct ligated rats?

    PubMed

    Tuncyurek, P; Sari, M; Firat, O; Mutaf, I; Gulter, C; Tunger, A; Yuce, G; Yilmaz, M; Makay, O; Dayangac, M; Ersin, S

    2006-01-01

    Nitric oxide supplementation and antioxidant therapy modulate gut barrier function, but the relationships between enhanced nitric oxide production, antioxidant administration, and biliary obstruction remain unclear. We evaluated the role of nitric oxide and alpha-tocopherol supplementation in bile duct ligated rats. Fifty male Wistar albino rats underwent sham operation (group I; control animals) or bile duct ligation (groups II, III, IV, and V). The ligation groups received the following regimens: standard pellet diet (group II), pellet diet plus intramuscularly administered alpha-tocopherol (group III), and L-arginine-enriched pellet diet without (group IV) or with (group V) alpha-tocopherol. Nitric oxide, malondialdehyde, and alpha-tocopherol concentrations were assessed at the end of 3 weeks. Liver and intestinal samples were scored histologically. Mesenteric lymph node and liver cultures were assessed for bacterial translocation. The liver malondialdehyde concentration was highest in group III. The nitric oxide content in the liver was higher in groups III and V, as were the blood alpha-tocopherol levels. Bacterial translocation was evident following bile duct ligation, but did not differ among the treatment groups. Intestinal histology revealed that group III had the lowest villus height, that group V had the least villus count, and that group II had the highest mucous cell count. The fibrosis scores were higher in groups IV and V. An obvious effect of alpha-tocopherol (with or without L-arginine) on the gut barrier could not be demonstrated. Moreover, the L-arginine-enriched diet promoted fibrosis in the liver. Thus, while biliary duct obstruction triggers bacterial translocation, nitric oxide and/or alpha-tocopherol supplementation did not seem to improve the gut barrier in our model. Copyright 2006 S. Karger AG, Basel.

  20. Effects of l-arginine pretreatment on nitric oxide metabolism and hepatosplanchnic perfusion during porcine endotoxemia1234

    PubMed Central

    Bruins, Maaike J; Kessels, Fons; Luiking, Yvette C; Lamers, Wouter H; Deutz, Nicolaas EP

    2011-01-01

    Background: Sepsis is accompanied by an increased need for and a decreased supply of arginine, reflecting a condition of arginine deficiency. Objective: The objective was to evaluate the effects of l-arginine pretreatment on arginine–nitric oxide (NO) production and hepatosplanchnic perfusion during subsequent endotoxemia. Design: In a randomized controlled trial, pigs (20–25 kg) received 3 μg ⋅ kg−1 ⋅ min−1 lipopolysaccharide (LPS; 5 endotoxin units/ng) intravenously and saline resuscitation. l-Arginine (n = 8; 5.3 μmol ⋅ kg−1 ⋅ min−1) or saline (n = 8) was infused starting 12 h before LPS infusion and continued for 24 h after the endotoxin infusion ended. Whole-body appearance rates, portal-drained viscera (PDV), and liver fluxes of arginine, citrulline, NO, and arginine de novo synthesis were measured by using stable-isotope infusion of [15N2]arginine and [13C-2H2]citrulline. Hepatosplanchnic perfusion was assessed by using a primed continuous infusion of para-aminohippuric acid and jejunal intramucosal partial pressure of carbon dioxide and was related to systemic hemodynamics. Results: Arginine supplementation before LPS increased whole-body NO production in the PDV but not in the liver. Furthermore, it increased blood flow in the portal vein but not in the aorta and hepatic artery. During endotoxin infusion, arginine pretreatment was associated with an increased whole-body arginine appearance and NO production in the gut. Additional effects included a preserved mean arterial pressure, the prevention of an increase in pulmonary arterial pressure, an attenuated metabolic acidosis, and an attenuated increase in the intramucosal partial pressure of carbon dioxide. Conclusion: Arginine treatment starting before endotoxemia appears to be beneficial because it improves hepatosplanchnic perfusion and oxygenation during prolonged endotoxemia, probably through an enhancement in NO synthesis, without causing deleterious systemic side effects. PMID

  1. Erythrocytes L-arginine y+ transporter inhibition by N-ethylmaleimide in ice-bath.

    PubMed

    Pinheiro da Costa, Bartira Ercília; de Almeida, Priscilla Barcellos; Conceição, Ioná Rosine; Antonello, Ivan Carlos Ferreira; d'Avila, Domingos O; Poli-de-Figueiredo, Carlos Eduardo

    2010-11-01

    Erythrocytes L: -arginine uptake is conveyed by y+ and y+L membrane transport systems. Pre-incubation with N-ethylmaleimide for 10 min at 37°C inhibits the y+ system. The aim of this study was to determine the ideal pre-incubation temperature in evaluating y+ and y+L systems. Cells were pre-incubated with or without N-ethylmaleimide for 10 min at 4°C and 37°C. L: -Arginine uptake was quantified by radioisotope and standard erythrocytes membrane flux methodology. Results demonstrate that erythrocytes L: -arginine content is depleted by pre-incubation at 37°C for 10 min, thus changing the V (max) measurement. The inhibitory effect of N-ethylmaleimide pre-incubation was temperature independent and already complete after 1 min of incubation. No significant difference in kinetic parameters was detected between cells pre-incubated at 37°C or 4°C, under zero-trans conditions. In conclusion, we suggest that measurement of erythrocytes L: -arginine uptake by y+ and y+L systems could be carried out without N-ethylmaleimide pre-incubation at 37°C.

  2. L-arginine enhances immunity to parasitoids in Drosophila melanogaster and increases NO production in lamellocytes.

    PubMed

    Kraaijeveld, Alex R; Elrayes, Naji P; Schuppe, Hansjürgen; Newland, Philip L

    2011-08-01

    Drosophila melanogaster was used as a model system to explore the link between nutrition and immunity, and to investigate the role of nitric oxide (NO) in enhancing immunity following dietary enhancement with L-arginine. First, we show that adding L-arginine to the food medium increases the ability of D. melanogaster larvae to encapsulate the eggs of the parasitoid Asobara tabida. Secondly, we show that the increase in immunity is specific to L-arginine, and not to an enhanced calorific content, and that immunity decreases when larvae are fed food with added L-NAME, an inhibitor of nitric oxide synthase. Finally, we show that parasitised larvae fed L-arginine have increased haemocyte numbers, and that the lamellocytes (haemocytes which play a key role in encapsulation) show evidence of an increased production of NO. These results suggest that NO plays a key role in immunity and that the effect of NO is mostly targeted via the lamellocytes. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Mechanisms for Improved Hygroscopicity of L-Arginine Valproate Revealed by X-Ray Single Crystal Structure Analysis.

    PubMed

    Ito, Masataka; Nambu, Kaori; Sakon, Aya; Uekusa, Hidehiro; Yonemochi, Etsuo; Noguchi, Shuji; Terada, Katsuhide

    2017-03-01

    Valproic acid is widely used as an antiepileptic agent. Valproic acid is in liquid phase while sodium valproate is in solid phase at room temperature. Sodium valproate is hard to manufacture because of its hygroscopic and deliquescent properties. To improve these, cocrystal and salt screening for valproic acid was employed in this study. Two solid salt forms, l-arginine valproate and l-lysine valproate, were obtained and characterized. By using dynamic vapor sorption method, the critical relative humidity of sodium valproate, l-arginine valproate, and l-lysine valproate were measured. Critical relative humidity of sodium valproate was 40%, of l-lysine valproate was 60%, and of l-arginine valproate was 70%. Single-crystal X-ray structure determination of l-arginine valproate was employed. l-Lysine valproate was of low diffraction quality, and l-arginine valproate formed a 1:1 salt. Crystal l-arginine valproate has a disorder in the methylene carbon chain that creates 2 conformations. The carboxylate group of valproic acid is connected to the amino group of l-arginine. Crystalline morphologies were calculated from its crystal structure. Adsorption of water molecules to crystal facets was simulated by Material Studio. When comparing adsorption energy per site of these salts, sodium valproate is more capable of adsorption of water molecule than l-arginine valproate. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  4. The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice. The effect of N(G)-nitro-L-arginine methyl ester and L-arginine.

    PubMed

    Boban-Blagaic, Alenka; Blagaic, Vladimir; Romic, Zeljko; Jelovac, Nikola; Dodig, Goran; Rucman, Rudolf; Petek, Marijan; Turkovic, Branko; Seiwerth, Sven; Sikiric, Predrag

    2006-01-01

    Alcohol disturbances, NO stimulation (by the NO-precursor L-arginine), and/or NO-synthesis blockade (by N(G)-nitro-L-arginine methyl ester, i.e. L-NAME) were challenged with stable gastric pentadecapeptide BPC 157, which inhibits both acute alcohol intoxication and alcohol withdrawal symptoms. Mice received intraperitoneally (i.p.) BPC 157 (10 microg/kg), L-NAME (10 mg/kg), and L-arginine (400 mg/kg), alone or in combination, 5 minutes before or after acute ethanol (4 g/kg i.p.) intoxication or after 0, 3, or 7 hours of withdrawal after drinking 20% alcohol for 13 days. BPC 157 rapidly opposes the strongest disturbance presentations in acute intoxication (sustained ethanol anesthesia, complete loss of righting reflex, no reaction to external stimuli, hypothermia, 25% mortality) and withdrawal (prominent seizures). NO-agents: Aggravation of acute alcohol intoxication and opposition to withdrawal are common, but the later intervals affected by L-arginine and the action throughout the experiment by L-NAME are distinctive. Given together, L-arginine and L-NAME counteract each other, while either the "L-NAME presentation" (acute intoxication) or the "L-arginine presentation" (withdrawal) predominates. BPC157+NO-agent: In acute intoxication (L-NAME predominating in NO-system functioning to aggravate intoxication), both BPC157+L-NAME and BPC157+L-arginine follow the presentation of L-NAME, but without worsened mortality. In withdrawal (L-arginine predominating in NO-system functioning to oppose disturbance symptoms), BPC157+L-NAME follows the presentation of L-NAME, while BPC 157+L-arginine imitates that of L-arginine. The relationships among pentadecapeptide BPC 157, the NO-system, acute alcohol intoxication, and opposed withdrawal may be important, presenting pentadecapeptide BPC 157 as a suitable alcohol antagonist.

  5. Decreased serum L-arginine and L-citrulline levels in major depression.

    PubMed

    Hess, S; Baker, G; Gyenes, G; Tsuyuki, R; Newman, S; Le Melledo, Jean-Michel

    2017-11-01

    It has been suggested that endothelial dysfunction caused by a decreased endothelial production of nitric oxide (NO) may contribute to the consistently observed increased risk of developing cardiovascular disease (CVD) in physically healthy patients suffering from major depression (MD). NO is a gas synthesized from Larginine (a conditionally essential amino acid) and oxygen by endothelial nitric oxide synthase (eNOS). The end products of NO production include both NO and L-citrulline. NO is rapidly reduced to the anions nitrite and nitrate, classically referred to as NO metabolites. Their measurement has been used as a surrogate measurement for endothelial NO production. We and others have shown decreased levels of NO metabolites in the serum of MD patients. The mechanism of this decreased production of NO by the endothelium has not yet been elucidated. The purpose of this study is to assess serum levels of L-arginine and L-citrulline in patients with MD. Levels of L-arginine and L-citrulline were measured in 35 unmedicated physically healthy MD patients and 36 healthy controls (HCs). L-arginine and L-citrulline concentrations were significantly lower in MD patients than in healthy controls (L-arginine, 73.54 + 21.53 μmol/L and 84.89 + 25.16, p = 0.04 μmol/L and L-citrulline 31.58 + 6.05 μmol/L and 35.19 + 6.85 μmol/L, p = 0.03, respectively). The decrease in L-arginine levels in MD patients is a possible explanation for the decrease in NO metabolites in MD patients and therefore may contribute, through endothelial dysfunction, to the increased CV risk associated with MD.

  6. Maternal melatonin or N-acetylcysteine therapy regulates hydrogen sulfide-generating pathway and renal transcriptome to prevent prenatal NG-Nitro-L-arginine-methyl ester (L-NAME)-induced fetal programming of hypertension in adult male offspring.

    PubMed

    Tain, You-Lin; Lee, Chien-Te; Chan, Julie Y H; Hsu, Chien-Ning

    2016-11-01

    differentially. Our results indicated that antioxidant therapy, by melatonin or N-acetylcysteine, in pregnant rats with nitric oxide deficiency can prevent programmed hypertension in male adult offspring. Early intervention with specific antioxidants that target redox imbalance in pregnancy to reprogram hypertension may well allow us to reduce the future burden of hypertension. The roles of transcriptome changes that are induced by N G -nitro-L-arginine-methyl ester in the offspring kidney require further clarification. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. L-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats.

    PubMed

    Rodríguez-Gómez, Isabel; Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

    2016-03-01

    This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P < 0.05, for each tissue and enzyme) in hyper- and hypothyroid rats, respectively. Arginase I abundance in aorta, heart, and kidney was increased (P < 0.05, for each tissue) in hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P < 0.05, for each tissue). Arginase II was augmented in aorta and kidney (P < 0.05, for each tissue) of hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P < 0.05, for all tissues) in hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P < 0.05) in hyper- and hypothyroid rats, respectively, in all organs studied. OAT and proline levels were positively modulated by thyroid hormones in liver but not in the other tissues. ADC protein levels were positively modulated by thyroid hormones in all tissues. According to these findings, thyroid hormone treatment positively modulates different l-arginine metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might

  8. l-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats

    PubMed Central

    Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

    2015-01-01

    This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P < 0.05, for each tissue and enzyme) in hyper- and hypothyroid rats, respectively. Arginase I abundance in aorta, heart, and kidney was increased (P < 0.05, for each tissue) in hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P < 0.05, for each tissue). Arginase II was augmented in aorta and kidney (P < 0.05, for each tissue) of hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P < 0.05, for all tissues) in hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P < 0.05) in hyper- and hypothyroid rats, respectively, in all organs studied. OAT and proline levels were positively modulated by thyroid hormones in liver but not in the other tissues. ADC protein levels were positively modulated by thyroid hormones in all tissues. According to these findings, thyroid hormone treatment positively modulates different l-arginine metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might

  9. Serum L-arginine and dimethylarginine levels in migraine patients with brain white matter lesions.

    PubMed

    Erdélyi-Bótor, Szilvia; Komáromy, Hedvig; Kamson, David Olayinka; Kovács, Norbert; Perlaki, Gábor; Orsi, Gergely; Molnár, Tihamér; Illes, Zsolt; Nagy, Lajos; Kéki, Sándor; Deli, Gabriella; Bosnyák, Edit; Trauninger, Anita; Pfund, Zoltán

    2017-05-01

    Background/Aim Migraine is a risk factor for the formation of silent brain white matter lesions (WMLs) that are possibly ischemic in nature. Although dysfunction of the L-arginine/nitric oxide (NO) pathway has been associated with oxidative stress and endothelial dysfunction in migraine, its role in WML development has not been specifically investigated. Thus, this prospective study aimed to measure the serum concentrations of the NO substrate L-arginine, the NO synthase inhibitor asymmetric dimethylarginine (ADMA), and the L-arginine transport regulator symmetric dimethylarginine (SDMA) in migraine patients in a headache-free period. Methods All participants underwent MR imaging to assess for the presence of WMLs on fluid-attenuated inversion recovery imaging. Altogether 109 migraine patients (43 with lesions, 66 without lesions) and 46 control individuals were studied. High-performance liquid chromatography was used to quantify L-arginine, ADMA and SDMA serum concentrations. Migraine characteristics were investigated, and participants were screened for risk factors that can lead to elevated serum ADMA levels independent of migraine. Results Migraine patients and controls did not differ in regard to vascular risk factors. Migraineurs with WMLs had a longer disease duration ( p < 0.001) and a higher number of lifetime headache attacks ( p = 0.005) than lesion-free patients. Higher L-arginine serum levels were found in both migraine subgroups compared to controls ( p < 0.001). Migraine patients with WMLs showed higher ADMA concentrations than lesion-free patients and controls ( p < 0.001, for both). In migraineurs, the presence of WMLs, aura and increasing age proved to be significant predictors of increased ADMA levels ( p = 0.008, 0.047 and 0.012, respectively). SDMA serum levels of lesional migraineurs were higher than in nonlesional patients ( p < 0.001). The presence of lesions and increasing age indicated an increased SDMA level ( p

  10. Augmented endothelial l-arginine transport ameliorates pressure-overload-induced cardiac hypertrophy.

    PubMed

    Rajapakse, Niwanthi W; Johnston, Tamara; Kiriazis, Helen; Chin-Dusting, Jaye P; Du, Xiao-Jun; Kaye, David M

    2015-07-01

    What is the central question of this study? What is the potential role of endothelial NO production via overexpression of the l-arginine transporter, CAT1, as a mitigator of cardiac hypertrophy? What is the main finding and its importance? Augmentation of endothelium-specific l-arginine transport via CAT1 can attenuate pressure-overload-dependent cardiac hypertrophy and fibrosis. Our findings support the conclusion that interventions that improve endothelial l-arginine transport may provide therapeutic utility in the setting of myocardial hypertrophy. Such modifications may be introduced by exercise training or locally delivered gene therapy, but further experimental and clinical studies are required. Endothelial dysfunction has been postulated to play a central role in the development of cardiac hypertrophy, probably as a result of reduced NO bioavailability. We tested the hypothesis that increased endothelial NO production, mediated by increased l-arginine transport, could attenuate pressure-overload-induced cardiac hypertrophy. Echocardiography and blood pressure measurements were performed 15 weeks after transverse aortic constriction (TAC) in wild-type (WT) mice (n = 12) and in mice with endothelium-specific overexpression of the l-arginine transporter, CAT1 (CAT+; n = 12). Transverse aortic constriction induced greater increases in heart weight to body weight ratio in WT (by 47%) than CAT+ mice (by 25%) compared with the respective controls (P ≤ 0.05). Likewise, the increase in left ventricular wall thickness induced by TAC was significantly attenuated in CAT+ mice (P = 0.05). Cardiac collagen type I mRNA expression was greater in WT mice with TAC (by 22%; P = 0.03), but not in CAT+ mice with TAC, compared with the respective controls. Transverse aortic constriction also induced lesser increases in β-myosin heavy chain mRNA expression in CAT+ mice compared with WT (P ≤ 0.05). Left ventricular systolic pressure after TAC was 36 and 39% greater in WT and

  11. Excess L-arginine restores endothelium-dependent relaxation impaired by monocrotaline pyrrole

    SciTech Connect

    Cheng Wei; Oike, Masahiro; Hirakawa, Masakazu

    2005-09-15

    The pyrrolizidine alkaloid plant toxin monocrotaline pyrrole (MCTP) causes pulmonary hypertension in experimental animals. The present study aimed to examine the effects of MCTP on the endothelium-dependent relaxation. We constructed an in vitro disease model of pulmonary hypertension by overlaying MCTP-treated bovine pulmonary artery endothelial cells (CPAEs) onto pulmonary artery smooth muscle cell-embedded collagen gel lattice. Acetylcholine (Ach) induced a relaxation of the control CPAEs-overlaid gels that were pre-contracted with noradrenaline, and the relaxation was inhibited by L-NAME, an inhibitor of NO synthase (NOS). In contrast, when MCTP-treated CPAEs were overlaid, the pre-contracted gels did not show a relaxation inmore » response to Ach in the presence of 0.5 mM L-arginine. Expression of endothelial NOS protein, Ach-induced Ca{sup 2+} transients and cellular uptake of L-[{sup 3}H]arginine were significantly smaller in MCTP-treated CPAEs than in control cells, indicating that these changes were responsible for the impaired NO production in MCTP-treated CPAEs. Since cellular uptake of L-[{sup 3}H]arginine linearly increased according to its extracellular concentration, we hypothesized that the excess concentration of extracellular L-arginine might restore NO production in MCTP-treated CPAEs. As expected, in the presence of 10 mM L-arginine, Ach showed a relaxation of the MCTP-treated CPAEs-overlaid gels. These results indicate that the impaired NO production in damaged endothelial cells can be reversed by supplying excess L-arginine.« less

  12. Mitochondrial dysfunction in brain cortex mitochondria of STZ-diabetic rats: effect of l-Arginine.

    PubMed

    Ortiz, M Del Carmen; Lores-Arnaiz, Silvia; Albertoni Borghese, M Florencia; Balonga, Sabrina; Lavagna, Agustina; Filipuzzi, Ana Laura; Cicerchia, Daniela; Majowicz, Monica; Bustamante, Juanita

    2013-12-01

    Mitochondrial dysfunction has been implicated in many diseases, including diabetes. It is well known that oxygen free radical species are produced endogenously by mitochondria, and also nitric oxide (NO) by nitric oxide synthases (NOS) associated to mitochondrial membranes, in consequence these organelles constitute main targets for oxidative damage. The aim of this study was to analyze mitochondrial physiology and NO production in brain cortex mitochondria of streptozotocin (STZ) diabetic rats in an early stage of diabetes and the potential effect of L-arginine administration. The diabetic condition was characterized by a clear hyperglycaemic state with loose of body weight after 4 days of STZ injection. This hyperglycaemic state was associated with mitochondrial dysfunction that was evident by an impairment of the respiratory activity, increased production of superoxide anion and a clear mitochondrial depolarization. In addition, the alteration in mitochondrial physiology was associated with a significant decrease in both NO production and nitric oxide synthase type I (NOS I) expression associated to the mitochondrial membranes. An increased level of thiobarbituric acid-reactive substances (TBARS) in brain cortex homogenates from STZ-diabetic rats indicated the presence of lipid peroxidation. L-arginine treatment to diabetic rats did not change blood glucose levels but significantly ameliorated the oxidative stress evidenced by lower TBARS and a lower level of superoxide anion. This effect was paralleled by improvement of mitochondrial respiratory function and a partial mitochondrial repolarization.In addition, the administration of L-arginine to diabetic rats prevented the decrease in NO production and NOSI expression. These results could indicate that exogenously administered L-arginine may have beneficial effects on mitochondrial function, oxidative stress and NO production in brain cortex mitochondria of STZ-diabetic rats.

  13. L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome

    PubMed Central

    Rodan, Lance H.; Wells, Greg D.; Banks, Laura; Thompson, Sara; Schneiderman, Jane E.; Tein, Ingrid

    2015-01-01

    Objective To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by 31Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. Methods We performed a case control study in 3 MELAS siblings (m.3243A>G tRNAleu(UUR) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO2peak) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. Results At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 31P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg2+ (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO2peak. On 31P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. Significance These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Classification of Evidence Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. Trial Registration ClinicalTrials.gov NCT01603446. PMID:25993630

  14. L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes) Syndrome.

    PubMed

    Rodan, Lance H; Wells, Greg D; Banks, Laura; Thompson, Sara; Schneiderman, Jane E; Tein, Ingrid

    2015-01-01

    To study the effects of L-arginine (L-Arg) on total body aerobic capacity and muscle metabolism as assessed by (31)Phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS) in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes) syndrome. We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR)) in MTTL1 gene) with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak)) using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine. At baseline (no L-Arg), MELAS had lower serum Arg (p = 0.001). On 3(1)P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr) (p = 0.05), decreased ATP (p = 0.018), and decreased intracellular Mg(2+) (p = 0.0002) when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1) increase in mean % maximum work at anaerobic threshold (AT) (2) increase in % maximum heart rate at AT (3) small increase in VO(2peak). On (31)P-MRS the following mean trends were noted: (1) A blunted decrease in pH after exercise (less acidosis) (2) increase in Pi/PCr ratio (ADP) suggesting increased work capacity (3) a faster half time of PCr recovery (marker of mitochondrial activity) following 5 minutes of moderate intensity exercise (4) increase in torque. These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study. Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects. ClinicalTrials.gov NCT01603446.

  15. l-Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms.

    PubMed

    He, Jinzhi; Hwang, Geelsu; Liu, Yuan; Gao, Lizeng; Kilpatrick-Liverman, LaTonya; Santarpia, Peter; Zhou, Xuedong; Koo, Hyun

    2016-10-01

    l-Arginine, a ubiquitous amino acid in human saliva, serves as a substrate for alkali production by arginolytic bacteria. Recently, exogenous l-arginine has been shown to enhance the alkalinogenic potential of oral biofilm and destabilize its microbial community, which might help control dental caries. However, l-arginine exposure may inflict additional changes in the biofilm milieu when bacteria are growing under cariogenic conditions. Here, we investigated how exogenous l-arginine modulates biofilm development using a mixed-species model containing both cariogenic (Streptococcus mutans) and arginolytic (Streptococcus gordonii) bacteria in the presence of sucrose. We observed that 1.5% (wt/vol) l-arginine (also a clinically effective concentration) exposure suppressed the outgrowth of S. mutans, favored S. gordonii dominance, and maintained Actinomyces naeslundii growth within biofilms (versus vehicle control). In parallel, topical l-arginine treatments substantially reduced the amounts of insoluble exopolysaccharides (EPS) by >3-fold, which significantly altered the three-dimensional (3D) architecture of the biofilm. Intriguingly, l-arginine repressed S. mutans genes associated with insoluble EPS (gtfB) and bacteriocin (SMU.150) production, while spxB expression (H2O2 production) by S. gordonii increased sharply during biofilm development, which resulted in higher H2O2 levels in arginine-treated biofilms. These modifications resulted in a markedly defective EPS matrix and areas devoid of any bacterial clusters (microcolonies) on the apatitic surface, while the in situ pH values at the biofilm-apatite interface were nearly one unit higher in arginine-treated biofilms (versus the vehicle control). Our data reveal new biological properties of l-arginine that impact biofilm matrix assembly and the dynamic microbial interactions associated with pathogenic biofilm development, indicating the multiaction potency of this promising biofilm disruptor. Dental caries is one

  16. l-Arginine Modifies the Exopolysaccharide Matrix and Thwarts Streptococcus mutans Outgrowth within Mixed-Species Oral Biofilms

    PubMed Central

    He, Jinzhi; Hwang, Geelsu; Liu, Yuan; Gao, Lizeng; Kilpatrick-Liverman, LaTonya; Santarpia, Peter; Zhou, Xuedong

    2016-01-01

    ABSTRACT l-Arginine, a ubiquitous amino acid in human saliva, serves as a substrate for alkali production by arginolytic bacteria. Recently, exogenous l-arginine has been shown to enhance the alkalinogenic potential of oral biofilm and destabilize its microbial community, which might help control dental caries. However, l-arginine exposure may inflict additional changes in the biofilm milieu when bacteria are growing under cariogenic conditions. Here, we investigated how exogenous l-arginine modulates biofilm development using a mixed-species model containing both cariogenic (Streptococcus mutans) and arginolytic (Streptococcus gordonii) bacteria in the presence of sucrose. We observed that 1.5% (wt/vol) l-arginine (also a clinically effective concentration) exposure suppressed the outgrowth of S. mutans, favored S. gordonii dominance, and maintained Actinomyces naeslundii growth within biofilms (versus vehicle control). In parallel, topical l-arginine treatments substantially reduced the amounts of insoluble exopolysaccharides (EPS) by >3-fold, which significantly altered the three-dimensional (3D) architecture of the biofilm. Intriguingly, l-arginine repressed S. mutans genes associated with insoluble EPS (gtfB) and bacteriocin (SMU.150) production, while spxB expression (H2O2 production) by S. gordonii increased sharply during biofilm development, which resulted in higher H2O2 levels in arginine-treated biofilms. These modifications resulted in a markedly defective EPS matrix and areas devoid of any bacterial clusters (microcolonies) on the apatitic surface, while the in situ pH values at the biofilm-apatite interface were nearly one unit higher in arginine-treated biofilms (versus the vehicle control). Our data reveal new biological properties of l-arginine that impact biofilm matrix assembly and the dynamic microbial interactions associated with pathogenic biofilm development, indicating the multiaction potency of this promising biofilm disruptor. IMPORTANCE

  17. Vasodilatory effect of L-arginine on isolated rabbit and human posterior ciliary arteries in vitro and increased optic disc blood flow in vivo.

    PubMed

    Chuman, Hideki; Sugimoto, Takako; Nao-I, Nobuhisa

    2017-12-01

    This study aimed to clarify the vasodilatory effect of L-arginine on isolated rabbit and human posterior ciliary arteries (PCAs) and to investigate changes in optic disc blood flow after an infusion of L-arginine in vivo. Vascular ring segments were mounted on a double myograph system. After obtaining maximal contraction following administration of high-K solution, L-arginine was administrated. Six volunteers received an intravenous drip infusion of 100 ml of L-arginine or saline. Changes in optic disc blood flow were measured by laser speckle flowgraphy. L-arginine relaxed high-K solution-induced contracted rabbit PCAs. Carboxy-PTIO (nitric oxide scavenger) and L-NAME (nitric oxide synthase inhibitor) inhibited L-arginine-induced relaxation in rabbit PCAs. After removal of the endothelium of the rabbit PCAs, L-arginine still relaxed rabbit PCAs. L-arginine relaxed human PCAs, despite the lack of nitric oxide production. In the L-arginine infusion group, the mean blur rate was significantly greater than that of the control group in vivo. L-arginine has both nitric oxide-dependent and independent vasodilatory effect on high K- induced contractions in isolated rabbit and human PCAs. L-arginine increased optic disc blood flow in vivo.

  18. L-Arginine attenuates the ethylene glycol induced urolithiasis in ininephrectomized hypertensive rats: role of KIM-1, NGAL, and NOs.

    PubMed

    Kandhare, Amit D; Patil, Mithun V K; Bodhankar, Subhash L

    2015-05-01

    Ethylene glycol (EG) exposure caused formation of calcium oxalate crystal that led to renal failure, which is associated with higher prevalence of hypertension. L-Arginine is known to have an antioxidant and nephro-protective potential. To evaluate the effect of L-arginine against EG-induced urolithiasis in uninephrectomized hypertensive rats. Uninephrectomized male Wistar rats (180-200 g) were used to induce urinary calculi through oral administration of EG (0.75%) in distilled water. Rats were treated with either distilled water (10 mg/kg, p.o.) or telmisartan (10 mg/kg, p.o.) or Cystone (500 mg/kg, p.o.) or L-arginine (250, 500, and 1000 mg/kg, p.o.) for 28 days. Various hemodynamic, biochemical, molecular, and histological parameters were assessed in kidney and heart. Rats treated with L-arginine (500 and 1000 mg/kg) significantly restored altered relative organ weight, urine output, urine density, urinary pH, and water intake. EG-induced alterations in electrocardiographic (QRS interval, HR, and ST height) and hemodynamic (SBP, DBP, MABP, and LVEDP) abnormalities were significantly restored by L-arginine (500 and 1000 mg/kg) treatment. It also significantly restored alteration in serum and urine biochemical parameters induced by EG. The elevated oxido-nitrosative stress was also significantly decreased by L-arginine (500 and 1000 mg/kg) treatment. It also significantly down-regulated EG-induced up-regulated renal KIM-1, NGAL, eNOS, and iNOs mRNA expressions. Histological aberrations induced in the renal and cardiac tissues were also ameliorated by l-arginine treatment. L-Arginine exerts its nephro- and cardio-protective potential in EG-induced urolithiasis in uninephrectomized hypertensive rats via modulation of KIM-1, NGAL, eNOS, and iNOs mRNA expression.

  19. Mature coconut water exhibits antidiabetic and antithrombotic potential via L-arginine-nitric oxide pathway in alloxan induced diabetic rats.

    PubMed

    Preetha, Prabhakaran Prabha; Devi, Vishalakshiamma Girija; Rajamohan, Thankappan

    2015-11-01

    The aims of the present study were to assess whether the antidiabetic activity of mature coconut water (MCW) is mediated through L-arginine-nitric oxide pathway in diabetic rats, and to study the effects of MCW on blood coagulation. Diabetes was induced in male Sprague-Dawley rats by injecting them with alloxan (150 mg/kg body weight). MCW (4 mL/100 g body weight) and L-arginine (7.5 mg/100 g body weight) was given orally for 45 days. L-NAME was given at a dose of 0.5 mg/kg body weight. Concentrations of blood glucose, plasma insulin, glycosylated hemoglobin (HbA1c), L-arginine, urine volume and urinary creatinine levels, activity of nitric oxide synthase (NOS), and arginase as well as the abnormalities in hemostasis and thrombosis were measured in all the experimental groups. Treatment with MCW and L-arginine reduced the concentration of blood glucose and HbA1c in diabetic rats. MCW and L-arginine treatment exhibited significant antithrombotic activity in diabetic rats, which was evident from the reduced levels of WBC, platelets, fibrin, and fibrinogen. MCW and L-arginine treatment prolonged the prothrombin time in diabetic rats and reduced the activity of Factor V. In addition to this, the activity of nitric oxide synthase, liver and plasma arginine content, and urinary nitrite were higher in MCW-treated diabetic rats whereas L-NAME treatment inhibited the beneficial effects induced by MCW and arginine. The results clearly indicate that L-arginine is a major factor responsible for the antidiabetic and antithrombotic potential of coconut water, and is mediated through the L-arginine-nitric oxide pathway.

  20. Microhardness study of the nonlinear optical crystal L-arginine hydrochloride monohydrate

    NASA Astrophysics Data System (ADS)

    Mukerji, Sudeshna; Kar, Tanusree

    2000-12-01

    The results of measurement of the Vickers microhardness ( H v ) of the (100), (010), and (001) faces of the nonlinear optical (NLO) crystal L-arginine hydrochloride monohydrate (LAHCl) have been reported. It was observed that the microhardnesses of the three crystal planes decrease with the increase of applied load, and the hardness profile is different for different planes. The proportional specimen-resistance (PSR) model of Li and Bradt is used to explain the microhardness behavior of LAHCl. The indentation work-hardening coefficients ( n) for three planes were found to be greater than 1.8, and this indicates that LAHCl is a soft crystal.

  1. Activated Macrophages Destroy Intracellular Leishmania Major Amastigotes by an l-Arginine-Dependent Killing Mechanism

    DTIC Science & Technology

    1990-01-01

    atom of L-arginine and a precursor of the nitrite measured, may disrupt Fe- dependent enzymatic pathways vital to the survival of amastigotes within...geneti- a precursor of the nitrite measured, may disrupt Fe- cally susceptible BALB/c mice. The exact role of IFN-1 in dependent enzymatic pathways vital...induces the heme - dependent activation of 0 6 ± 4 89 80 guanylate cyclase. with the subsequent stimulation of 0.01 8 ± 3 85 67 the secondary messenger

  2. Histological and immunohistochemical effects of L-arginine and silymarin on TNBS-induced inflammatory bowel disease in rats.

    PubMed

    Al-Drees, Abdul; Khalil, Mahmoud Salah

    2016-11-01

    Inflammatory bowel disease (IBD) is a chronic disease that affects quality of life. Various mediators are involved in IBD pathogenesis including inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB), cytochrome c, heat shock protein 70 (HSP70) and tumor necrosis factor (TNF)-α. L-Arginine (L-Arg) can be depleted in IBD, and silymarin inhibits neutrophil infiltration, NF-κB, and TNF-α, which have crucial roles in inducing IBD. This study aimed to investigate whether silymarin and L-Arg supplementation decreases IBD progression in trinitrobenzine-sulfonic acid (TNBS)-induced colitis. Fifty adult male albino rats were randomized into five groups (10 animals per group): Group I rats orally received 100 mg silymarin/kg body weight once daily; Group II rats orally received 2 mg L-Arg/100 g body weight in 5 mL distilled water once daily; Group III rats rectally received 0.85 mL TNBS in 50% ethanol to induce colitis; Group IV rats were treated similar to group III and, on recovery from anesthesia, received silymarin as described for group I; and Group V rats were treated similar to group III and, on recovery from anesthesia, received L-Arg as described for group II. On day 7, the rats were anesthetized, and blood samples were collected to determine the serum concentrations of TNF-α. Laparotomy and total colectomy were performed for macroscopic, histological, and immunohistochemical investigations. The results showed that silymarin and L-Arg macroscopically and microscopically ameliorated TNBS-induced colitis; significantly decreased the serum levels of TNF-α; inhibited the colonic expression of iNOS, NF-κB, and cytochrome c; and increased expression of HSP70. Our results suggest that these complementary medicines could be used to supplement current treatments for IBD.

  3. Effects of L-arginine on solubilization and purification of plant membrane proteins.

    PubMed

    Arakawa, Junji; Uegaki, Masamichi; Ishimizu, Takeshi

    2011-11-01

    Biochemical analysis of membrane proteins is problematic at the level of solubilization and/or purification because of their hydrophobic nature. Here, we developed methods for efficient solubilization and purification of membrane proteins using L-arginine. The addition of 100 mM of basic amino acids (L-arginine, L-lysine, and L-ornithine) to a detergent-containing solubilization buffer enhanced solubilization (by 2.6-4.3 fold) of a model membrane protein-polygalacturonic acid synthase. Of all the amino acids, arginine was the most effective additive for solubilization of this membrane protein. Arginine addition also resulted in the best solubilization of other plant membrane proteins. Next, we examined the effects of arginine on purification of a model membrane protein. In anion-exchange chromatography, the addition of arginine to the loading and elution buffers resulted in a greater recovery of a membrane protein. In ultrafiltration, the addition of arginine to a protein solution significantly improved the recovery of a membrane protein. These results were thought to be due to the properties of arginine that prevent aggregation of hydrophobic proteins. Taken together, the results of our study showed that arginine is useful for solubilization and purification of aggregate-prone membrane proteins. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Hypercholesterolemia enhances thromboembolism in arterioles but not venules: complete reversal by L-arginine.

    PubMed

    Broeders, Martijn A W; Tangelder, Geert Jan; Slaaf, Dick W; Reneman, Robert S; oude Egbrink, Mirjam G A

    2002-04-01

    We investigated in vivo the effect of cholesterol diet-induced hypercholesterolemia (HC) on thromboembolism in nonatherosclerotic rabbit mesenteric arterioles and venules (diameter 21 to 45 micrometer). After mechanical vessel wall injury, the ensuing thromboembolic reaction was studied by intravital videomicroscopy. A dramatic prolongation of embolization duration (median >600 seconds) was observed in the arterioles of the HC group compared with the arterioles of a normal chow-fed (NC) control group (142 seconds, P<0.0001); concomitantly, relative thrombus height increased (thrombus height/vessel diameter was 68% for the HC group and 58% for the NC group; P<0.05). By contrast, in venules, cholesterol did not affect embolization duration (42 seconds for HC group, 34 seconds for NC group) and thrombus height (66% for HC group, 64% for NC group). Furthermore, the role of endothelial NO synthesis was studied. In arterioles, stimulation of endogenous NO synthesis through mesenteric superfusion of L-arginine (1 mmol/L) completely reversed cholesterol-enhanced embolization (152 seconds) but did not influence thrombus height (63%). L-Arginine had no effect in venules of the HC group (51 seconds) and nor in the arterioles and venules of the NC group (177 seconds for arterioles, 43 seconds for venules). This study indicates that hypercholesterolemia selectively enhances thrombus formation and embolization in arterioles but not in venules and that stimulation of endogenous NO production antagonizes this enhancement of arteriolar thromboembolism.

  5. The synthesis and cell interaction of statistical L-arginine - glycine - L-aspartic acid terpolypeptides.

    PubMed

    Mbizana, Siyasanga; Hlalele, Lebohang; Pfukwa, Rueben; du Toit, Andre; Lumkwana, Dumisile; Loos, Benjamin; Klumperman, Bert

    2018-05-01

    Copolymerizations and terpolymerizations of N-carboxyanhydrides (NCAs) of glycine (Gly), Nδ-carbobenzyloxy-L-ornithine ((Z)-Orn) and β-benzyl-L-aspartate ((Bz)-Asp) were investigated. In situ 1H NMR spectroscopy was used to monitor individual comonomer consumptions during binary and ternary copolymerizations. The six relevant reactivity ratios were determined from copolymerizations of the NCAs of amino acids via nonlinear least squares curve fitting. The reactivity ratios were subsequently used to maximize the occurrence of the Asp-Gly-Orn (DGR') sequence in the terpolymers. Terpolymers with variable probability of occurrence of DGR' were prepared in the lab. Subsequently, the ornithine residues on the terpolymers were converted to L-arginine (R) residues via guanidination reaction after removal of the protecting groups. The resulting DGR terpolymers translate to traditional peptides and proteins with variable RGD content, due to the convention in nomenclature that peptides are depicted from N- to C-terminus, whereas the NCA ring-opening polymerization is conducted from C- to N-terminus. The L-arginine containing terpolymers were evaluated for cell interaction, where it was found that neuronal cells display enhanced adhesion and process formation when plated in the presence of statistical DGR terpolymers.

  6. Role of L-arginine in the biological effects of blue light

    NASA Astrophysics Data System (ADS)

    Makela, Anu M.

    2005-11-01

    Arginine, a semi-essential amino acid, and metabolites of arginine exert multiple biological effects. It has been known that arginine causes the release of various hormones such as insulin, glucagon, growth hormone, prolactin, and adrenal catecholamines. Arginine infusion also produces vasodilation, and in the kidney increased plasma flow accompanied by increases in glomerular filtration rate (GFR). Recent studies have showed that blue and red light irradiation in vitro and in vivo can increase production of nitric oxide (NO), superoxide anion, and related reactive oxygen species (ROS). These then can modulate the production and secretion of several cytokines and other mediators and play an important role as regulatory mediators in signaling processes which can then modulate the production, mobilization and homing of stem cells. It is proposed that some of the therapeutic effects of light can be considered to be due to the changes in the metabolism of L-arginine. The regulation of L-arginine turnover by the use of light at blue wavelengths between 400nm and 510nm can be the explanation for some of the observed effects of blue light: lowering of blood pressure, pain killing effect, regulating insulin production, anti-inflammatory action, and possible effects on the release and homing of stem cells.

  7. Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME

    PubMed Central

    Djakovic, Zeljko; Djakovic, Ivka; Cesarec, Vedran; Madzarac, Goran; Becejac, Tomislav; Zukanovic, Goran; Drmic, Domagoj; Batelja, Lovorka; Zenko Sever, Anita; Kolenc, Danijela; Pajtak, Alen; Knez, Nikica; Japjec, Mladen; Luetic, Kresimir; Stancic-Rokotov, Dinko; Seiwerth, Sven; Sikiric, Predrag

    2016-01-01

    AIM To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. METHODS Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NO-system. In the 4 d after esophagogastric anastomosis creation, rats received medication (/kg intraperitoneally once daily: BPC 157 (10 μg, 10 ng), L-NAME (5 mg), or L-arginine (100 mg) alone and/or combined or BPC 157 (10 μg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage (sum of the longest diameters, mm), esophagitis (scored 0-5), weak anastomosis (mL H2O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter (cm H2O), progressive weight loss (g) and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5) at the stomach surface immediately after anastomosis creation. RESULTS BPC 157 (all regimens) fully counteracted the perilous disease course from the very beginning (i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening (with L-NAME administration) and amelioration (with L-arginine), either L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or they counteract each other (L-NAME + L-arginine

  8. A relative L-arginine deficiency contributes to endothelial dysfunction across the stages of the menopausal transition.

    PubMed

    Klawitter, Jelena; Hildreth, Kerry L; Christians, Uwe; Kohrt, Wendy M; Moreau, Kerrie L

    2017-09-01

    Vascular endothelial function declines across the menopause transition in women. We tested the hypothesis that reduced availability of the endothelial nitric oxide synthase [eNOS] substrate L-arginine is an underlying mechanism to vascular endothelial dysfunction across menopause stages. Endothelial function (brachial artery flow-mediated dilation [FMD]) and plasma markers of L-arginine metabolism (citrulline, N G -mono-methyl-ւ-arginine [L-NMMA] asymmetric dimethylarginine [ADMA] and N G -N 'G -dimethyl-l-arginine [SDMA]), were measured in 129 women: 36 premenopausal (33 ± 7 years), 16 early- (49 ± 3 years) or 21 late- (50 ± 4 years) perimenopausal, and 21 early- (55 ± 3 years) or 35 late- (61 ± 4 years) postmenopausal. FMD was progressively reduced across menopause stages ( P  < 0.001). Menopause stage was associated with L-arginine concentrations ( P  = 0.012), with higher levels in early postmenopausal compared to early and late perimenopausal women ( P  < 0.05). The methylarginine and eNOS inhibitor L-NMMA was higher in early and late postmenopausal women compared to premenopausal and early and late perimenopausal women (all P  < 0.001), and was inversely correlated with FMD ( r  = -0.30, P  = 0.001). The L-arginine/L-NMMA ratio, a potential biomarker of relative L-arginine levels, was lower in postmenopausal compared to either premenopausal or perimenopausal women (both P  < 0.001), and was positively correlated with FMD ( r  = 0.33, P  < 0.001). There were no differences in plasma citrulline, ADMA or SDMA across groups. These data suggest that a relative L-arginine deficiency may be a mechanism underlying the decline in endothelial function with the menopause transition in women. The relative L-arginine deficiency may be related to elevated levels of the methylarginine L-NMMA, which would compete with L-arginine for eNOS and for intracellular transport, reducing NO biosynthesis. © 2017 The Authors. Physiological

  9. Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME.

    PubMed

    Djakovic, Zeljko; Djakovic, Ivka; Cesarec, Vedran; Madzarac, Goran; Becejac, Tomislav; Zukanovic, Goran; Drmic, Domagoj; Batelja, Lovorka; Zenko Sever, Anita; Kolenc, Danijela; Pajtak, Alen; Knez, Nikica; Japjec, Mladen; Luetic, Kresimir; Stancic-Rokotov, Dinko; Seiwerth, Sven; Sikiric, Predrag

    2016-11-07

    To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NO-system. In the 4 d after esophagogastric anastomosis creation, rats received medication (/kg intraperitoneally once daily: BPC 157 (10 μg, 10 ng), L-NAME (5 mg), or L-arginine (100 mg) alone and/or combined or BPC 157 (10 μg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage (sum of the longest diameters, mm), esophagitis (scored 0-5), weak anastomosis (mL H 2 O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter (cm H 2 O), progressive weight loss (g) and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5) at the stomach surface immediately after anastomosis creation. BPC 157 (all regimens) fully counteracted the perilous disease course from the very beginning ( i.e ., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening (with L-NAME administration) and amelioration (with L-arginine), either L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or they counteract each other (L-NAME + L-arginine); with

  10. The presence of African American race predicts improvement in coronary endothelial function after supplementary L-arginine.

    PubMed

    Houghton, Jan L; Philbin, Edward F; Strogatz, David S; Torosoff, Mikhail T; Fein, Steven A; Kuhner, Patricia A; Smith, Vivienne E; Carr, Albert A

    2002-04-17

    The purpose of our study was to determine if the presence of African American ethnicity modulates improvement in coronary vascular endothelial function after supplementary L-arginine. Endothelial dysfunction is an early stage in the development of coronary atherosclerosis and has been implicated in the pathogenesis of hypertension and cardiomyopathy. Amelioration of endothelial dysfunction has been demonstrated in patients with established coronary atherosclerosis or with risk factors in response to infusion of L-arginine, the precursor of nitric oxide. Racial and gender patterns in L-arginine responsiveness have not, heretofore, been studied. Invasive testing of coronary artery and microvascular reactivity in response to graded intracoronary infusions of acetylcholine (ACh) +/- L-arginine was carried out in 33 matched pairs of African American and white subjects with no angiographic coronary artery disease. Pairs were matched for age, gender, indexed left ventricular mass, body mass index and low-density lipoprotein cholesterol. In addition to the matching parameters, there were no significant differences in peak coronary blood flow (CBF) response to intracoronary adenosine or in the peak CBF response to ACh before L-arginine infusion. However, absolute percentile improvement in CBF response to ACh infusion after L-arginine, as compared with before, was significantly greater among African Americans as a group (45 +/- 10% vs. 4 +/- 6%, p = 0.0016) and after partitioning by gender. The mechanism of this increase was mediated through further reduction in coronary microvascular resistance. L-arginine infusion also resulted in greater epicardial dilator response after ACh among African Americans. We conclude that intracoronary infusion of L-arginine provides significantly greater augmentation of endothelium-dependent vascular relaxation in those of African American ethnicity when compared with matched white subjects drawn from a cohort electively referred for coronary

  11. Effect of Polyhydroxybutyrate (PHB) storage on L-arginine production in recombinant Corynebacterium crenatum using coenzyme regulation.

    PubMed

    Xu, Meijuan; Qin, Jingru; Rao, Zhiming; You, Hengyi; Zhang, Xian; Yang, Taowei; Wang, Xiaoyuan; Xu, Zhenghong

    2016-01-19

    Corynebacterium crenatum SYPA 5 is the industrial strain for L-arginine production. Poly-β-hydroxybutyrate (PHB) is a kind of biopolymer stored as bacterial reserve materials for carbon and energy. The introduction of the PHB synthesis pathway into several strains can regulate the global metabolic pathway. In addition, both the pathways of PHB and L-arginine biosynthesis in the cells are NADPH-dependent. NAD kinase could upregulate the NADPH concentration in the bacteria. Thus, it is interesting to investigate how both PHB and NAD kinase affect the L-arginine biosynthesis in C. crenatum SYPA 5. C. crenatum P1 containing PHB synthesis pathway was constructed and cultivated in batch fermentation for 96 h. The enzyme activities of the key enzymes were enhanced comparing to the control strain C. crenatum SYPA 5. More PHB was found in C. crenatum P1, up to 12.7 % of the dry cell weight. Higher growth level and enhanced glucose consumptions were also observed in C. crenatum P1. With respect to the yield of L-arginine, it was 38.54 ± 0.81 g/L, increasing by 20.6 %, comparing to the control under the influence of PHB accumulation. For more NADPH supply, C. crenatum P2 was constructed with overexpression of NAD kinase based on C. crenatum P1. The NADPH concentration was increased in C. crenatum P2 comparing to the control. PHB content reached 15.7 % and 41.11 ± 1.21 g/L L-arginine was obtained in C. crenatum P2, increased by 28.6 %. The transcription levels of key L-arginine synthesis genes, argB, argC, argD and argJ in recombinant C. crenatum increased 1.9-3.0 times compared with the parent strain. Accumulation of PHB by introducing PHB synthesis pathway, together with up-regulation of coenzyme level by overexpressing NAD kinase, enables the recombinant C. crenatum to serve as high-efficiency cell factories in the long-time L-arginine fermentation. Furthermore, batch cultivation of the engineered C. crenatum revealed that it could accumulate both extracellular L-arginine

  12. Growth and dielectric, mechanical, thermal and etching studies of an organic nonlinear optical L-arginine trifluoroacetate (LATF) single crystal

    SciTech Connect

    Arjunan, S.; Department of Physics, Presidency College, Chennai 600005; Mohan Kumar, R.

    2008-08-04

    L-arginine trifluoroacetate, an organic nonlinear optical material, has been synthesized from aqueous solution. Bulk single crystal of dimension 57 mm x 5 mm x 3 mm has been grown by temperature lowering technique. Powder X-ray diffraction studies confirmed the monoclinic structure of the grown L-arginine trifluoroacetate crystal. Linear optical property of the grown crystal has been studied by UV-vis spectrum. Dielectric response of the L-arginine trifluoroacetate crystal was analysed for different frequencies and temperatures in detail. Microhardness study on the sample reveals that the crystal possesses relatively higher hardness compared to many organic crystals. Thermal analyses confirmed that the L-argininemore » trifluoroacetate material is thermally stable upto 212 deg. C. The etching studies have been performed to assess the perfection of the L-arginine trifluoroacetate crystal. Kurtz powder second harmonic generation test confirms the nonlinear optical properties of the as-grown L-arginine trifluoroacetate crystal.« less

  13. Cellular transport of l-arginine determines renal medullary blood flow in control rats, but not in diabetic rats despite enhanced cellular uptake capacity.

    PubMed

    Persson, Patrik; Fasching, Angelica; Teerlink, Tom; Hansell, Peter; Palm, Fredrik

    2017-02-01

    Diabetes mellitus is associated with decreased nitric oxide bioavailability thereby affecting renal blood flow regulation. Previous reports have demonstrated that cellular uptake of l-arginine is rate limiting for nitric oxide production and that plasma l-arginine concentration is decreased in diabetes. We therefore investigated whether regional renal blood flow regulation is affected by cellular l-arginine uptake in streptozotocin-induced diabetic rats. Rats were anesthetized with thiobutabarbital, and the left kidney was exposed. Total, cortical, and medullary renal blood flow was investigated before and after renal artery infusion of increasing doses of either l-homoarginine to inhibit cellular uptake of l-arginine or N ω -nitro- l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. l-Homoarginine infusion did not affect total or cortical blood flow in any of the groups, but caused a dose-dependent reduction in medullary blood flow. l-NAME decreased total, cortical and medullary blood flow in both groups. However, the reductions in medullary blood flow in response to both l-homoarginine and l-NAME were more pronounced in the control groups compared with the diabetic groups. Isolated cortical tubular cells displayed similar l-arginine uptake capacity whereas medullary tubular cells isolated from diabetic rats had increased l-arginine uptake capacity. Diabetics had reduced l-arginine concentrations in plasma and medullary tissue but increased l-arginine concentration in cortical tissue. In conclusion, the reduced l-arginine availability in plasma and medullary tissue in diabetes results in reduced nitric oxide-mediated regulation of renal medullary hemodynamics. Cortical blood flow regulation displays less dependency on extracellular l-arginine and the upregulated cortical tissue l-arginine may protect cortical hemodynamics in diabetes. Copyright © 2017 the American Physiological Society.

  14. Genome-wide association reveals that common genetic variation in the kallikrein-kinin system is associated with serum L-arginine levels.

    PubMed

    Zhang, Weihua; Jernerén, Fredrik; Lehne, Benjamin C; Chen, Ming-Huei; Luben, Robert N; Johnston, Carole; Elshorbagy, Amany; Eppinga, Ruben N; Scott, William R; Adeyeye, Elizabeth; Scott, James; Böger, Rainer H; Khaw, Kay-Tee; van der Harst, Pim; Wareham, Nicholas J; Vasan, Ramachandran S; Chambers, John C; Refsum, Helga; Kooner, Jaspal S

    2016-11-30

    L-arginine is the essential precursor of nitric oxide, and is involved in multiple key physiological processes, including vascular and immune function. The genetic regulation of blood L-arginine levels is largely unknown. We performed a genome-wide association study (GWAS) to identify genetic factors determining serum L-arginine levels, amongst 901 Europeans and 1,394 Indian Asians. We show that common genetic variations at the KLKB1 and F12 loci are strongly associated with serum L-arginine levels. The G allele of single nucleotide polymorphism (SNP) rs71640036 (T/G) in KLKB1 is associated with lower serum L-arginine concentrations (10 µmol/l per allele copy, p=1×10 -24 ), while allele T of rs2545801 (T/C) near the F12 gene is associated with lower serum L-arginine levels (7 µmol/l per allele copy, p=7×10 -12 ). Together these two loci explain 7 % of the total variance in serum L-arginine concentrations. The associations at both loci were replicated in independent cohorts with plasma L-arginine measurements (p<0.004). The two sentinel SNPs are in nearly complete LD with the nonsynonymous SNP rs3733402 at KLKB1 and the 5'-UTR SNP rs1801020 at F12, respectively. SNPs at both loci are associated with blood pressure. Our findings provide new insight into the genetic regulation of L-arginine and its potential relationship with cardiovascular risk.

  15. Roles of export genes cgmA and lysE for the production of L-arginine and L-citrulline by Corynebacterium glutamicum.

    PubMed

    Lubitz, Dorit; Jorge, João M P; Pérez-García, Fernando; Taniguchi, Hironori; Wendisch, Volker F

    2016-10-01

    L-arginine is a semi-essential amino acid with application in cosmetic, pharmaceutical, and food industries. Metabolic engineering strategies have been applied for overproduction of L-arginine by Corynebacterium glutamicum. LysE was the only known L-arginine exporter of this bacterium. However, an L-arginine-producing strain carrying a deletion of lysE still accumulated about 10 mM L-arginine in the growth medium. Overexpression of the putative putrescine and cadaverine export permease gene cgmA was shown to compensate for the lack of lysE with regard to L-arginine export. Moreover, plasmid-borne overexpression of cgmA rescued the toxic effect caused by feeding of the dipeptide Arg-Ala to lysE-deficient C. glutamicum and argO-deficient Escherichia coli strains. Deletion of the repressor gene cgmR improved L-arginine titers by 5 %. Production of L-lysine and L-citrulline was not affected by cgmA overexpression. Taken together, CgmA may function as an export system not only for the diamine putrescine and cadaverine but also for L-arginine. The major export system for L-lysine and L-arginine LysE may also play a role in L-citrulline export since production of L-citrulline was reduced when lysE was deleted and improved by 45 % when lysE was overproduced.

  16. l-arginine:glycine amidinotransferase (AGAT) deficiency: clinical presentation and response to treatment in two patients with a novel mutation.

    PubMed

    Edvardson, Simon; Korman, Stanley H; Livne, Amir; Shaag, Avraham; Saada, Ann; Nalbandian, Ruppen; Allouche-Arnon, Hyla; Gomori, J Moshe; Katz-Brull, Rachel

    2010-01-01

    Creatine and creatine phosphate provide storage and transmission of phosphate-bound energy in muscle and brain. Of the three inborn errors of creatine metabolism causing brain creatine depletion, l-arginine:glycine amidinotransferase (AGAT) deficiency has been described in only two families. We describe clinical and biochemical features, magnetic resonance spectroscopy (MRS) findings and response to creatine supplementation in two siblings with a novel mutation in the AGAT-encoding GATM gene. The sister and brother were evaluated at age 12 and 18years, respectively, because of mild mental retardation, muscle weakness and low weight. Extensive work-up had previously yielded negative results. Electron microscopy of the muscle revealed tubular aggregates and the activity of respiratory chain complexes was decreased in the muscle. Urine organic acid concentrations normalized to urine creatinine concentration were all increased, suggesting a creatine metabolism disorder. Brain MRS was remarkable for absence of creatine. Urine guanidinoacetate levels by tandem mass spectrometry were low, suggesting AGAT deficiency. GATM sequencing revealed a homozygous single nucleotide insertion 1111_1112insA, producing a frame-shift at Met-371 and premature termination at codon 376. Eleven months after commencing treatment with oral creatine monohydrate 100mg/kg/day, repeat MRI/MRS showed significantly increased brain creatine in the sister and a slight increase in the older brother. The parents' impression of improved strength and stamina was substantiated by increased post-treatment versus pre-treatment scores in the Vineland Adaptive Behavior Scale, straight-arm raising and timed up-and-go tests. Similarly, there was an apparent improvement in cognitive function, with significantly increased IQ-scores in the sister and marginal improvement in the brother. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Protective effect of L-arginine against necrosis and apoptosis induced by experimental ischemic and reperfusion in rat liver.

    PubMed

    Chattopadhyay, Pronobesh; Shukla, Gunjan; Wahi, Arun Kumar

    2009-01-01

    To study the effect of L-arginine on apoptosis and necrosis induced by 1-h ischemia followed by 3-h reperfusion. Adult Wistar rats underwent 60 min of partial liver ischemia followed by 3-h reperfusion. Eighteen Wistar rats were divided into sham-operated control group (I) (n = 6), ischemia and reperfusion (I/R) group (0.9 % saline (5 mL/kg, orally) for 7 days) (II) (n = 6), and L-arginine-treated group (10 mg/kg body weight daily orally for 7 days before inducing ischemia-reperfusion maneuver) (III) (n = 6). Apoptotic and necrotic hepatocytes, nitric oxide levels in hepatocytes, Bcl-2 mRNA, and Bcl-2 protein were measured. Liver injury was assessed by plasma alanine transaminases (ALT), aspartate transaminases (AST), liver histopathology, and electron microscopy. An ischemic and reperfusion hepatocellular injury occurred as was indicated by increased serum ALT, AST, histopathology, and electron microscopy. Apoptosis and necrosis associated marker gene Bcl-2 mRNA and protein expression were decreased in I/R group. Pretreatment with L-arginine significantly decreased serum ALT and AST level and apoptotic and necrotic cells after 1 h ischemia followed by 3 h of reperfusion. Nitric oxide production in hepatocytes was increased twofold by L-arginine treatment when compared with I/R group. Histopathology and transmission electron microscopy (TEM) studies showed markedly diminished hepatocellular injury in L-arginine-pretreated rats during the hepatic I/R. Thus, it may be concluded that L-arginine afforded significant protection from necrosis and apoptosis in I/R injury by upregulated Bcl-2 gene and nitric oxide production.

  18. The acute effects of L-arginine on hormonal and metabolic responses during submaximal exercise in trained cyclists.

    PubMed

    Forbes, Scott C; Harber, Vicki; Bell, Gordon J

    2013-08-01

    L-arginine may enhance endurance performance mediated by two primary mechanisms including enhanced secretion of endogenous growth hormone (GH) and as a precursor of nitric oxide (NO); however, research in trained participants has been equivocal. The purpose was to investigate the effect of acute L-arginine ingestion on the hormonal and metabolic response during submaximal exercise in trained cyclists. Fifteen aerobically trained men (age: 28 ± 5 y; body mass: 77.4 ± 9.5 kg; height: 180.9 ± 7.9 cm; VO2max: 59.6 ± 5.9 ml·kg- 1·min-1) participated in a randomized, double-blind, crossover study. Subjects consumed L-arginine (ARG; 0. 075 g·kg-1 body mass) or a placebo (PLA) before performing an acute bout of submaximal exercise (60 min at 80% of power output achieved at ventilatory threshold). The ARG condition significantly increased plasma L-arginine concentrations (~146%), while no change was detected in the PLA condition. There were no differences between conditions for GH, nonesterified fatty acids (NEFA), lactate, glucose, VO2, VCO2, RER, CHO oxidation, and NOx. There was reduced fat oxidation at the start of exercise (ARG: 0.36 ± 0.25 vs. PLA: 0.42 ± 0.23 g·min-1, p < .05) and an elevated plasma glycerol concentrations at the 45-min time point (ARG: 340.3 vs. PLA: 288.5 μmol·L-1, p < .05) after L-arginine consumption. In conclusion, the acute ingestion of L-arginine did not alter any hormonal, metabolic, or cardio-respiratory responses during submaximal exercise except for a small but significant increase in glycerol at the 45-min time point and a reduction in fat oxidation at the start of exercise.

  19. Decreased Reactivity of Skin Microcirculation in Response to l-Arginine in Later-Onset Type 1 Diabetes

    PubMed Central

    Neubauer-Geryk, Jolanta; Kozera, Grzegorz M.; Wolnik, Bogumil; Szczyrba, Sebastian; Nyka, Walenty M.; Bieniaszewski, Leszek

    2013-01-01

    OBJECTIVE The aim of our study was to evaluate the vasodilatory effect of l-arginine infusion on the skin microcirculation and to assess the relationship between this effect and the presence of microangiopathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Capillaroscopy was performed before and after l-arginine infusion in 48 diabetic patients (26 women and 22 men; age, 39.8 ± 6.3 years) and 24 volunteers free of any chronic disease (13 women and 11 men; age, 38.0 ± 6.7 years). The skin microcirculation reactivity, as expressed by the percentage of area covered by capillaries (coverage) and the distance between capillaries (distance), and the relationship between microcirculation reactivity and the presence of microangiopathic complications were assessed. RESULTS The distance before l-arginine infusion was significantly lower in patients than in controls (221 [153–311] vs. 240 [185–356] µm; P = 0.02) and did not differ after l-arginine infusion (223.5 [127–318] vs. 242.5 [181–341] µm; P = 0.27). The difference between the coverage values obtained before and after l-arginine infusion (Δcoverage) was significantly different from zero in the control group but not in the diabetes group. Patients with later onset of diabetes were characterized by decreased skin microcirculation reactivity when compared with patients with earlier onset of diabetes (−1.18 [−5.07 to 11.60] vs. 1.36 [−6.00 to 8.06]; P = 0.02) despite the higher prevalence of retinopathy in patients with earlier onset of diabetes (64% vs. 26%; P = 0.02). CONCLUSIONS Skin microvascular reactivity is impaired in patients with later onset of type 1 diabetes. Capillaroscopy with l-arginine infusion is useful for the identification of skin microangiopathy in type 1 diabetes. PMID:23150282

  20. Cationic amino acid transporter 1-mediated L-arginine transport at the inner blood-retinal barrier.

    PubMed

    Tomi, Masatoshi; Kitade, Naohisa; Hirose, Shirou; Yokota, Noriko; Akanuma, Shin-Ichi; Tachikawa, Masanori; Hosoya, Ken-ichi

    2009-11-01

    The purpose of this study was to identify the transporter mediating l-arginine transport at the inner blood-retinal barrier (BRB). The apparent uptake clearance of [(3)H]L-arginine into the rat retina was found to be 118 microL/(min.g retina), supporting a carrier-mediated influx transport of L-arginine at the BRB. [(3)H]L-arginine uptake by a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2 cells), used as an in vitro model of the inner BRB, was primarily an Na(+)-independent and saturable process with Michaelis-Menten constants of 11.2 microM and 530 microM. This process was inhibited by rat cationic amino acid transporter (CAT) 1-specific small interfering RNA as well as substrates of CATs, L-arginine, L-lysine, and L-ornithine. The expression of cationic amino acid transporter (CAT) 1 mRNA was 25.9- and 796-fold greater than that of CAT3 in TR-iBRB2 and magnetically isolated rat retinal vascular endothelial cells, respectively. The expression of CAT1 protein was detected in TR-iBRB2 cells and immunostaining of CAT1 was observed along the rat retinal capillaries. In conclusion, CAT1 is localized in retinal capillary endothelial cells and at least in part mediates L-arginine transport at the inner BRB. This process seems to be closely involved in visual functions by supplying precursors of biologically important molecules like nitric oxide in the neural retina.

  1. Proliferative, anti-apoptotic and immune-enhancing effects of L-arginine in culture of skin fibroblasts.

    PubMed

    Kocic, H; Arsic, I; Stankovic, M; Tiodorovic, D; Ciric, V; Kocic, G

    2017-01-01

    Semi-essential amino acid L-arginine may be of fundamental importance in various intracellular and intercellular pathways related to skin repair and wound healing. Our current study was aimed to explore the effect of L-arginine on skin fibroblast (L929) signaling pathways involved in cell proliferation (Akt-pAkt kinase, Erk/pErk1/2 kinase, JNK/pJNK kinase and pStat-1), apoptosis (Bcl2 and Bax) and immune defense (NF-κB and CD26). Significant upregulation of Erk (p<0.011), pErk (p<0.017) and JNK (p<0.002) was documented, while the rise was not significant for pJNK kinase. The Akt/pAkt signaling pathway did not change significantly for the above-mentioned time and dose, while pStat-1 was significantly down regulated (p<0.011). The exposure of skin fibroblasts to L-arginine increased anti-apoptotic Bcl2/Bax stoichiometry ratio (p<0.05), obtained by calculation of their individual quantities. L-arginine was able to elicit NF-κB signaling through the increase of p65 active subunit level (p<0.004), while CD26 surface antigen level was not significantly changed. In conclusion, the exposure of skin fibroblasts to L-arginine may help in maintaining and stimulating skin fibroblast proliferative, anti-apoptotic and immune defense function. Therefore, the proposed L-arginine dose may be used for tissue regeneration application, which would be of importance in regenerative medicine, skin rejuvenation approaches and wound healing.

  2. l-arginine and l-NMMA for assessing cerebral endothelial dysfunction in ischaemic cerebrovascular disease: A systematic review.

    PubMed

    Karlsson, William K; Sørensen, Caspar G; Kruuse, Christina

    2017-01-01

    Endothelial dysfunction (ED), in particular cerebral ED, may be an essential biomarker for ischaemic cerebrovascular disease. However, there is no consensus on methods to best estimate cerebral ED. In this systematic review, we evaluate the use of l-arginine and N G -monomethyl-l-arginine (l-NMMA) for assessment of cerebral ED. A systematic search of PubMed, EMBASE and the Cochrane Library was done. We included studies investigating cerebrovascular response to l-arginine or l-NMMA in human subjects with vascular risk factors or ischaemic cerebrovascular disease. Seven studies (315 subjects) were eligible according to inclusion and exclusion criteria. Studies investigated the effect of age (n=2), type 2 diabetes mellitus (DM) (n=1), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (n=1), leukoaraiosis (n=1), and prior ischaemic stroke or transient ischaemic attack (TIA) (n=2) on cerebral ED. Most studies applied transcranial Doppler to quantify cerebral ED. Endothelium-dependent vasodilatation (EDV) induced by l-arginine was impaired in elderly and subjects with leukoaraiosis, but enhanced in CADASIL patients. Studies including subjects with prior ischaemic stroke or TIA reported both enhanced and impaired EDV to l-arginine. Responses to l-NMMA deviated between subjects with type 2 DM and the elderly. We found only few studies investigating cerebral endothelial responses to l-arginine and l-NMMA in subjects with vascular risk factors or ischaemic cerebrovascular disease. Inconsistencies in results were most likely due to variations in methods and included subject populations. In order to use cerebral ED as a prognostic marker, further studies are required to evaluate the association to cerebrovascular disease. © 2016 John Wiley & Sons Australia, Ltd.

  3. Targeting the superoxide/nitric oxide ratio by L-arginine and SOD mimic in diabetic rat skin.

    PubMed

    Jankovic, Aleksandra; Ferreri, Carla; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Stancic, Ana; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

    2016-11-01

    Setting the correct ratio of superoxide anion (O 2 •- ) and nitric oxide ( • NO) radicals seems to be crucial in restoring disrupted redox signaling in diabetic skin and improvement of • NO physiological action for prevention and treatment of skin injuries in diabetes. In this study we examined the effects of L-arginine and manganese(II)-pentaazamacrocyclic superoxide dismutase (SOD) mimic - M40403 in diabetic rat skin. Following induction of diabetes by alloxan (blood glucose level ≥12 mMol l  -1 ) non-diabetic and diabetic male Mill Hill hybrid hooded rats were divided into three subgroups: (i) control, and receiving: (ii) L-arginine, (iii) M40403. Treatment of diabetic animals started after diabetes induction and lasted for 7 days. Compared to control, lower cutaneous immuno-expression of endothelial NO synthase (eNOS), heme oxygenase 1 (HO1), manganese SOD (MnSOD) and glutathione peroxidase (GSH-Px), in parallel with increased NFE2-related factor 2 (Nrf2) and nitrotyrosine levels characterized diabetic skin. L-arginine and M40403 treatments normalized alloxan-induced increase in nitrotyrosine. This was accompanied by the improvement/restitution of eNOS and HO1 or MnSOD and GSH-Px protein expression levels in diabetic skin following L-arginine, i.e. SOD mimic treatments, respectively. The results indicate that L-arginine and M40403 stabilize redox balance in diabetic skin and suggest the underlying molecular mechanisms. Restitution of skin redox balance by L-arginine and M40403 may represent an effective strategy to ameliorate therapy of diabetic skin.

  4. L-Arginine Modulates Intestinal Inflammation in Rats Submitted to Mesenteric Ischemia-Reperfusion Injury.

    PubMed

    Taha, M O; de Oliveira, J V; Dias Borges, M; de Lucca Melo, F; Gualtieri, F G; E Silva Aidar, A L; Pacheco, R L; de Melo Alexandre E Silva, T; Klajner, R K; Iuamoto, L R; Munhoz Torres, L; Morais Mendes de Paula, B J; de Campos, K; Oliveira-Junior, I S; Fagundes, D J

    2016-03-01

    The goal of this study was to investigate whether exogenous offer of L-arginine (LARG) modulates the gene expression of intestinal dysfunction caused by ischemia and reperfusion. Eighteen Wistar-EPM1 male rats (250-300 g) were anesthetized and subjected to laparotomy. The superior mesenteric vessels were exposed, and the rats were randomized into 3 groups (n = 6): the control group (CG), with no superior mesenteric artery interruption; the ischemia/reperfusion group (IRG), with 60 minutes of ischemia and 120 minutes of reperfusion and saline injections; and the L-arginine group (IRG + LARG), with L-arginine injected in the femoral vein 5 minutes before ischemia, 5 minutes after reperfusion, and after 55 minutes of reperfusion. The total RNA was extracted and purified from samples of the small intestine. The concentration of each total RNA sample was determined by using spectrophotometry. The first-strand complementary DNA (cDNA) was synthesized in equal amounts of cDNA and the Master Mix SYBR Green qPCR Mastermix (SABiosciences, a Qiagen Company, Frederick, Md). Amounts of cDNA and Master Mix SYBR Green qPCR Mastermix were distributed to each well of the polymerase chain reaction microarray plate containing the predispensed gene-specific primer sets for Bax and Bcl2. Each sample was evaluated in triplicate, and the Student t test was applied to validate the homogeneity of each gene expression reaction (P < .05). The gene expression of Bax in IRG (+1.48) was significantly higher than in IRG-LARG (+9.69); the expression of Bcl2L1 in IRG (+1.01) was significantly higher than IRG-LARG (+22.89). The apoptotic cell pathway of 2 protagonists showed that LARG improves the gene expression of anti-apoptotic Bcl2l1 (Bcl2-like 1) more than the pro-apoptotic Bax (Bcl2-associated X protein). Copyright © 2016. Published by Elsevier Inc.

  5. The Association of Dietary l-Arginine Intake and Serum Nitric Oxide Metabolites in Adults: A Population-Based Study

    PubMed Central

    Mirmiran, Parvin; Bahadoran, Zahra; Ghasemi, Asghar; Azizi, Fereidoun

    2016-01-01

    This study was conducted to investigate whether regular dietary intake of l-arginine is associated with serum nitrate + nitrite (NOx). In this cross-sectional study, 2771 men and women, who had participated in the third examination of the Tehran Lipid and Glucose Study (2006–2008), were recruited. Demographics, anthropometrics and biochemical variables were evaluated. Dietary data were collected using a validated 168-food item semi-quantitative food frequency questionnaire and dietary intake of l-arginine was calculated. To determine any association between dietary l-arginine and serum NOx, linear regression models with adjustment for potential confounders were used. Mean age of participants (39.2% men) was 45.9 ± 15.9 years. After adjustment for all potential confounding variables, a significant positive association was observed between l-arginine intake and serum NOx concentrations in the fourth quartile of l-arginine (β = 6.63, 95% CI = 4.14, 9.12, p for trend = 0.001), an association stronger in women. Further analysis, stratified by age, body mass index and hypertension status categories, showed a greater association in middle-aged and older adults (β = 9.12, 95% CI = 3.99, 13.6 and β = 12.1, 95% CI = 6.48, 17.7, respectively). l-arginine intakes were also strongly associated with serum NOx levels in overweight and obese subjects in the upper quartile (β = 10.7, 95% CI = 5.43, 16.0 and β = 11.0, 95% CI = 4.29, 17.5); a greater association was also observed between l-arginine intakes and serum NOx in non-hypertensive (HTN) compared to HTN subjects (β = 2.65, 95% CI = 2.1–3.2 vs. β = 1.25, 95% CI = −1.64–4.15). Dietary l-arginine intakes were associated to serum NOx and this association may be affected by sex, age, body mass index, and hypertension status. PMID:27213443

  6. Ground based experiments on the growth and characterization of L-Arginine Phosphate (LAP) crystals

    NASA Technical Reports Server (NTRS)

    Rao, S. M.; Cao, C.; Batra, A. K.; Lal, R. B.; Mookherji, T. K.

    1991-01-01

    L-Arginine Phosphate (LAP) is a new nonlinear optical material with higher efficiency for harmonic generation compared to KDP. Crystals of LAP were grown in the laboratory from supersaturated solutions by temperature lowering technique. Investigations revealed the presence of large dislocation densities inside the crystals which are observed to produce refractive index changes causing damage at high laser powers. This is a result of the convection during crystal growth from supersaturated solutions. It is proposed to grow these crystals in a diffusion controlled growth condition under microgravity environment and compare the crystals grown in space with those grown on ground. Physical properties of the solutions needed for modelling of crystal growth are also presented.

  7. [L-arginine metabolism enzyme activities in rat liver subcellular fractions under condition of protein deprivation].

    PubMed

    Kopyl'chuk, G P; Buchkovskaia, I M

    2014-01-01

    The features of arginase and NO-synthase pathways of arginine's metabolism have been studied in rat liver subcellular fractions under condition of protein deprivation. During the experimental period (28 days) albino male rats were kept on semi synthetic casein diet AIN-93. The protein deprivation conditions were designed as total absence of protein in the diet and consumption of the diet partially deprived with 1/2 of the casein amount compared to in the regular diet. Daily diet consumption was regulated according to the pair feeding approach. It has been shown that the changes of enzyme activities, involved in L-arginine metabolism, were characterized by 1.4-1.7 fold decrease in arginase activity, accompanied with unchanged NO-synthase activity in cytosol. In mitochondrial fraction the unchanged arginase activity was accompanied by 3-5 fold increase of NO-synthase activity. At the terminal stages of the experiment the monodirectional dynamics in the studied activities have been observed in the mitochondrial and cytosolfractions in both experimental groups. In the studied subcellular fractions arginase activity decreased (2.4-2.7 fold with no protein in the diet and 1.5 fold with partly supplied protein) and was accompanied by NO-synthase activity increase by 3.8 fold in cytosole fraction, by 7.2 fold in mitochondrial fraction in the group with no protein in the diet and by 2.2 and 3.5 fold in the group partialy supplied with protein respectively. The observed tendency is presumably caused by the switch of L-arginine metabolism from arginase into oxidizing NO-synthase parthway.

  8. Morphine hyposensitivity in streptozotocin-diabetic rats: Reversal by dietary l-arginine treatment.

    PubMed

    Lotfipour, Shahrdad; Smith, Maree T

    2018-01-01

    Painful diabetic neuropathy (PDN) is a long-term complication of diabetes. Defining symptoms include mechanical allodynia (pain due to light pressure or touch) and morphine hyposensitivity. In our previous work using the streptozotocin (STZ)-diabetic rat model of PDN, morphine hyposensitivity developed in a temporal manner with efficacy abolished at 3 months post-STZ and maintained for 6 months post-STZ. As this time course mimicked that for the temporal development of hyposensitivity to the pain-relieving effects of the furoxan nitric oxide (NO) donor, PRG150 (3-methylfuroxan-4-carbaldehyde) in STZ-diabetic rats, we hypothesized that progressive depletion of endogenous NO bioactivity may underpin the temporal loss of morphine sensitivity in STZ-diabetic rats. Furthermore, we hypothesized that replenishment of NO bioactivity may restore morphine sensitivity in these animals. Diabetes was induced in male Dark Agouti rats by intravenous injection of STZ (85 mg/kg). Diabetes was confirmed on day 7 if blood glucose concentrations were ≥15 mmol/L. Mechanical allodynia was fully developed in the bilateral hindpaws by 3 weeks of STZ-diabetes in rats and this was maintained for the study duration. Morphine hyposensitivity developed in a temporal manner with efficacy abolished by 3 months post-STZ. Administration of dietary l-arginine (NO precursor) at 1 g/d to STZ-diabetic rats according to a 15-week prevention protocol initiated at 9 weeks post-STZ prevented abolition of morphine efficacy. When given as an 8-week intervention protocol in rats where morphine efficacy was abolished, dietary l-arginine at 1 g/d progressively rescued morphine efficacy and potency. Our findings implicate NO depletion in the development of morphine hyposensitivity in STZ-diabetic rats. © 2017 John Wiley & Sons Australia, Ltd.

  9. Enhanced nonlinear optical properties of L-arginine stabilized gold nanoparticles embedded in PVP polymer

    NASA Astrophysics Data System (ADS)

    Sunatkari, A. L.; Talwatkar, S. S.; Tamgadge, Y. S.; Muley, G. G.

    2018-05-01

    Highly stable colloidal gold nanoparticles (GNPs) stabilised in l-arginine were synthesized and embedded in polyvinyl pyrrolidone (PVP) polymer matrix to fabricate thin films by spin coating method. Nonlinear optical response of GNP-PVP nanocomposite were investigated using single beam Z-scan technique using He-Ne laser beam in CW regime operated at 632.8 nm as an excitation source. The sign of nonlinear refractive index was found negative, which is of self-defocusing nature. The nonlinear optical parameters estimated for GNP-PVP nanocomposite and found values as large as n2≈(1.7 -3.1 ) ×10-4c m2W-1, β ≈(2.40 -4.69 ) ×10-5c m W-1 and χef f (3 )≈(2.30 -4.34 ) ×10-4e s u . The nonlinear refractive index, absorption coefficient and third order nonlinear susceptibility have found decreasing with the increase in the concentration of l-arginine. Localized surface plasmon resonance (LSPR) peaks show the blue shift. The average size of the GNPs is found reducing from 11 nm to 7.5 nm with the increase in the stabilizer concentration, as analysed by transmission electron microscopy. The XRD study reveals face-centred cubic (fcc) structure of GNPs. The huge nonlinearity is attributed to the thermo-optic phenomenon. The huge enhancement in third order nonlinear susceptibility and nonlinear refractive index indicates that this optical material possess a high potential for various optoelectronic devices applications.

  10. Orally administered L-arginine and glycine are highly effective against acid reflux esophagitis in rats

    PubMed Central

    Nagahama, Kenji; Nishio, Hikaru; Yamato, Masanori; Takeuchi, Koji

    2012-01-01

    Summary Background Reflux esophagitis is caused mainly by excessive exposure of the mucosa to gastric contents. In the present study, we examined the effect of several amino acids on acid reflux esophagitis in rats. Material/Methods After 18 h of fasting, acid reflux esophagitis was induced by ligating both the pylorus and the transitional region between the forestomach and the corpus under ether anesthesia, and the animals were killed 4 h later. The severity of esophagitis was reduced by the oral administration of omeprazole, a proton pump inhibitor, or pepstatin, a specific pepsin inhibitor. Results The development of esophageal lesions was dose-dependently prevented by L-arginine and glycine, given intragastrically (i.g.) after the ligation, with complete inhibition obtained at 250 mg/kg and 750 mg/kg, respectively, and these effects were not influenced by the prior s.c. administration of indomethacin or L-NAME. By contrast, both L-alanine and L-glutamine given i.g. after the ligation aggravated these lesions in a dose-dependent manner. These amino acids had no effect on acid secretion but increased the pH of the gastric contents to 1.8~2.3 due to their buffering action. Conclusions The results confirmed an essential role for acid and pepsin in the pathogenesis of acid reflux esophagitis in the rat model and further suggested that various amino acids affect the severity of esophagitis in different ways, due to yet unidentified mechanisms; L-alanine and L-glutamine exert a deleterious effect on the esophagitis, while L-arginine and glycine are highly protective, independent of endogenous prostaglandins and nitric oxide. PMID:22207112

  11. l-Arginine Uptake by Cationic Amino Acid Transporter Promotes Intra-Macrophage Survival of Leishmania donovani by Enhancing Arginase-Mediated Polyamine Synthesis

    PubMed Central

    Mandal, Abhishek; Das, Sushmita; Kumar, Ajay; Roy, Saptarshi; Verma, Sudha; Ghosh, Ayan Kumar; Singh, Ruby; Abhishek, Kumar; Saini, Savita; Sardar, Abul Hasan; Purkait, Bidyut; Kumar, Ashish; Mandal, Chitra; Das, Pradeep

    2017-01-01

    The survival of intracellular protozoan parasite, Leishmania donovani, the causative agent of Indian visceral leishmaniasis (VL), depends on the activation status of macrophages. l-Arginine, a semi-essential amino acid plays a crucial regulatory role for activation of macrophages. However, the role of l-arginine transport in VL still remains elusive. In this study, we demonstrated that intra-macrophage survival of L. donovani depends on the availability of extracellular l-arginine. Infection of THP-1-derived macrophage/human monocyte-derived macrophage (hMDM) with Leishmania, resulted in upregulation of l-arginine transport. While investigating the involvement of the transporters, we observed that Leishmania survival was greatly impaired when the transporters were blocked either using inhibitor or siRNA-mediated downregulation. CAT-2 was found to be the main isoform associated with l-arginine transport in L. donovani-infected macrophages. l-arginine availability and its transport regulated the host arginase in Leishmania infection. Arginase and inducible nitric oxide synthase (iNOS) expression were reciprocally regulated when assayed using specific inhibitors and siRNA-mediated downregulation. Interestingly, induction of iNOS expression and nitric oxide production were observed in case of inhibition of arginase in infected macrophages. Furthermore, inhibition of l-arginine transport as well as arginase resulted in decreased polyamine production, limiting parasite survival inside macrophages. l-arginine availability and transport regulated Th1/Th2 cytokine levels in case of Leishmania infection. Upregulation of l-arginine transport, induction of host arginase, and enhanced polyamine production were correlated with increased level of IL-10 and decreased level of IL-12 and TNF-α in L. donovani-infected macrophages. Our findings provide clear evidence for targeting the metabolism of l-arginine and l-arginine-metabolizing enzymes as an important therapeutic and

  12. The effects of L-arginine on cerebral hemodynamics after controlled cortical impact injury in the mouse.

    PubMed

    Liu, Hao; Goodman, J Clay; Robertson, Claudia S

    2002-03-01

    Traumatic brain injury (TBI) induces vascular changes that may influence neurological outcome by causing the brain to be more susceptible to secondary ischemic insults. In rat models of TBI, L-arginine administration has been shown to restore cerebral blood flow and improve neurological outcome. The purpose of this study was to determine if hypoperfusion occurs in a mouse model of TBI and if L-arginine administration has the same beneficial effects after injury in the mouse. C57BL6 mice were anesthetized with isoflurane, intubated and mechanically ventilated, and underwent a 3-m/sec, 1.5-mm deformation cortical impact injury. Five minutes after injury, L-arginine, 300 mg/kg, or saline were administered. Arterial blood pressure, intracranial pressure, and laser Doppler flow at the impact site were monitored for 3 h after the injury. The cerebral hemodynamic effects of the TBI induced by cortical impact injury were similar to that previously observed in rats. Intracranial hypertension, with ICP peaking at 46+/-2 mm Hg, and systemic hypotension both contributed to a reduction in CPP. In addition, LDF decreased significantly at the impact site. L-Arginine administration restored LDF to near baseline levels without increasing ICP. These studies demonstrate that cerebral hemodynamics can be measured in mouse models of TBI. The changes in cerebral hemodynamics are relatively simlar to those see in the rat model of cortical impact injury and suggest an important role for nitric oxide metabolism in the maintenance of cerebral blood flow following TBI.

  13. Plasma asymmetric dimethylarginine, L-arginine and Left Ventricular Structure and Function in a Community-based Sample

    PubMed Central

    Lieb, Wolfgang; Benndorf, Ralf A.; Benjamin, Emelia J.; Sullivan, Lisa M.; Maas, Renke; Xanthakis, Vanessa; Schwedhelm, Edzard; Aragam, Jayashri; Schulze, Friedrich; Böger, Rainer H.; Vasan, Ramachandran S.

    2009-01-01

    Objective Increasing evidence indicates that cardiac structure and function are modulated by the nitric oxide (NO) system. Elevated plasma concentrations of asymmetric dimethylarginine (ADMA; a competitive inhibitor of NO synthase) have been reported in patients with end-stage renal disease. It is unclear if circulating ADMA and L-arginine levels are related to cardiac structure and function in the general population. Methods We related plasma ADMA and L-Arginine (the amino acid precursor of NO) to echocardiographic left ventricular (LV) mass, left atrial (LA) size and fractional shortening (FS) using multivariable linear regression analyses in 1,919 Framingham Offspring Study participants (mean age 57 years, 58 % women). Results Overall, neither ADMA or L-arginine, nor their ratio was associated with LV mass, LA size and FS in multivariable models (p>0.10 for all). However, we observed effect modification by obesity of the relations of ADMA and LA size (p for interaction p=0.04): ADMA was positively related to LA size in obese individuals (adjusted-p=0.0004 for trend across ADMA quartiles) but not in non-obese people. Conclusion In our large community-based sample, plasma ADMA and L-arginine concentrations were not related to cardiac structure or function. The observation of positive relations of LA size and ADMA in obese individuals warrants confirmation. PMID:18829028

  14. Preferential interactions of trehalose, L-arginine.HCl and sodium chloride with therapeutically relevant IgG1 monoclonal antibodies.

    PubMed

    Sudrik, Chaitanya; Cloutier, Theresa; Pham, Phuong; Samra, Hardeep S; Trout, Bernhardt L

    2017-10-01

    Preferential interactions of weakly interacting formulation excipients govern their effect on the equilibrium and kinetics of several reactions of protein molecules in solution. Using vapor pressure osmometry, we characterized the preferential interactions of commonly used excipients trehalose, L-arginine.HCl and NaCl with three therapeutically-relevant, IgG1 monoclonal antibodies that have similar size and shape, but differ in their surface hydrophobicity and net charge. We further characterized the effect of these excipients on the reversible self-association, aggregation and viscosity behavior of these antibody molecules. We report that trehalose, L-arginine.HCl and NaCl are all excluded from the surface of the three IgG1 monoclonal antibodies, and that the exclusion behavior is linearly related to the excipient molality in the case of trehalose and NaCl, whereas a non-linear behavior is observed for L-arginine.HCl. Interestingly, we find that the magnitude of trehalose exclusion depends upon the nature of the protein surface. Such behavior is not observed in case of NaCl and L-arginine.HCl as they are excluded to the same extent from the surface of all three antibody molecules tested in this study. Analysis of data presented in this study provides further insight into the mechanisms governing excipient-mediated stabilization of mAb formulations.

  15. Plasma asymmetric dimethylarginine, L-arginine and left ventricular structure and function in a community-based sample.

    PubMed

    Lieb, Wolfgang; Benndorf, Ralf A; Benjamin, Emelia J; Sullivan, Lisa M; Maas, Renke; Xanthakis, Vanessa; Schwedhelm, Edzard; Aragam, Jayashri; Schulze, Friedrich; Böger, Rainer H; Vasan, Ramachandran S

    2009-05-01

    Increasing evidence indicates that cardiac structure and function are modulated by the nitric oxide (NO) system. Elevated plasma concentrations of asymmetric dimethylarginine (ADMA; a competitive inhibitor of NO synthase) have been reported in patients with end-stage renal disease. It is unclear if circulating ADMA and L-arginine levels are related to cardiac structure and function in the general population. We related plasma ADMA and L-arginine (the amino acid precursor of NO) to echocardiographic left ventricular (LV) mass, left atrial (LA) size and fractional shortening (FS) using multivariable linear regression analyses in 1919 Framingham Offspring Study participants (mean age 57 years, 58% women). Overall, neither ADMA or L-arginine, nor their ratio was associated with LV mass, LA size and FS in multivariable models (p>0.10 for all). However, we observed effect modification by obesity of the relations of ADMA and LA size (p for interaction p=0.04): ADMA was positively related to LA size in obese individuals (adjusted-p=0.0004 for trend across ADMA quartiles) but not in non-obese people. In our large community-based sample, plasma ADMA and l-arginine concentrations were not related to cardiac structure or function. The observation of positive relations of LA size and ADMA in obese individuals warrants confirmation.

  16. Effects of adenosine monophosphate used in combination with L-arginine on female rabbit corpus cavernosum tissue.

    PubMed

    Stücker, Olivier; Pons, Catherine; Neuzillet, Yann; Laemmel, Elisabeth; Lebret, Thierry

    2014-04-01

    Sexual dysfunction is significantly more prevalent in women than in men. However, to date, no satisfactory oral treatment is yet available. The aim of this study was to study the effects of adenosine monophosphate (AMP) alone or its combination with L-Arginine on the relaxation of the female rabbit corpus cavernosum. Cylinder strips from the corporal body of the excised clitoris from female New Zealand White rabbits were incubated in Krebs solution. Phenylephrine (PE) precontraction was achieved, then the drugs AMP and L-Arginine were administered either independently or in sequential combinations to the strips under precontracted conditions. Contraction percentages were compared. When precontraction was induced by PE 8 μM or 20 μM, AMP was shown to induce relaxation up to 25% in a dose-dependent manner. The relaxation induced by L-Arginine reached 15.6% at 5.10(-4) M vs. 16.5% at AMP 5.10(-4) M under the same experimental conditions. Nitric oxide (NO) synthase inhibitor N-nitro-L-arginine strongly inhibited the relaxing effect provoked by AMP, suggesting that the action mechanism of this nucleotide is related to the NO pathway. The combination of L-Arginine at 5.10(-4) M with AMP at different doses ranging from 5.10(-4) M to 10(-3) M significantly amplified the relaxing response up to 40.7% and 58%, respectively. Our results demonstrate that AMP induces a relaxing effect on the female rabbit corpora. They also show that L-Arginine and AMP can potentiate each other and that a synergistic effect can be obtained by their combined use. Because only slight differences exist between both sexes in response to NO donors and/or nucleotide purines or in their use together, it is very likely that close biochemical mechanisms, although not to the same degree and not quite similar, are involved in the engorgement of the penis and the clitoris of New Zealand White rabbits. Stücker O, Pons C, Neuzillet Y, Laemmel E, and Lebret T. Original research-sexual medicine: Effects of

  17. Midkine is overexpressed in acute pancreatitis and promotes the pancreatic recovery in L-arginine-induced acute pancreatitis in mice.

    PubMed

    Cheng, Li; Qiao, Zhenguo; Xu, Chunfang; Shen, Jiaqing

    2017-06-01

    Midkine (MK) is involved in the pathogenesis of numerous malignancies, but the expression and effect of MK in acute pancreatitis (AP) have not been well studied and documented. In this study, the expression of MK was assayed in mice with L-arginine-induced AP. A recombinant human MK (rhMK) was introduced in this study to test the effect of MK on the L-arginine-induced AP. Serum amylase and lipase were assayed. Pancreas tissue samples were also collected for the evaluation of histological injury. Western blot and immunochemical staining of α-amylase and proliferating cell nuclear antigen were applied for the study of acinar regeneration in the pancreas. The elevation of MK expression was found in mice with AP induced by L-arginine. After rhMK administration, rhMK did not affect the severity of acute pancreatic injury in acute phase in L-arginine-induced pancreatitis in mice, in accordance with changes of serum amylase and lipase and the histological evaluation. But during the recovery phase, the area of remaining acinar cells was increased and the fibrosis was reduced in rhMK-treated mice. Furthermore, the expression of proliferating cell nuclear antigen and α-amylase was also upregulated after rhMK treatment. Midkine is over-expressed during AP in the animal model. Recombinant MK could promote the recovery of L-arginine-induced pancreatitis in mice. Therefore, MK may be involved in the regeneration of acinar cells in AP, and rhMK may be a possible therapeutic intervention for the repairment of AP. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  18. Exogenous L-Arginine Attenuates the Effects of Angiotensin II on Renal Hemodynamics and the Pressure Natriuresis-Diuresis Relationship

    PubMed Central

    Das, Satarupa; Mattson, David L.

    2014-01-01

    SUMMARY Administration of exogenous L-Arginine (L-Arg) attenuates Angiotensin II (AngII)-mediated hypertension and kidney disease in rats. The present study assessed renal hemodynamics and pressure-diuresis-natriuresis in anesthetized rats infused with vehicle, AngII (20 ng/kg/min, iv) or AngII + L-Arg (300 µg/kg/min, iv). Increasing renal perfusion pressure (RPP) from approximately 100 to 140 mmHg resulted in a 9–10 fold increase in urine flow and sodium excretion rate in control animals. In comparison, AngII infusion significantly reduced renal blood flow (RBF) and glomerular filtration rate (GFR) by 40–42% and blunted the pressure-dependent increase in urine flow and sodium excretion rate by 54–58% at elevated RPP. Supplementation of L-Arg reversed the vasoconstrictor effects of AngII and restored pressure-dependent diuresis to levels not significantly different from control rats. Experiments in isolated aortic rings were performed to assess L-Arg effects on the vasculature. Dose-dependent contraction to AngII (10−10M to 10−7M) was observed with a maximal force equal to 27±3% of the response to 10−5M phenylephrine. Contraction to 10−7M AngII was blunted by 75±3% with 10−4M L-Arg. The influence of L-Arg to blunt AngII mediated contraction was eliminated by endothelial denudation or incubation with nitric oxide synthase inhibitors. Moreover, the addition of 10−3M cationic or neutral amino acids, which compete with L-Arg for cellular uptake, blocked the effect of L-Arg. Anionic amino acids did not influence the effects of L-Arg on AngII-mediated contraction. These studies indicate that L-Arg blunts AngII-mediated vascular contraction by an endothelial- and NOS-dependent mechanism involving cellular uptake of L-Arg. PMID:24472006

  19. L-arginine reduces liver and biliary tract damage after liver transplantation from non-heart-beating donor pigs.

    PubMed

    Valero, R; García-Valdecasas, J C; Net, M; Beltran, J; Ordi, J; González, F X; López-Boado, M A; Almenara, R; Taurá, P; Elena, M; Capdevila, L; Manyalich, M; Visa, J

    2000-09-15

    To evaluate whether L-arginine reduces liver and biliary tract damage after transplantation from non heart-beating donor pigs. Twenty-five animals received an allograft from non-heart-beating donors. After 40 min of cardiac arrest, normothermic recirculation was run for 30 min. The animals were randomly treated with L-arginine (400 mg x kg(-1) during normothermic recirculation) or saline (control group). Then, the animals were cooled and their livers were transplanted after 6 hr of cold ischemia. The animals were killed on the 5th day, liver damage was assessed on wedged liver biopsies by a semiquantitative analysis and by morphometric analysis of the necrotic areas, and biliary tract damage by histological examination of the explanted liver. Seventeen animals survived the study period. The histological parameters assessed (sinusoidal congestion and dilatation, sinusoidal infiltration by polymorphonuclear cells and lymphocytes, endothelitis, dissociation of liver cell plates, and centrilobular necrosis) were significantly worse in the control group. The necrotic area affected 15.9 +/- 14.5% of the liver biopsies in the control group and 3.7 +/- 3.1% in the L-arginine group (P<0.05). Six of eight animal in the control group and only one of eight survivors in the L-arginine group developed ischemic cholangitis (P<0.01). L-Arginine administration was associated with higher portal blood flow (676.9 +/- 149.46 vs. 475.2 +/- 205.6 ml x min x m(-2); P<0.05), higher hepatic hialuronic acid extraction at normothermic recirculation (38.8 +/- 53.7% vs. -4.2 +/- 18.2%; P<0.05) and after reperfusion (28.6 +/- 55.5% vs. -10.9 +/- 15.5%; P<0.05) and lower levels of alpha-glutation-S-transferase at reperfusion (1325 +/- 1098% respect to baseline vs. 6488 +/- 5612%; P<0.02). L-Arginine administration during liver procurement from non heart beating donors prevents liver and biliary tract damage.

  20. Growth habit and surface morphology of L-arginine phosphate monohydrate single crystals

    NASA Astrophysics Data System (ADS)

    Sangwal, K.; Veintemillas-Verdaguer, S.; Torrent-Burgués, J.

    1995-10-01

    The results of a study of the growth habit and the surface topography of L-arginine phosphate monohydrate (LAP) single crystals as a function of supersaturation are described and discussed. Apart from a change in the growth habit with supersaturation, it was observed that most of the as-grown faces of LAP exhibit isolated growth hillocks and macrohillocks and parallel bunched layers and that the formation of bunched layers is pronounced on faces showing macrohillocks. Observations of bunching of growth layers emitted by macrohillocks on the {100} faces revealed that, for the onset of bunching close to a macrospiral, there is a characteristic threshold distance whose value depends on the interstep distance and supersaturation, but is independent of step height. The theoretical habit of LAP deduced from PBC analysis showed that all faces exhibiting growth hillocks and macrohillocks are F faces. Analysis of the results on bunch formation revealed that growth of LAP takes place by the direct integration of growth entities at the growth steps, that the bunching is facilitated by an increasing value of the activation energy for their integration, and that the observed dependencies of threshold distance on interstep distance, supersaturation and step height are qualitatively in agreement with van der Eerden and Müller-Krumbhaar's theory of bunch formation.

  1. Formation and enzymatic degradation of poly-l-arginine/fucoidan multilayer films.

    PubMed

    Webber, Jessie L; Benbow, Natalie L; Krasowska, Marta; Beattie, David A

    2017-11-01

    A polyelectrolyte multilayer (PEM) system based on biopolymers has been constructed and studied in its formation and enzymatic breakdown. The multilayer is composed of fucoidan (a proven antimicrobial/anti-inflammatory seaweed-based polysaccharide) and poly-l-arginine (a polypeptide that can be readily degraded with trypsin to yield arginine, a known NO donor), thus making the multilayer a potential dual action surface treatment for wound dressings. Studies on the formation of the multilayer revealed that the film built-up in the expected stepwise manner with consistent reversal of the zeta potential upon the adsorption of each subsequent polyion. The completed film (8 bilayers) was seen to have low hydration (30% water), as determined by H 2 O/D 2 O solvent replacement studies using the quartz crystal microbalance, with an adsorbed mass (without hydration water) of approx. 4.8μgcm -2 , as determined by quantitative attenuated total reflectance Fourier transform infrared (ATR FTIR) spectroscopy. The enzymatic breakdown of the film in response to exposure to trypsin was also investigated, and the film was seen to release both polymers over time, with a projected complete film removal period of approximately 24h. Critically, this information was determined using ATR FTIR spectroscopy experiments, which allowed unambiguous deconvolution of the removal rates of the two polyions, which is information that cannot be obtained from other methodologies used to study enzymatic breakdown of surface films. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Effect of pravastatin on responsiveness to N-monomethyl-L-arginine in patients with hypercholesterolaemia.

    PubMed

    Bayerle-Eder, Michaela; Fuchsjäger-Mayrl, Gabriele; Sieder, Anna; Polska, Elzbieta; Roden, Michael; Stulnig, Thomas; Bischof, Martin G; Waldhäusl, Werner; Schmetterer, Leopold; Wolzt, Michael

    2002-01-01

    Improvement of endothelial function in hypercholesterolaemia is attributed to lipid lowering and to pleiotropic effects of statin therapy. We investigated whether responsiveness to inhibition of constitutive NO formation with N-monomethyl-L-arginine (L-NMMA) is improved after 7 and 28 days of pravastatin. Twelve female and four male subjects with mild or moderate primary hypercholesterolaemia were randomized to pravastatin (20 mg per oral (p.o.) n=8) or placebo (n=8) in a double blind parallel group design. Vascular responsiveness was studied by intravenous bolus infusions of L-NMMA (cumulative doses of 3 and 6 mg/kg). Mean arterial blood pressure (MAP) and pulse rate (PR) were measured noninvasively, pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation amplitudes (FPA) and renal plasma flow (RPF) was measured by the PAH clearance method. Pravastatin lowered plasma cholesterol levels by 16 and 24% after 7 and 28 days of treatment, respectively (P<0.01). L-NMMA caused comparable changes in MAP, PR and RPF between groups. L-NMMA reduced FPA to a similar extent in both groups before and after 7 days of treatment, but the response to L-NMMA was significantly enhanced after 28 days of pravastatin (21%; P<0.001 vs baseline) and greater than after placebo (15%; P<0.01 vs pravastatin). Pravastatin enhances responsiveness to L-NMMA in the ocular microvasculature. Improved responsiveness is associated with changes in total cholesterol levels.

  3. Effects of L-arginine on anatomical and electrophysiological deterioration of the eye in a rodent model of nonarteritic ischemic optic neuropathy.

    PubMed

    Chuman, Hideki; Maekubo, Tomoyuki; Osako, Takako; Ishiai, Michitaka; Kawano, Naoko; Nao-I, Nobuhisa

    2013-07-01

    The aims of this study were to clarify the effectiveness of L-arginine (1) for reducing the severity of anatomical changes in the eye and improving visual function in the acute stage of a rodent model of nonarteritic ischemic optic neuropathy (rNAION) and (2) in preventing those changes in anatomy and visual function. For the first aim, L-arginine was intravenously injected into rats 3 h after rNAION induction; for the second aim, rNAION was induced after the oral administration of L-arginine for 7 days. The inner retinal thickness was determined over time by optical coherence tomography, and the amplitude of the scotopic threshold response (STR) and the number of surviving retinal ganglion cells (RGCs) were measured. These data were compared with the baseline data from the control group. Both intravenous infusion of L-arginine after rNAION induction and oral pretreatment with L-arginine significantly decreased optic disc edema in the acute stage and thinning of the inner retina, reduced the decrease in STR amplitude, and reduced the decrease in the number of RGCs during rNAION. Based on these results, we conclude that L-arginine treatment is effective for reducing anatomical changes in the eye and improving visual function in the acute stage of rNAION and that pretreatment with L-arginine is an effective therapy to reduce the severity of the condition during recurrence in the other eye.

  4. Dietary L-Arginine Intakes and the Risk of Metabolic Syndrome: A 6-Year Follow-Up in Tehran Lipid and Glucose Study.

    PubMed

    Mirmiran, Parvin; Moghadam, Sajjad Khalili; Bahadoran, Zahra; Ghasemi, Asghar; Azizi, Fereidoun

    2017-12-01

    This study was conducted to investigate whether regular dietary intake of L-arginine could affect the occurrence of metabolic syndrome (MetS). Eligible adult men and women (n=1,237), who participated in the Tehran Lipid and Glucose Study, were followed for a median of 6.3 years. Dietary intakes of L-arginine and serum nitrate and nitrite (NOx) concentration were assessed at baseline (2006~2008), and demographics, anthropometrics, and biochemical variables were evaluated at baseline and follow-up examinations. The occurrence of MetS was assessed in relation to total L-arginine, intakes of L-arginine from animal and plant sources, with adjustment of potential confounding variables. Participants who had higher intake of L-arginine also had higher serum NOx at baseline (35.0 vs. 30.5 μmol/L, P <0.05). After 6 years of follow-up, higher intakes of L-arginine from animal sources were accompanied with increased risk of MetS [odd ratios (OR)=1.49, 95% confidence interval (95% CI)=1.02~2.18]. Compared to the lowest, the highest intakes of L-arginine from plant sources were related to significantly reduced risk of MetS (OR=0.58, 95% CI=0.32~0.99). In conclusion, our findings suggest a potentially protective effect of plant derived L-arginine intakes against development of MetS and its phenotypes; moreover, higher intakes of L-arginine from animal sources could be a dietary risk factor for development of metabolic disorders.

  5. L-arginine levels are diminished in adult acute vaso-occlusive sickle cell crisis in the emergency department.

    PubMed

    Lopez, Bernard L; Kreshak, Allyson A; Morris, Claudia R; Davis-Moon, Linda; Ballas, Samir K; Ma, Xin-Liang

    2003-02-01

    Paediatric studies have demonstrated that l-arginine (l-arg), the precursor to nitric oxide, is diminished in vaso-occlusive crisis (VOC). This study aimed to determine whether l-arginine levels are altered in adult VOC in the emergency department. Plasma l-arg and nitric oxide metabolite (NOx) levels were obtained in adult VOC patients presenting to the emergency department. Fifty patients had significantly low plasma l-arg (29.78 micromol/l +/- 11.21, P < 0.05 vs steady-state control = 41.16 micromol/l +/- 5.04) and significantly low plasma NOx (12.33 micromol/l +/- 10.28, P < 0.05 vs steady-state control = 25.2 +/- 2.6 micro mol/l). Neither l-arg nor NOx levels could predict VOC clinical course.

  6. [Role of the L-arginine-NO system in the prevention and treatment of cardiovascular diseases in pregnant women].

    PubMed

    Vladymyrov, O A; Tofan, N I

    2003-01-01

    Investigations on using of index possibilities of L-arginin/NO system in evaluation of sanatorium-resort treatment effectiveness of pregnant with cardiovascular disorders were conducted. It was analyzed the dynamics of twenty four hour cycle rhythm of L-arginin and total nitrites and nitrates constance in saliva of 58 pregnant, 20 of which were suffering from metabolic cardiomyopathy, 23-from neurocirculatory dystonia and 15 were healthy pregnant. As the result of examination there were found out considerable changes of parameter values of biological rhythms: duration of rhythm, average twenty four hour cycle range of activity, amount of difference between max index per twenty hour cycle and average index per twenty hour cycle, period of max and min activity. Analysis of tendencies of twenty four hour cycles rhythms concerning dynamics of sanatorium-resort treatment will give possibility to define characteristic features of recovering values of this parameter.

  7. Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine.

    PubMed

    Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

    2015-01-01

    BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)-rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157 μg+L-NAME; BPC 157 μg+L-arginine, BPC 157 μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms.

  8. Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine

    PubMed Central

    Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

    2015-01-01

    Background BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Methods Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. Results After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)–rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157μg+L-NAME; BPC 157μg+L-arginine, BPC 157μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. Conclusions L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms. PMID:25897838

  9. Antioxidant Activity of Syringic Acid Prevents Oxidative Stress in l-arginine-Induced Acute Pancreatitis: An Experimental Study on Rats.

    PubMed

    Cikman, Oztekin; Soylemez, Omer; Ozkan, Omer Faruk; Kiraz, Hasan Ali; Sayar, Ilyas; Ademoglu, Serkan; Taysi, Seyithan; Karaayvaz, Muammer

    2015-05-01

    The aim of this study was to investigate the possible protective role of antioxidant treatment with syringic acid (SA) on l-arginine-induced acute pancreatitis (AP) using biochemical and histopathologic approaches. A total of 30 rats were divided into 3 groups. The control group received normal saline intraperitoneally. The AP group was induced by 3.2 g/kg body weight l-arginine intraperitoneally, administered twice with an interval of 1 hour between administrations. The AP plus SA group, after having AP induced by 3.2 g/kg body weight l-arginine, was given SA (50 mg kg(-1)) in 2 parts within 24 hours. The rats were killed, and pancreatic tissue was removed and used in biochemical and histopathologic examinations. Compared with the control group, the mean pancreatic tissue total oxidant status level, oxidative stress index, and lipid hydroperoxide levels were significantly increased in the AP group, being 30.97 ± 7.13 (P < 0.05), 1.76 ± 0.34 (P < 0.0001), and 19.18 ± 4.91 (P < 0.01), respectively. However, mean total antioxidant status and sulfhydryl group levels were significantly decreased in the AP group compared with the control group, being 1.765 ± 0.21 (P < 0.0001) and 0.21 ± 0.04 (P < 0.0001), respectively. SA reduces oxidative stress markers and has antioxidant effects. It also augments antioxidant capacity in l-arginine-induced acute toxicity of pancreas in rats.

  10. Heat Shock Proteins, L-Arginine, and Asymmetric Dimethylarginine Levels in Patients With Obstructive Sleep Apnea Syndrome.

    PubMed

    İn, Erdal; Özdemir, Cengiz; Kaman, Dilara; Sökücü, Sinem Nedime

    2015-11-01

    Vascular endothelial inflammation and enhanced oxidative stress are important factors in the pathogenesis of obstructive sleep apnea syndrome (OSAS). The aim of this study was to determine the levels of heat shock protein (HSP) 27, HSP70, HSP90, L-arginine, and asymmetric dimethylarginine (ADMA) in patients with OSAS and determine their relationship with cardiovascular (CV) risk factors. Forty patients with OSAS, comprising 26 with and 14 without traditional CV risk factors (obesity, hypercholesterolemia, diabetes, hypertension, and smoking), and 20 control subjects without OSAS were included. All patients underwent a full polysomnographic evaluation, and blood samples were obtained in the morning after the night the diagnostic study was performed. No significant differences were found in serum HSP27 and HSP70 levels between the groups. HSP90 and ADMA levels increased significantly, whereas L-arginine levels decreased significantly in patients with OSAS, both with and without CV risk factors, compared with controls, but were not different among the subgroups. In all patients with OSAS, serum HSP70 levels were positively correlated with a percent time with saturation<90% (r=.349, P=.027). Serum L-arginine levels were negatively correlated with desaturation number (r=-.360, P=.022) and apnea-hypopnea index (r=-.354, P=.025) and positively correlated with mean oxygen saturation (r=.328, P=.039). Serum levels of HSP90 and ADMA increased, whereas those of L-arginine decreased in patients with OSAS regardless of CV risk factors. These findings indicate the presence of oxidative stress and endothelial dysfunction in patients with OSAS. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

  11. Antioxidative and myocardial protective effects of L-arginine in oxygen radical-induced injury of isolated perfused rat hearts.

    PubMed

    Suessenbacher, Astrid; Lass, Achim; Mayer, Bernd; Brunner, Friedrich

    2002-04-01

    Oxygen-derived free radicals and oxidants (reactive oxygen intermediates, ROI) have been implicated in cardiovascular diseases. The protective role of nitric oxide (NO) against ROI-mediated tissue injury is not resolved. We tested the effects of exogenous NO, L- and D-arginine and a NO synthase inhibitor on electrolysis-induced cardiac injury and the generation of ROI by electrolysis. Superoxide dismutase (SOD) and catalase were used for comparison. Hearts ( n=7) from male rats (350+/-30 g) were perfused in vitro at 10 ml min(-1) g(-1), ROI generated by electrolysis of the perfusion medium (15 mA, 10 s), and cardiac function and the level of isoluminol-derived chemiluminescence in electrolysed perfusion medium documented for 15 min ( n=4). The ROI-induced maximal reduction of left ventricular developed pressure to 55+/-5% of baseline, and a 2.2+/-0.1-fold rise in coronary perfusion pressure 3 min after electrolysis, were prevented by SOD (50 U ml(-1)), catalase (100 U ml(-1)), S-nitroso- N-acetyl- D,L-penicillamine (SNAP, 100 nmol l(-1)); L-arginine (1 mmol l(-1)), N(G)-nitro- L-arginine (L-NNA, 200 micromol l(-1)) or D-arginine (1 mmol l(-1)). The effect of L-arginine was concentration dependent. In all cases, the beneficial effects were closely matched by a near-total reduction of ROI in the perfusion medium.We conclude that, besides mimicking or enhancing NO activity, L-arginine and donor-derived exogenous NO are cardioprotective by reducing ROI-mediated tissue injury. The protective effect of L-NNA and D-arginine implies that the protection results from a direct chemical interaction between the drug and the oxidizing species.

  12. Bi-enzyme L-arginine-selective amperometric biosensor based on ammonium-sensing polyaniline-modified electrode.

    PubMed

    Stasyuk, Nataliya; Smutok, Oleh; Gayda, Galina; Vus, Bohdan; Koval'chuk, Yevgen; Gonchar, Mykhailo

    2012-01-01

    A novel L-arginine-selective amperometric bi-enzyme biosensor based on recombinant human arginase I isolated from the gene-engineered strain of methylotrophic yeast Hansenula polymorpha and commercial urease is described. The biosensing layer was placed onto a polyaniline-Nafion composite platinum electrode and covered with a calcium alginate gel. The developed sensor revealed a good selectivity to L-arginine. The sensitivity of the biosensor was 110 ± 1.3 nA/(mM mm(2)) with the apparent Michaelis-Menten constant (K(M)(app)) derived from an L-arginine (L-Arg) calibration curve of 1.27 ± 0.29 mM. A linear concentration range was observed from 0.07 to 0.6mM, a limit of detection being 0.038 mM and a response time - 10s. The developed biosensor demonstrated good storage stability. A laboratory prototype of the proposed amperometric biosensor was applied to the samples of three commercial pharmaceuticals ("Tivortin", "Cytrarginine", "Aminoplazmal 10% E") for L-Arg testing. The obtained L-Arg-content values correlated well with those declared by producers. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Protective effect of quercetin and/or l-arginine against nano-zinc oxide-induced cardiotoxicity in rats

    NASA Astrophysics Data System (ADS)

    Faddah, L. M.; Baky, Nayira A. Abdel; Mohamed, Azza M.; Al-Rasheed, Nouf M.; Al-Rasheed, Nawal M.

    2013-04-01

    The aim of this study was to investigate the protective role of quercetin and/or l-arginine against the cardiotoxic potency of zinc oxide nanoparticle (ZnO-NP)-induced cardiac infarction. ZnO-NPs (50 nm) were administered orally at either 600 mg or 1 g/kg body weight for 5 consecutive days. The results revealed that co-administration of quercetin and/or l-arginine (each 200 mg/kg body weight) daily for 3 weeks to rats intoxicated by either of the two doses markedly ameliorated increases in serum markers of cardiac infarction, including troponin T, creatine kinase-MB, and myoglobin, as well as increases in proinflammatory biomarkers, including tumor necrosis factor-α, interleukin-6, and C-reactive protein, compared with intoxicated, untreated rats. Each agent alone or in combination also successfully modulated the alterations in serum vascular endothelial growth factor, cardiac calcium concentration, and oxidative DNA damage as well as the increase in the apoptosis marker caspase 3 of cardiac tissue in response to ZnO-NP toxicity. In conclusion, early treatment with quercetin and l-arginine may protect cardiac tissue from infarction induced by the toxic effects of ZnO-NPs.

  14. Acute effect of L-arginine on hemodynamics and vascular capacitance in the canine pacing model of heart failure.

    PubMed

    Ogilvie, R I; Zborowska-Sluis, D

    1995-09-01

    The effect of L-arginine, 250 mg/kg over 10 min, on hemodynamics and venous function was studied in nine splenectomized dogs under light pentobarbital anesthesia before and after 17 +/- 1 days of rapid right ventricular pacing (RRVP) at 250 beats/min. Chronic RRVP induced mild congestive heart failure with increased mean circulatory filling (Pmcf), right atrial (Pra) and pulmonary capillary wedge pressures (Ppcw), and reduced cardiac output (CO). During the development of heart failure, total vascular compliance assessed from Pmcf-blood volume relationships during circulatory arrest was unchanged, but total vascular capacitance was markedly reduced, with an increase in stressed and reduction in unstressed blood volumes. At baseline but not after RRVP, L-arginine increased CO and reduced pulmonary vascular resistance. There were no significant changes in Pra, Ppcw, or total peripheral resistance. L-Arginine failed to alter total vascular compliance and capacitance or central blood volume in the baseline or failure state. These results do not support the hypothesis that increased Pmcf and reduced total vascular capacitance in the early stages of pacing-induced heart failure are caused by reduced substrate availability for or an endogenous competitive antagonist of NO synthase in venous endothelial cells.

  15. Protective effect of L-carnitine and L-arginine against busulfan-induced oligospermia in adult rat.

    PubMed

    Abd-Elrazek, A M; Ahmed-Farid, O A H

    2018-02-01

    Busulfan is an anticancer drug caused variety of adverse effects for patients with cancer. But it could cause damage to the male reproductive system as one of its adverse effects. This study aimed to investigate the protective effect of L-carnitine and L-arginine on semen quality, oxidative stress parameters and testes cell energy after busulfan treatment. Adult male rats were divided into four groups: control (Con), busulfan (Bus), busulfan plus L-arginine (Bus + L-arg) and busulfan plus L-carnitine (Bus + L-car). After 28 days, the semen was collected from the epididymis and the testes were assessed. Sperm count, motility and velocity were measured by CASA, and smears were prepared for assessment of sperm morphology. Serum and testes supernatants were separated for DNA metabolites, oxidative stress and cell energy parameters. Testes tissues also subjected for caspase-3. The results showed significant improvement in sperm morphology, motility, velocity and count in the groups treated with L-arginine and L-carnitine and accompanied with an increase in MDA, GSSG and ATP, reduction in GSH, AMP, ADP, NO and 8-OHDG also recorded. These results are supported by caspase-3. Administration of L-arg and L-car attenuated the cytotoxic effects of busulfan by improving semen parameters, reducing oxidative stress and maintaining cell energy. © 2017 Blackwell Verlag GmbH.

  16. Thirteen-week oral toxicity study of L-arginine in rats.

    PubMed

    Tsubuku, Shoji; Hatayama, Kazuhisa; Mawatari, Kazunori; Smriga, Miro; Kimura, Takeshi

    2004-01-01

    The amino acid L-arginine (Arg) has been used extensively in dietary and pharmacological products. This study evaluated toxicological and behavioral effects of Arg produced by Ajinomoto Co. (Tokyo, Japan) during a dosing study with male and female Sprague-Dawley rats. The amino acid was incorporated into a standard diet at doses equal to 1.25%, 2.5%, and 5.0% (w/w). A control group of rats received only a standard diet. All diets were administered ad libitum for 13 continuous weeks. To examine recoverability of any potential effects, the administration period was followed by a 5-week-long recovery, during which only a standard diet was provided. In male and female rats in each concentration group, treatment-related changes were not observed for clinical signs, body weights, diet consumption, ophthalmology, gross pathology, organ weight, or histopathology. An elevated level of plasma glucose was detected in some male rats (5.0%, w/w) during the analysis conducted in the fifth week of administration; however, the degree of the change was within the physiological range, and no changes were observed at the end of the administration period. In the same group, an increase in hemoglobin, together with a tendency toward an increase in the red blood cell counts, was found, but the change was considered toxicologically insignificant. The no-observed-adverse-effect level (NOAEL) for Arg was estimated at 5.0% (w/w) for both genders (males, 3.3 +/- 0.1 g/kg/day; females, 3.9 +/- 0.2 g/kg/day).

  17. In ovo feeding of L-arginine alters energy metabolism in post-hatch broilers.

    PubMed

    Yu, L L; Gao, T; Zhao, M M; Lv, P A; Zhang, L; Li, J L; Jiang, Y; Gao, F; Zhou, G H

    2018-01-01

    This study aimed to investigate the effects of in ovo feeding (IOF) of L-arginine (Arg) on energy metabolism in post-hatch broilers. A total of 720 eggs was randomly assigned to 3 treatments: 1) non-injected control group, 2) 0.75% NaCl diluent-injected control group, and 3) 1.0% Arg solution-injected group. At 17.5 d of incubation, 0.6 mL of each solution was injected into the amniotic fluid of each egg of injected groups. After hatching, 80 male chicks were randomly assigned to each treatment group with 8 replicates per group. The results showed that IOF of Arg increased glycogen and glucose concentrations in the liver and pectoral muscle of broilers at hatch (P < 0.05). The plasma glucose and insulin levels were higher in the Arg group than in the non-injected and diluent-injected control groups (P < 0.05). Meanwhile, IOF of Arg enhanced the hepatic glucose-6-phosphatase (G6P) activity at hatch (P < 0.05). There was no difference in hexokinase (HK) or phosphofructokinase (PFK) enzyme activities in the pectoral muscle in all groups. Further, IOF of Arg increased the phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1,6-bisphosphatase (FBP) mRNA expressions at hatch (P < 0.05). In addition, broilers in the Arg group had a higher mRNA expression of glycogen synthase and a lower expression of glycogen phosphorylase in the liver and pectoral muscles than in the non-injected controls at hatch (P < 0.05). In conclusion, IOF of Arg solution enhanced liver and pectoral muscle energy reserves at hatch, which might be considered as an effective strategy for regulating early energy metabolism in broilers. © 2017 Poultry Science Association Inc.

  18. Hydrogen-rich saline ameliorates the severity of L-arginine-induced acute pancreatitis in rats

    SciTech Connect

    Chen, Han; Sun, Yan Ping; Li, Yang

    2010-03-05

    Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the L-arginine (L-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of L-Arg, each at concentrations of 250 mg/100 g body weight, with an interval of 1 h. Hydrogen-rich saline (>0.6 mM, 6 ml/kg) or saline (6 ml/kg) was administered, respectively, via tail vein 15 min after each L-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreasmore » were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-{kappa}B) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of L-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-{kappa}B activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-{kappa}B activation and to promote acinar cell proliferation.« less

  19. Morphological and immunobiochemical analysis of the liver in L-arginine induced experimental chronic pancreatitis.

    PubMed

    Hu, Na; Shen, Yicong; Liu, Fengyu; Wu, Jiuping; Yuan, Feng; Tian, Liwei; Wu, Bo; Chen, Guoqing; Zhang, Jianming; Wang, Jun

    Clinical evidence indicates that hepatic abnormalities in patients with chronic pancreatitis are not uncommon. Here we aimed to study the possible association between liver and pancreatic damage in a recently described experimental mouse model of CP. The severity of the damage to pancreas, liver and other organs was assessed by biochemical markers and histopathology. The methods applied included Hematoxylin Eosin staining, electron microscope examination, biochemical measurements, RT-PCR, ELISA, and the correlations among some of the parameters contributing to these changes were statistically analyzed. The hepatic aberrations were mainly represented by mild infiltration of inflammatory cells in portal triad and congestion of central vein of liver, and the main features of drug-induced hepatotoxicity could not be observed. Severe fibrosis of pancreatic tissue was noticed in experimental group, and the existence of multiple organ injuries was also seen under the microscope. Hepatic pathologic scores were positively correlated with those from the corresponding pancreatic specimens (r = 0.72, P < 0.01). TGF-β1 protein levels significantly elevated both in the test pancreas and liver (P < 0.05) and these values were positively correlated (r = 0.86, P < 0.01). The level of interleukin-1β was increased in the serum and tissue of the liver. In addition, cardiac troponin (Tn-I) level not only significantly increased in myocardial homogenates (P < 0.05) but also was positively correlated with the corresponding pathologic score of the liver (r = 0.88, P < 0.01). The liver aberrations might be associated with L-arginine induced chronic pancreatitis. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  20. Metabolic engineering of microorganisms for the production of L-arginine and its derivatives.

    PubMed

    Shin, Jae Ho; Lee, Sang Yup

    2014-12-03

    L-arginine (ARG) is an important amino acid for both medicinal and industrial applications. For almost six decades, the research has been going on for its improved industrial level production using different microorganisms. While the initial approaches involved random mutagenesis for increased tolerance to ARG and consequently higher ARG titer, it is laborious and often leads to unwanted phenotypes, such as retarded growth. Discovery of L-glutamate (GLU) overproducing strains and using them as base strains for ARG production led to improved ARG production titer. Continued effort to unveil molecular mechanisms led to the accumulation of detailed knowledge on amino acid metabolism, which has contributed to better understanding of ARG biosynthesis and its regulation. Moreover, systems metabolic engineering now enables scientists and engineers to efficiently construct genetically defined microorganisms for ARG overproduction in a more rational and system-wide manner. Despite such effort, ARG biosynthesis is still not fully understood and many of the genes in the pathway are mislabeled. Here, we review the major metabolic pathways and its regulation involved in ARG biosynthesis in different prokaryotes including recent discoveries. Also, various strategies for metabolic engineering of bacteria for the overproduction of ARG are described. Furthermore, metabolic engineering approaches for producing ARG derivatives such as L-ornithine (ORN), putrescine and cyanophycin are described. ORN is used in medical applications, while putrescine can be used as a bio-based precursor for the synthesis of nylon-4,6 and nylon-4,10. Cyanophycin is also an important compound for the production of polyaspartate, another important bio-based polymer. Strategies outlined here will serve as a general guideline for rationally designing of cell-factories for overproduction of ARG and related compounds that are industrially valuable.

  1. L-arginine and arginine analogues: effects on isolated blood vessels and cultured endothelial cells.

    PubMed Central

    Schmidt, H. H.; Baeblich, S. E.; Zernikow, B. C.; Klein, M. M.; Böhme, E.

    1990-01-01

    1. The present study examined effects of arginine (Arg) and various Arg analogues on the vascular tone of rabbit and rat aortic rings, the release of nitrite from cultured bovine aortic endothelial cells and the metabolism of L-Arg in bovine and porcine endothelial cell homogenates. The respective D-enantiomers or N-alpha-benzoyl-L-arginine ethyl ester did not substitute for L-Arg. 2. In bovine aortic endothelial cells, the release of nitrite was only observed in the presence of L-Arg or L-Arg methyl ester in the cell culture medium. 3. In dialyzed homogenates of porcine and bovine aortic endothelial cells, L-Arg was metabolized independently of NADPH and Ca2+ to yield L-ornithine (L-Orn) and L-citrulline (L-Cit). No concomitant nitrite formation was detected. 4. Pretreatment of rabbit and rat aortic rings with L-canavanine (L-Can) or NG-monomethyl-L-Arg (L-NMMA) inhibited ATP- and acetylcholine-induced relaxations (endothelium-dependent) but not glyceryltrinitrate-induced relaxations (endothelium-independent). 5. In rabbit aortic rings, Arg and monomeric Arg analogues induced endothelium-independent relaxations. L-Arg methyl ester induced an endothelium-independent contraction, and L-NMMA induced a relaxation in the absence of endothelium and a contraction in the presence of endothelium. Polymeric basic amino acids such as poly L-Arg induced endothelium-dependent relaxations (inhibited by L-Can), a subsequent refractoriness to endothelium-dependent vasodilators (not prevented by L-Can) and endothelial cell death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2282457

  2. Hypermagnesemia disturbances in rats, NO-related: pentadecapeptide BPC 157 abrogates, L-NAME and L-arginine worsen.

    PubMed

    Medvidovic-Grubisic, Maria; Stambolija, Vasilije; Kolenc, Danijela; Katancic, Jadranka; Murselovic, Tamara; Plestina-Borjan, Ivna; Strbe, Sanja; Drmic, Domagoj; Barisic, Ivan; Sindic, Aleksandra; Seiwerth, Sven; Sikiric, Predrag

    2017-08-01

    Stable gastric pentadecapeptide BPC 157, administered before a high-dose magnesium injection in rats, might be a useful peptide therapy against magnesium toxicity and the magnesium-induced effect on cell depolarization. Moreover, this might be an NO-system-related effect. Previously, BPC 157 counteracts paralysis, arrhythmias and hyperkalaemia, extreme muscle weakness; parasympathetic and neuromuscular blockade; injured muscle healing and interacts with the NOS-blocker and NOS-substrate effects. Assessment included magnesium sulfate (560 mg/kg intraperitoneally)-induced muscle weakness, muscle and brain lesions, hypermagnesemia, hyperkalaemia, increased serum enzyme values assessed in rats during and at the end of a 30-min period and medication (given intraperitoneally/kg at 15 min before magnesium) [BPC 157 (10 µg, 10 ng), L-NAME (5 mg), L-arginine (100 mg), alone and/or together]. In HEK293 cells, the increasing magnesium concentration from 1 to 5 mM could depolarize the cells at 1.75 ± 0.44 mV. L-NAME + magnesium-rats and L-arginine + magnesium-rats exhibited worsened severe muscle weakness and lesions, brain lesions, hypermagnesemia and serum enzymes values, with emerging hyperkalaemia. However, L-NAME + L-arginine + magnesium-rats exhibited all control values and normokalaemia. BPC 157 abrogated hypermagnesemia and counteracted all of the magnesium-induced disturbances (including those aggravated by L-NAME or L-arginine). Thus, cell depolarization due to increasing magnesium concentration was inhibited in the presence of BPC 157 (1 µM) in vitro. BPC 157 likely counteracts the initial event leading to hypermagnesemia and the life-threatening actions after a magnesium overdose. In contrast, a worsened clinical course, higher hypermagnesemia, and emerging hyperkalaemia might cause both L-NAME and L-arginine to affect the same events adversely. These events were also opposed by BPC 157.

  3. Involvement of l-arginine-nitric oxide pathway in anxiolytic-like effects of zinc chloride in rats.

    PubMed

    Navabi, Seyedeh Parisa; Eshagh Harooni, Hooman; Moazedi, Ahmad Ali; Khajepour, Lotfolah; Fathinia, Kosar

    2016-10-01

    Zinc is crucial for normal development of the brain, and Zinc deficiency has been shown to associate with neurological disorders (e.g. anxiety) through interactions with several neurotransmitter systems such as nitric oxide (NO). In this regard, our study aimed to evaluate the possible involvement of l-arginine NO pathway on anxiolytic effects of zinc in adult male rats. Zinc chloride at doses of 2.5 and 10mg/kg (intraperitoneal or ip) or saline (1ml/kg, ip) were injected 30min before the anxiety test. Zinc administrated rats (10mg/kg) were pre-treated with intra-CA1 microinjection of l-arginine in sub-effective dose of 1μg/rat (dorsal hippocampus, vehicle: saline1μl/rat). In addition, zinc chloride and NG-nitro-l-arginine methyl ester (l-NAME) were intraperitoneally co-administrated in sub-effective doses of 2.5mg/kg and 80mg/kg, respectively. The percentage of open arm time (OAT%), percentage of open arm entry (OAE%), as measures of anxiety, and total number of arm entries, as measures of locomotor activity, were recorded. Treatment with zinc (10mg/kg) markedly produced an increase in OAT% and OAE% in the Elevated plus maze test (EPM). A decrease of OAT% and OAE% was shown in groups which received zinc (10mg/kg) and l-arginine (1μg/rat) concomitantly as compared to the control group. Moreover, an increase of OAE% was revealed in the group exposed to Zinc (2.5mg/kg) and l-NAME (80mg/kg) co-administration. Although, Two-way ANOVA showed no significant differences of anxiety indices in rats received drug+zinc chloride in compare to the zinc pretreated with saline group. Anxiolytic- like effect of zinc reversed by nitric oxide precursor l-arginine. Additionally, the synergistic effects of l-NAME and ZnCl 2 were shown in the EPM. Thus our findings suggest that at least in part the anxiolytic effects of zinc can be mediated through the nitric oxide system. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME

    PubMed Central

    Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Bauk, Lara; Sever, Marko; Zenko Sever, Anita; Luetic, Kresimir; Suran, Jelena; Seiwerth, Sven; Sikiric, Predrag

    2017-01-01

    AIM To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODS Celecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. RESULTS This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). CONCLUSION BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post-surgery application and NO system involvement. PMID:28839430

  5. Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME.

    PubMed

    Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Bauk, Lara; Sever, Marko; Zenko Sever, Anita; Luetic, Kresimir; Suran, Jelena; Seiwerth, Sven; Sikiric, Predrag

    2017-08-07

    To counteract/reveal celecoxib-induced toxicity and NO system involvement. Celecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs' post-surgery application and NO system involvement.

  6. Time-dependent alterations in serum NO concentration after oral administration of l-arginine, l-NAME, and allopurinol in intestinal ischemia/reperfusion

    PubMed Central

    Yanni, Amalia E; Margaritis, Eleutherios; Liarakos, Nikolaos; Pantopoulou, Alkisti; Poulakou, Maria; Kostakis, Maria; Perrea, Despoina; Kostakis, Alkis

    2008-01-01

    Objective To study the effect of oral administration of a nitric oxide (NO) donor l-arginine (l-Arg), a NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) and an inhibitor of xanthine oxidase, allopurinol (Allo), on serum NO concentration and catalase activity after intestinal ischemia/reperfusion (I/R) in rats. Methods Male Wistar rats received per os l-Arg (800 mg/kg) or l-NAME (50 mg/kg) or Allo (100 mg/kg) 24 hrs, 12 hrs and 1 hr before underwent 1 hr occlusion of superior mesenteric artery followed by 1 hr of reperfusion (l-Arg(IR1), l-NAME(IR1) and Allo(IR1) respectively) or 1 hr occlusion followed by 8 hrs of reperfusion (l-Arg(IR8), l-NAME(IR8) and Allo(IR8) respectively). There was one group underwent 1 hr occlusion (I), a group underwent 1 hr occlusion followed by 1 hr reperfusion (IR1), a group subjected to 1 hr occlusion followed by 8 hrs of reperfusion (IR8) and a last group that served as control (C). Serum NO concentration and catalase activity were measured. Results After 1 hr of reperfusion serum NO concentration was elevated in IR1 and l-Arg(IR1) groups compared with group C but not in l-NAME(IR1) and Allo(IR1) group. Catalase activity was enhanced in l-NAME(IR1) group. Interestingly, serum NO concentration was increased after 8 hrs of reperfusion in all groups (IR8, l-Arg(IR8), l-NAME(IR8) and Allo(IR8)) compared with control while catalase activity did not show significant difference in any group. Conclusions The results of the present study show that NO concentration is elevated in serum after intestinal I/R and the elevation sustained after administration of l-Arg but not after administration of l-NAME or Allo after 1 hr reperfusion. However, after 8 hrs of reperfusion NO concentration was increased in all groups studied, focusing attention on its possible important role in a complicated situation such as intestinal I/R that involves intestine and other organs. Serum catalase activity does not seem to be affected by per os

  7. N-hydroxylamine is not an intermediate in the conversion of L-arginine to an activator of soluble guanylate cyclase in neuroblastoma N1E-115 cells.

    PubMed Central

    Pou, S; Pou, W S; Rosen, G M; el-Fakahany, E E

    1991-01-01

    This study evaluates the role of N-hydroxylamine (NH2OH) in activating soluble guanylate cyclase in the mouse neuroblastoma clone N1E-115. It has been proposed that NH2OH is a putative intermediate in the biochemical pathway for the generation of nitric oxide (NO)/endothelium-derived relaxing factor (EDRF) from L-arginine. NH2OH caused a time- and concentration-dependent increase in cyclic GMP formation in intact cells. This response was not dependent on Ca2+. In cytosol preparations the activation of guanylate cyclase by L-arginine was dose-dependent and required Ca2+ and NADPH. In contrast, NH2OH itself did not activate cytosolic guanylate cyclase but it inhibited the basal activity of this enzyme in a concentration-dependent manner. The formation of cyclic GMP in the cytosolic fractions in response to NH2OH required the addition of catalase and H2O2. On the other hand, catalase and/or H2O2 lead to a decrease in L-arginine-induced cyclic GMP formation. Furthermore, NH2OH inhibited L-arginine- and sodium nitroprusside-induced cyclic GMP formation in the cytosol. The inhibition of L-arginine-induced cyclic GMP formation in the cytosol by NH2OH was not reversed by the addition of superoxide dismutase. These data strongly suggest that NH2OH is not a putative intermediate in the metabolism of L-arginine to an activator of guanylate cyclase. PMID:1671745

  8. Effect of Exercise Training and L-arginine on Oxidative Stress and Left Ventricular Function in the Post-ischemic Failing Rat Heart.

    PubMed

    Ranjbar, Kamal; Nazem, Farzad; Nazari, Afshin

    2016-04-01

    The aim of the present study was to evaluate the effect of exercise training (ET) and L-arginine on oxidative stress and ventricular function in rat with myocardial infarction (MI). Four weeks after the surgical procedures, 40 Wistar male rats were randomized to the following groups: MI-sedentary (Sed); MI-exercise (Ex); MI-sedentary + L-arginine (Sed + LA); and MI-exercise + L-arginine (Ex + LA); the rats were subjected to aerobic training in the form of treadmill running. Rats in the L-arginine-treated groups drank water containing 4 % L-arginine. Before and after the training program, all subjects underwent resting echocardiography. Catalase (CAT) glutathione peroxidase (GPx), malondialdehyde (MDA) and myeloperoxidase (MPO) were measured. Cardiac output, stroke volume and fractional shortening in Ex and Ex + LA groups significantly increased in comparison with the Sed group. Cardiac systolic function indices in Ex + LA group were significantly greater than Ex group. Also, GPx activity and MDA, respectively, increased and decreased in response to ET, but no change was observed in MPO and CAT. These results suggest that ET increased LV function by decreasing oxidative stress and increasing antioxidant defense system in rats with MI. In addition in response to training, L-arginine appears to have additive effect on cardiac function, but have no effect on oxidative stress indices.

  9. KDP crystal doped with L-arginine amino acid: growth, structure perfection, optical and strength characteristics

    NASA Astrophysics Data System (ADS)

    Pritula, I. M.; Kostenyukova, E. I.; Bezkrovnaya, O. N.; Kolybaeva, M. I.; Sofronov, D. S.; Dolzhenkova, E. F.; Kanaev, A.; Tsurikov, V.

    2016-07-01

    Potassium Dihydrogen Phosphate (KDP) crystal doped with L-arginine (L-arg) amino acid with 1.4 wt% concentration in the solution was grown onto a point seed by the method of temperature reduction. For the first time an attempt was made to grow large-size (7 × 6 × 8 cm3) optically transparent crystals, which allowed to analyze the effect of L-arg additive on the physical properties of the different growth sectors ({100} and {101}) of KDP. The incorporation of L-arg into both growth sectors of the crystal was confirmed by the methods of optical and IR spectroscopy and found to be caused by the ability of the amino acid to form hydrogen bonds with the face {100} and electrostatically interact with the positively charged face {101} of KDP crystal. A slight variation in the unit cell parameters was reported, the elementary cell volume of KDP:L-arg crystal increased in comparison with the one of pure KDP by 2·10-2 and 2.07·10-2 Å3 in the sectors {100} and {101}, respectively. It was found that the doping of L-arg enhanced the SHG efficiency of KDP and depended on the crystal growth sectors. The SHG efficiency of KDP:L-arg was by a factor 2.53 and 3.95 higher in comparison with those of pure KDP for {101} and {100} growth sector, respectively. The doping was found to lead to softening of both faces by ∼3-10% and ∼14-17% in the sectors {101} and {100}, respectively. Investigation of the influence of L-arg molecules on the bulk laser damage threshold of the crystals showed that the bulk laser damage threshold of the samples of KDP:L-arg crystal was higher than the one of the pure crystal in the sector {101} and lower in the sector {100}. The correlation between microhardness and laser damage threshold were discussed. The study is helpful for further searching, designing and simulation of hybrid NLO materials.

  10. Reengineering of a Corynebacterium glutamicum L-arginine and L-citrulline producer.

    PubMed

    Ikeda, Masato; Mitsuhashi, Satoshi; Tanaka, Kenji; Hayashi, Mikiro

    2009-03-01

    Toward the creation of a robust and efficient producer of L-arginine and L-citrulline (arginine/citrulline), we have performed reengineering of a Corynebacterium glutamicum strain by using genetic information of three classical producers. Sequence analysis of their arg operons identified three point mutations (argR123, argG92(up), and argG45) in one producer and one point mutation (argB26 or argB31) in each of the other two producers. Reconstitution of the former three mutations or of each argB mutation on a wild-type genome led to no production. Combined introduction of argB26 or argB31 with argR123 into a wild type gave rise to arginine/citrulline production. When argR123 was replaced by an argR-deleted mutation (Delta argR), the production was further increased. The best mutation set, Delta argR and argB26, was used to screen for the highest productivity in the backgrounds of different wild-type strains of C. glutamicum. This yielded a robust producer, RB, but the production was still one-third of that of the best classical producer. Transcriptome analysis revealed that the arg operon of the classical producer was much more highly upregulated than that of strain RB. Introduction of leuC456, a mutation derived from a classical L-lysine producer and provoking global induction of the amino acid biosynthesis genes, including the arg operon, into strain RB led to increased production but incurred retarded fermentation. On the other hand, replacement of the chromosomal argB by heterologous Escherichia coli argB, natively insensitive to arginine, caused a threefold-increased production without retardation, revealing that the limitation in strain RB was the activity of the argB product. To overcome this, in addition to argB26, the argB31 mutation was introduced into strain RB, which caused higher deregulation of the enzyme and resulted in dramatically increased production, like the strain with E. coli argB. This reconstructed strain displayed an enhanced performance

  11. Dose-Dependent Effects of L-Arginine on PROP Bitterness Intensity and Latency and Characteristics of the Chemical Interaction between PROP and L-Arginine.

    PubMed

    Melis, Melania; Arca, Massimiliano; Aragoni, Maria Carla; Cabras, Tiziana; Caltagirone, Claudia; Castagnola, Massimo; Crnjar, Roberto; Messana, Irene; Tepper, Beverly J; Tomassini Barbarossa, Iole

    2015-01-01

    Genetic variation in the ability to taste the bitterness of 6-n-propylthiouracil (PROP) is a complex trait that has been used to predict food preferences and eating habits. PROP tasting is primarily controlled by polymorphisms in the TAS2R38 gene. However, a variety of factors are known to modify the phenotype. Principle among them is the salivary protein Ps-1 belonging to the basic proline-rich protein family (bPRP). Recently, we showed that oral supplementation with Ps-1 as well as its related free amino acids (L-Arg and L-Lys) enhances PROP bitterness perception, especially for PROP non-tasters who have low salivary levels of Ps-1. Here, we show that salivary L-Arg levels are higher in PROP super-tasters compared to medium tasters and non-tasters, and that oral supplementation with free L-Arg enhances PROP bitterness intensity as well as reduces bitterness latency in a dose-dependent manner, particularly in individuals with low salivary levels of both free L-Arg and Ps-1 protein. Supplementation with L-Arg also enhanced the bitterness of caffeine. We also used 1H-NMR spectroscopy and quantum-mechanical calculations carried out by Density Functional Theory (DFT) to characterize the chemical interaction between free L-Arg and the PROP molecule. Results showed that the -NH2 terminal group of the L-ArgH+ side chain interacts with the carbonyl or thiocarbonyl groups of PROP by forming two hydrogen bonds with the resulting charged adduct. The formation of this PROP•ArgH+ hydrogen-bonded adduct could enhance bitterness intensity by increasing the solubility of PROP in saliva and its availability to receptor sites. Our data suggest that L-Arg could act as a 'carrier' of various bitter molecules in saliva.

  12. Dose-Dependent Effects of L-Arginine on PROP Bitterness Intensity and Latency and Characteristics of the Chemical Interaction between PROP and L-Arginine

    PubMed Central

    Melis, Melania; Arca, Massimiliano; Aragoni, Maria Carla; Cabras, Tiziana; Caltagirone, Claudia; Castagnola, Massimo; Crnjar, Roberto; Messana, Irene; Tepper, Beverly J.; Tomassini Barbarossa, Iole

    2015-01-01

    Genetic variation in the ability to taste the bitterness of 6-n-propylthiouracil (PROP) is a complex trait that has been used to predict food preferences and eating habits. PROP tasting is primarily controlled by polymorphisms in the TAS2R38 gene. However, a variety of factors are known to modify the phenotype. Principle among them is the salivary protein Ps-1 belonging to the basic proline-rich protein family (bPRP). Recently, we showed that oral supplementation with Ps-1 as well as its related free amino acids (L-Arg and L-Lys) enhances PROP bitterness perception, especially for PROP non-tasters who have low salivary levels of Ps-1. Here, we show that salivary L-Arg levels are higher in PROP super-tasters compared to medium tasters and non-tasters, and that oral supplementation with free L-Arg enhances PROP bitterness intensity as well as reduces bitterness latency in a dose-dependent manner, particularly in individuals with low salivary levels of both free L-Arg and Ps-1 protein. Supplementation with L-Arg also enhanced the bitterness of caffeine. We also used 1H-NMR spectroscopy and quantum-mechanical calculations carried out by Density Functional Theory (DFT) to characterize the chemical interaction between free L-Arg and the PROP molecule. Results showed that the –NH2 terminal group of the L-ArgH+ side chain interacts with the carbonyl or thiocarbonyl groups of PROP by forming two hydrogen bonds with the resulting charged adduct. The formation of this PROP•ArgH+ hydrogen-bonded adduct could enhance bitterness intensity by increasing the solubility of PROP in saliva and its availability to receptor sites. Our data suggest that L-Arg could act as a ‘carrier’ of various bitter molecules in saliva. PMID:26103639

  13. Dietary arginine supplementation affects microvascular development in the small intestine of early-weaned pigs.

    PubMed

    Zhan, Zhenfeng; Ou, Deyuan; Piao, Xiangshu; Kim, Sung Woo; Liu, Yanhong; Wang, Junjun

    2008-07-01

    This study was conducted to evaluate the effects of dietary arginine levels on microvascular development of the small intestine in early-weaned pigs. Twenty-four crossbred pigs (5.0 +/- 0.3 kg body weight) were individually housed and randomly allotted to 1 of 3 diets supplemented with 0, 0.7, and 1.2% L-arginine (8 pigs per group). Pigs consumed the diets ad libitum for 10 d. We collected blood samples on d 3, 6, and 10. On d 10, 6 pigs from each group were randomly selected and killed for tissue sample collection. Compared with control pigs, dietary supplementation with 0.7% L-arginine increased (P < 0.05) jejunal concentrations of nitrite and nitrate (stable oxidation products of nitric oxide), intestinal villus height, as well as plasma proline and arginine concentrations on d 6 and 10. Dietary supplementation with 0.7% L-arginine also increased (P < 0.05) immunoreactive expression of CD34 in duodenal submucosa, ileal mucosa and submucosa, and expression of vascular endothelial growth factor (VEGF) in duodenal submucosa, jejunal mucosa and submucosa, and ileal mucosa compared with the control and 1.2% L-arginine supplementation. Dietary supplementation with 1.2% L-arginine increased (P < 0.05) the concentration of jejunal endothelin-1 compared with the control pigs. Immunoexpression of VEGF in duodenal mucosa and plasma lysine concentrations on d 6 and 10 were lower (P < 0.05) in pigs supplemented with 1.2% L-arginine than in unsupplemented pigs. Collectively, these findings indicate that the effects of L-arginine on microvascular development are beneficial at lower levels but have adverse effects at higher intakes. Dietary supplementation with 0.7% L-arginine may be a useful method to improve microvascular development in the small intestine of early-weaned pigs.

  14. Inhibition of nitric oxide synthase abrogates lipopolysaccharides-induced up-regulation of L-arginine uptake in rat alveolar macrophages

    PubMed Central

    Hammermann, Rainer; Stichnote, Christina; Closs, Ellen Ildicho; Nawrath, Hermann; Racké, Kurt

    2001-01-01

    It was tested whether the inducible nitric oxide synthase (iNOS) pathway might be involved in lipopolysaccharides-(LPS)-induced up-regulation of L-arginine transport in rat alveolar macrophages (AMΦ). AMΦ were cultured in absence or presence of LPS. Nitrite accumulation was determined in culture media and cells were used to study [3H]-L-arginine uptake or to isolate RNA for RT – PCR. Culture in presence of LPS (1 μg ml−1, 20 h) caused 11 fold increase of nitrite accumulation and 2.5 fold increase of [3H]-L-arginine uptake. The inducible NO synthase (iNOS) inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT) present alone during culture had only marginal effects on [3H]-L-arginine uptake. However, AMT present during culture additionally to LPS, suppressed LPS-induced nitrite accumulation and LPS-stimulated [3H]-L-arginine uptake in the same concentration-dependent manner. AMT present only for the last 30 min of the culture period had similar effects on [3H]-L-arginine uptake. AMT present only during the uptake period also inhibited LPS-stimulated [3H]-L-arginine uptake, but with lower potency. The inhibitory effect of AMT could not be opposed by the NO releasing compound DETA NONOate. LPS caused an up-regulation of the mRNA for the cationic amino acid transporter CAT-2B, and this effect was not affected by AMT. AMT (100 μM) did not affect L-arginine transport studied by electrophysiological techniques in Xenopus laevis oocytes expressing either the human cationic amino acid transporter hCAT-1 or hCAT-2B. In conclusion, iNOS inhibition in rat AMΦ abolished LPS-activated L-arginine uptake. This effect appears to be caused by reduced flow of L-arginine through the iNOS pathway. PMID:11375254

  15. The L-arginine/asymmetric dimethylarginine ratio is improved by anti-tumor necrosis factor-α therapy in inflammatory arthropathies. Associations with aortic stiffness.

    PubMed

    Angel, Kristin; Provan, Sella Aarrestad; Mowinckel, Petter; Seljeflot, Ingebjørg; Kvien, Tore Kristian; Atar, Dan

    2012-11-01

    Anti-Tumor Necrosis Factor (TNF)-α therapy improves vascular pathology in inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The l-arginine/ADMA ratio is important for modulation of the nitric oxide synthase activity. We examined the effect of TNF-α antagonists on ADMA and l-arginine/ADMA, and associations between ADMA, L-arginine/ADMA, aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies. Forty-eight patients who started with anti-TNF-α therapy were compared with a non-treated group of 32 patients. Plasma ADMA and L-arginine were assessed at baseline, 3 and 12 months. In a subgroup of 55 patients, aortic pulse wave velocity (aPWV) was measured at baseline, 3 and 12 moths, and CIMT was examined at baseline and 12 months. Anti-TNF-α therapy increased the L-arginine/ADMA ratio (mean [SD]) in the treatment group compared to the control group after 3 months (12 [29] vs. -13 [20], P < 0.001) and 12 months (7 [27] vs. -8 [19], P = 0.008), but did not affect ADMA (3 months: 0.00 [0.09] μmol/L vs. 0.02 [0.07] μmol/L, P = 0.42, 12 months: 0.01 [0.08] μmol/L vs. 0.01 [0.09] μmol/L, P = 0.88). Baseline aPWV was associated with ADMA (P = 0.02) and L-arginine/ADMA (P = 0.02) in multiple regression analyses, and the L-arginine/ADMA ratio was continuously associated with aPWV after initiation of anti-TNF-α therapy (P = 0.03). ADMA and L-arginine/ADMA were not correlated with CIMT. Anti-TNF-α therapy improved the L-arginine/ADMA ratio in patients with inflammatory arthropathies. ADMA and the L-arginine/ADMA ratio were associated with aPWV, and might have a mechanistic role in the aortic stiffening observed in these patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine

    PubMed Central

    Lüneburg, Nicole; Lieb, Wolfgang; Zeller, Tanja; Chen, Ming-Huei; Maas, Renke; Carter, Angela M.; Xanthakis, Vanessa; Glazer, Nicole L; Schwedhelm, Edzard; Seshadri, Sudha; Ikram, M. Arfan; Longstreth, W.T.; Fornage, Myriam; König, Inke R.; Loley, Christina; Ojeda, Francisco M.; Schillert, Arne; Wang, Thomas J.; Sticht, Heinrich; Kittel, Anja; König, Jörg; Benjamin, Emelia J.; Sullivan, Lisa M.; Bernges, Isabel; Anderssohn, Maike; Ziegler, Andreas; Gieger, Christian; Illig, Thomas; Meisinger, Christa; Wichmann, H.-Erich; Wild, Philipp S.; Schunkert, Heribert; Psaty, Bruce M.; Wiggins, Kerri L.; Heckbert, Susan R.; Smith, Nicholas; Lackner, Karl; Lunetta, Kathryn L.; Blankenberg, Stefan; Erdmann, Jeanette; Munzel, Thomas; Grant, Peter J.; Vasan, Ramachandran S.; Böger, Rainer H.

    2016-01-01

    Background Dimethylarginines (DMA) interfere with nitric oxide (NO) formation by inhibiting NO synthase (asymmetric dimethylarginine, ADMA) and L-arginine uptake into the cell (ADMA and symmetric dimethylarginine, SDMA). In prospective clinical studies ADMA has been characterized as a cardiovascular risk marker whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterise the environmental and genetic contributions to inter-individual variability of these biomarkers. Methods and Results This study comprised a genome-wide association analysis of 3 well-characterized population-based cohorts (FHS (n=2992), GHS (n=4354) and MONICA/KORA F3 (n=581)) and identified replicated loci (DDAH1, MED23, Arg1 and AGXT2) associated with the inter-individual variability in ADMA, L-arginine and SDMA. Experimental in-silico and in-vitro studies confirmed functional significance of the identified AGXT2 variants. Clinical outcome analysis in 384 patients of the Leeds stroke study demonstrated an association between increased plasma levels of SDMA, AGXT2 variants and various cardiometabolic risk factors. AGXT2 variants were not associated with post-stroke survival in the Leeds study, nor were they associated with incident stroke in the CHARGE consortium. Conclusion These GWAS support the importance of DDAH1 and MED23/Arg1 in regulating ADMA and L-arginine metabolism, respectively, and identify a novel regulatory renal pathway for SDMA by AGXT2. AGXT2 variants might explain part of the pathogenic link between SDMA, renal function, and outcome. An association between AGXT2 variants and stroke is unclear and warrants further investigation. PMID:25245031

  17. Insulin restores L-arginine transport requiring adenosine receptors activation in umbilical vein endothelium from late-onset preeclampsia.

    PubMed

    Salsoso, R; Guzmán-Gutiérrez, E; Sáez, T; Bugueño, K; Ramírez, M A; Farías, M; Pardo, F; Leiva, A; Sanhueza, C; Mate, A; Vázquez, C; Sobrevia, L

    2015-03-01

    Preeclampsia is associated with impaired placental vasodilation and reduced endothelial nitric oxide synthase (eNOS) activity in the foetoplacental circulation. Adenosine and insulin stimulate vasodilation in endothelial cells, and this activity is mediated by adenosine receptor activation in uncomplicated pregnancies; however, this activity has yet to be examined in preeclampsia. Early onset preeclampsia is associated with severe placental vasculature alterations that lead to altered foetus growth and development, but whether late-onset preeclampsia (LOPE) alters foetoplacental vascular function is unknown. Vascular reactivity to insulin (0.1-1000 nmol/L, 5 min) and adenosine (1 mmol/L, 5 min) was measured in KCl-preconstricted human umbilical vein rings from normal and LOPE pregnancies using a wire myograph. The protein levels of human cationic amino acid transporter 1 (hCAT-1), adenosine receptor subtypes, total and Ser¹¹⁷⁷- or Thr⁴⁹⁵-phosphorylated eNOS were detected via Western blot, and L-arginine transport (0-1000 μmol/L L-arginine, 3 μCi/mL L-[³H]arginine, 20 s, 37 °C) was measured in the presence or absence of insulin and adenosine receptor agonists or antagonists in human umbilical vein endothelial cells (HUVECs) from normal and LOPE pregnancies. LOPE increased the maximal L-arginine transport capacity and hCAT-1 and eNOS expression and activity compared with normal conditions. The A(2A) adenosine receptor (A(2A)AR) antagonist ZM-241385 blocked these effects of LOPE. Insulin-mediated umbilical vein ring relaxation was lower in LOPE pregnancies than in normal pregnancies and was restored using the A(2A)AR antagonist. The reduced foetoplacental vascular response to insulin may result from A(2A)AR activation in LOPE pregnancies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Non-invasive measurement of the haemodynamic effects of inhaled salbutamol, intravenous L-arginine and sublingual nitroglycerin

    PubMed Central

    Tahvanainen, Anna; Leskinen, Miia; Koskela, Jenni; Ilveskoski, Erkki; Alanko, Juha; Kähönen, Mika; Kööbi, Tiit; Lehtimäki, Lauri; Moilanen, Eeva; Mustonen, Jukka; Pörsti, Ilkka

    2009-01-01

    AIMS To examine the effects of salbutamol and L-arginine, two compounds acting largely on the endothelium, and the endothelium-independent agent nitroglycerin on blood pressure, arterial compliance, cardiac function and vascular resistance. METHODS Continuous radial pulse wave analysis, whole-body impedance cardiography, and plethysmographic blood pressure from fingers in the supine position and during head-up tilt were recorded in nine healthy subjects. Data were captured before and after L-arginine (10 mg mg−1 min−1) or saline infusion, salbutamol (400 µg) or placebo inhalation, and sublingual nitroglycerin (0.25 mg) or placebo resoriblet. RESULTS The results of all measurements were comparable before drug administration. The effects of inhaled salbutamol were apparent in the supine position: systemic vascular resistance (−9.2 ± 2.6%) and augmentation index (−4.0 ± 1.5%) decreased, and heart rate (8.6 ± 2.5%) and cardiac output (8.8 ± 3.1%) increased. L-arginine had no clear effects on supine haemodynamics, but during head-up tilt blood pressure was moderately decreased and reduction in aortic reflection time prevented, indicating improved large arterial compliance. Nitroglycerin reduced supine vascular resistance (−6.7 ± 1.8%) and augmentation index (−7.4 ± 1.6%), and increased cardiac output (+9.2 ± 2.7%). During head-up tilt, nitroglycerin increased cardiac output (+10.6 ± 5.6%) and heart rate (+40 ± 7.5%), decreased vascular resistance (−7.8 ± 5.8%) and augmentation index (−18.7 ± 3.2%), and prevented the decrease in aortic reflection time. CONCLUSIONS Inhaled salbutamol predominantly changed supine haemodynamics, whereas the moderate effects of L-arginine were observed during the head-up tilt. In contrast, small doses of nitroglycerin induced major changes in haemodynamics both supine and during the head-up tilt. Altogether, these results emphasize the importance of haemodynamic measurements in both the supine and upright

  19. Effect of L-arginine on blood pressure in pregnancy-induced hypertension: a randomized placebo-controlled trial.

    PubMed

    Neri, Isabella; Jasonni, Valerio M; Gori, Gian Franco; Blasi, Immacolata; Facchinetti, Fabio

    2006-05-01

    To evaluate the antihypertensive efficacy of L-arginine (L-Arg) repeated infusions in women affected by gestational hypertension. The women were referred to obstetric units in order to assess their clinical conditions and to exclude the presence of severe fetal and/or maternal complications. Inclusion criteria were: maternal age range 16-45 years, diagnosis of gestational hypertension without proteinuria (patients normotensive until the 20th week), and gestational age ranging between 24 and 36 weeks. Each woman was allocated to receive either L-arginine (20 g/500 mL) or placebo treatment through an i.v. line. The infusion was carried out in the morning from 8 a.m. to 10 a.m. and it was repeated for the next four consecutive days. Systolic and diastolic blood pressure values as well as heart rate were recorded with the patient in an upright, seated position at 08:00, 12:00, 16:00 and 20:00 h. Maternal clinical features such as age, height, weight, and gestational age at inclusion were similar between groups. Both systolic and diastolic blood pressures were reduced by treatment, the effect of L-arginine being significantly higher than that of the placebo (systolic values F = 8.59, p < 0.005; diastolic values F = 3.36; p < 0.001). Twenty women assigned to the L-Arg group (32.2%) and 23 to the placebo group (37.7%) were concomitantly treated with antihypertensives before starting the study. Analyzing the subgroup of patients not receiving antihypertensive drugs we found that L-arginine was superior to placebo in lowering systolic (F = 5.42, p < 0.005) and diastolic (F = 2.20, p < 0.005) blood pressure values. In conclusion, these data support the use of L-Arg as an antihypertensive agent for gestational hypertension especially in view of the other beneficial effects nitric oxide donors display in pregnancy. Further, L-Arg seems well tolerated since in this sample none of the patients reported adverse effects requiring study interruption.

  20. Insulin-Increased L-Arginine Transport Requires A2A Adenosine Receptors Activation in Human Umbilical Vein Endothelium

    PubMed Central

    Guzmán-Gutiérrez, Enrique; Westermeier, Francisco; Salomón, Carlos; González, Marcelo; Pardo, Fabián; Leiva, Andrea; Sobrevia, Luis

    2012-01-01

    Adenosine causes vasodilation of human placenta vasculature by increasing the transport of arginine via cationic amino acid transporters 1 (hCAT-1). This process involves the activation of A2A adenosine receptors (A2AAR) in human umbilical vein endothelial cells (HUVECs). Insulin increases hCAT-1 activity and expression in HUVECs, and A2AAR stimulation increases insulin sensitivity in subjects with insulin resistance. However, whether A2AAR plays a role in insulin-mediated increase in L-arginine transport in HUVECs is unknown. To determine this, we first assayed the kinetics of saturable L-arginine transport (1 minute, 37°C) in the absence or presence of nitrobenzylthioinosine (NBTI, 10 µmol/L, adenosine transport inhibitor) and/or adenosine receptors agonist/antagonists. We also determined hCAT-1 protein and mRNA expression levels (Western blots and quantitative PCR), and SLC7A1 (for hCAT-1) reporter promoter activity. Insulin and NBTI increased the extracellular adenosine concentration, the maximal velocity for L-arginine transport without altering the apparent K m for L-arginine transport, hCAT-1 protein and mRNA expression levels, and SLC7A1 transcriptional activity. An A2AAR antagonist ZM-241385 blocked these effects. ZM241385 inhibited SLC7A1 reporter transcriptional activity to the same extent in cells transfected with pGL3-hCAT-1−1606 or pGL3-hCAT-1−650 constructs in the presence of NBTI + insulin. However, SLC7A1 reporter activity was increased by NBTI only in cells transfected with pGL3-hCAT-1−1606, and the ZM-241385 sensitive fraction of the NBTI response was similar in the absence or in the presence of insulin. Thus, insulin modulation of hCAT-1 expression and activity requires functional A2AAR in HUVECs, a mechanism that may be applicable to diseases associated with fetal insulin resistance, such as gestational diabetes. PMID:22844517

  1. Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

    PubMed Central

    Wijnands, Karolina A.P.; Meesters, Dennis M.; van Barneveld, Kevin W.Y.; Visschers, Ruben G.J.; Briedé, Jacob J.; Vandendriessche, Benjamin; van Eijk, Hans M.H.; Bessems, Babs A.F.M.; van den Hoven, Nadine; von Wintersdorff, Christian J.H.; Brouckaert, Peter; Bouvy, Nicole D.; Lamers, Wouter H.; Cauwels, Anje; Poeze, Martijn

    2015-01-01

    Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues. PMID:26132994

  2. R59949, a diacylglycerol kinase inhibitor, inhibits inducible nitric oxide production through decreasing transplasmalemmal L-arginine uptake in vascular smooth muscle cells.

    PubMed

    Shimomura, Tomoko; Nakano, Tomoyuki; Goto, Kaoru; Wakabayashi, Ichiro

    2017-02-01

    Although diacylglycerol kinase (DGK) is known to be expressed in vascular smooth muscle cell, its functional significance remains to be clarified. We hypothesized that DGK is involved in the pathway of cytokine-induced nitric oxide (NO) production in vascular smooth muscle cells. The purpose of this study was to investigate the effects of R59949, a diacylglycerol kinase inhibitor, on inducible nitric oxide production in vascular smooth muscle cell. Cultured rat aortic smooth muscle cells (RASMCs) were used to elucidate the effects of R59949 on basal and interleukin-1β (IL-1β)-induced NO production. The effects of R59949 on protein and mRNA expression of induced nitric oxide synthase (iNOS) and on transplasmalemmal L-arginine uptake were also evaluated using RASMCs. Treatment of RASMCs with R59949 (10 μM) inhibited IL-1β (10 ng/ml)-induced NO production but not basal NO production. Neither protein nor mRNA expression level of iNOS after stimulation with IL-1β was significantly affected by R59949. Estimated enzymatic activities of iNOS in RASMCs were comparable in the absence and presence of R59949. Stimulation of RASMCs with IL-1β caused a marked increase in transplasmalemmal L-arginine uptake into RASMCs. L-Arginine uptake in the presence of IL-1β was markedly inhibited by R59949, while basal L-arginine uptake was not significantly affected by R59949. Both IL-1β-induced NO production and L-arginine uptake were abolished in the presence of cycloheximide (1 μM). The results indicate that R59949 inhibits inducible NO production through decreasing transplasmalemmal L-arginine uptake. DGK is suggested to be involved in cytokine-stimulated L-arginine transport and regulate its intracellular concentration in vascular smooth muscle cell.

  3. L-arginine transport in retinas from streptozotocin diabetic rats: correlation with the level of IL-1 beta and NO synthase activity.

    PubMed

    Carmo, A; Cunha-Vaz, J G; Carvalho, A P; Lopes, M C

    1999-11-01

    Several evidences suggest that the pro-inflammatory cytokines IL-1 beta and the radical NO are implicated as effectors molecules in the pancreatic beta-cells dysfunction; an event preceding the pathogenesis of diabetes. IL-1 beta induces the expression of the inducible isoform of NO synthase (iNOS), which use L-arginine as substrate to overproduce NO. However, it is not known whether these events may participate in the development of diabetic retinopathy, which is the main cause of blindness. In this work, we found an increased level of IL-1 beta in retinas from streptozotocin-induced (STZ) diabetic rats. We also observed that the activity of the NO synthase (NOS) and the L-arginine uptake are enhanced in retinas from STZ-induced diabetic rats as compared to retinas from control rats. We found that the uptake of L-arginine in retinas from control and diabetic rats occurs through a transporter resembling the Y + system, i.e. it is saturable, not affected over the pH range 6.5 to 7.4, and is independent of the extracellular Na+. Nevertheless, the L-arginine transport in retinas from diabetic rats occurs through a carrier with lower affinity (K(m) = 25 microM) and higher capacity (Vmax = 295 +/- 22.4 pmol L-arginine/mg protein) than in retinas from control rats (K(m) = 5 microM and Vmax = 158 +/- 12.8 pmol L-arginine/mg protein) which is correlated with the increased NOS activity and consequent depletion of the intracellular pool of L-arginine.

  4. Synthesis, characterization and anti-microbial activity of pure, Cu2+ and Cd2+ doped organic NLO l-arginine trifluoroacetate single crystals

    NASA Astrophysics Data System (ADS)

    Prasanyaa, T.; Haris, M.; Jayaramakrishnan, V.; Amgalan, M.; Mathivanan, V.

    2013-10-01

    Optically transparent Cu2+ and Cd2+ doped l-arginine trifluoroacetate (LATF) single crystals were grown from its aqueous solution using the slow solvent evaporation technique. The grown crystals were characterized by powder x-ray diffraction to confirm the monoclinic crystal structure. The percentage of transmittance measured using the ultraviolet-visible-near infrared spectrophotometer was found to be more than 80% for doped crystals. The functional group analysis of the grown crystals has been made by Fourier transform infrared spectroscopy. Thermogravimetric/differential thermal analysis was performed for the grown crystals. An atomic absorption study was carried out to determine the presence of Cu2+ and Cd2+. The hardness of the grown crystals was assessed and the results show a significant variation in the hardness value between the pure and doped LATF crystals. The second harmonic generation measurements show that Cu2+ doped LATF is 2.8 times greater and Cd2+ doped is 2.6 times greater than KDP. The anti-bacterial and anti-fungal activities of the title compound were performed using the disc diffusion method against standard bacteria Escherichia coli, Xanthomonas oryzae and against the fungus Aspergillus niger and Aspergillus flavus.

  5. Crystal growth, structural, thermal and mechanical behavior of l-arginine 4-nitrophenolate 4-nitrophenol dihydrate (LAPP) single crystals.

    PubMed

    Mahadevan, M; Ramachandran, K; Anandan, P; Arivanandhan, M; Bhagavannarayana, G; Hayakawa, Y

    2014-12-10

    Single crystals of l-arginine 4-nitrophenolate 4-nitrophenol dihydrate (LAPP) have been grown successfully from the solution of l-arginine and 4-nitrophenol. Slow evaporation of solvent technique was adopted to grow the bulk single crystals. Single crystal X-ray diffraction analysis confirms the grown crystal has monoclinic crystal system with space group of P21. Powder X-ray diffraction analysis shows the good crystalline nature. The crystalline perfection of the grown single crystals was analyzed by HRXRD by employing a multicrystal X-ray diffractometer. The functional groups were identified from proton NMR spectroscopic analysis. Linear and nonlinear optical properties were determined by UV-Vis spectrophotometer and Kurtz powder technique respectively. It is found that the grown crystal has no absorption in the green wavelength region and the SHG efficiency was found to be 2.66 times that of the standard KDP. The Thermal stability of the crystal was found by obtaining TG/DTA curve. The mechanical behavior of the grown crystal has been studied by Vicker's microhardness method. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. A novel nitric oxide-based anticancer therapeutics by macrophage-targeted poly(l-arginine)-based nanoparticles.

    PubMed

    Kudo, Shinpei; Nagasaki, Yukio

    2015-11-10

    In the immune system, macrophages in tumor tissue generate nitric oxide (NO), producing versatile effects including apoptosis of tumor cells, because inducible NO synthase (iNOS) in the cytoplasm of a macrophage produces NO using l-arginine as a substrate. Here, we propose novel NO-triggered immune therapeutics based on our newly designed nanoparticle system. We designed a poly(ethylene glycol)-block-poly(l-arginine) (i.e., PEG-b-P(l-Arg)) block copolymer and prepared polyion complex micelles (PEG-b-P(l-Arg)/m) composed of PEG-b-P(l-Arg) and chondroitin sulfate for systemic anticancer immunotherapy. iNOS treatment of PEG-b-P(l-Arg) did not generate NO, but NO molecules were detected after trypsin pretreatment, indicating that hydrolysis of P(l-Arg) to monomeric arginine was taking place in vitro. RAW264.7 macrophages abundantly generated NO from the PEG-b-P(l-Arg)/m in comparison with control micelles; this finding is indicative of robustness of the proposed method. It is interesting to note that systemic administration of PEG-b-P(l-Arg)/m had no noticeable adverse effects and suppressed the tumor growth rate in C26 tumor-bearing mice in a dose-dependent manner. Our newly designed nanoparticle-assisted arginine delivery system seems to hold promise as an NO-mediated anticancer immunotherapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. [Effects of Nomega-nitro-L-arginine on photoreceptor apoptosis in inherited retinal degeneration of RCS rats].

    PubMed

    Li, Ai-jun; Fang, Jun; Zhu, Xiu-an

    2004-08-18

    To investigate inducible nitric oxide synthase(iNOS) activity of retina and the effects of N(omega)-nitro-L-arginine(N-Arg) on photoreceptor apoptosis in inherited retinal degeneration of Royal College of Surgeons (RCS) rats. iNOS activity was assayed in the whole retinal homogenates of RCS rats and Wistar rats by monitoring the conversion rate of (3)H-arginine to (3)H-citrulline. Intravitreal injection of the NOS inhibitor, N(omega)-nitro-L-arginine(N-Arg), in one lateral eye on postnatal days 17 (P17), P22, P27 and P32 was performed, while the other lateral eye was treated with PBS by intravitreal injection as controls. Then the retinas of the RCS rats were studied by TdT-mediated biotin-dUTP nick-end labeling (TUNEL) for apoptosis on P38. The enzymatic activity of iNOS was elevated in RCS rat retinas on P25. In RCS rats on P38, the percent area of apoptotic photoreceptor nuclei and the thickness of rod and cone layer in the treated group were significantly reduced compared with the controls, while the thickness of outer nuclear layer (ONL) was increased. The inhibitor of NOS might supply a potential medicine for inherited retinal degeneration.

  8. Osteogenic differentiation of immature osteoblasts: Interplay of cell culture media and supplements.

    PubMed

    Brauer, A; Pohlemann, T; Metzger, W

    2016-01-01

    Differentiation of immature osteoblasts to mature osteoblasts in vitro initially was induced by supplementing the medium with β-gylcerophosphate and dexamethasone. Later, ascorbic acid, vitamin D3, vitamin K3 and TGFβ1 were used in varying concentrations as supplements to generate a mature osteoblast phenotype. We tested the effects of several combinations of cell culture media, seeding protocols and osteogenic supplements on osteogenic differentiation of human primary osteoblasts. Osteogenic differentiation was analyzed by staining alkaline phosphatase (ALP) with 5-bromo-4-chloro-3-indolyl-phosphate/nitro blue tetrazolium (BCIP/NBT) and by von Kossa staining of deposited calcium phosphate. The combinations of culture media and supplements significantly influenced osteogenic differentiation, but the seeding protocol did not. Staining of ALP and calcium phosphate could be achieved only if our own mix of osteogenic supplements was used in combination with Dulbecco's modified Eagle medium or if a commercial mix of osteogenic supplements was used in combination with osteoblast growth medium. Especially for von Kossa, we observed great variations in the staining intensity. Because osteogenic differentiation is a complex process, the origin of the osteoblasts, cell culture media and osteogenic supplements should be established by preliminary experiments to achieve optimal differentiation. Staining of ALP or deposited calcium phosphate should be supplemented with qRT-PCR studies to learn more about the influence of specific supplements on osteogenic markers.

  9. L-arginine mediated renaturation enhances yield of human, α6 type IV collagen non-collagenous domain from bacterial inclusion bodies

    PubMed Central

    Gunda, Venugopal; Boosani, Chandra Shekhar; Verma, Raj Kumar; Guda, Chittibabu; Akul Sudhakar, Yakkanti

    2012-01-01

    The anti-angiogenic, carboxy terminal non-collagenous domain (NC1) derived from human Collagen type IV alpha 6 chain, [α6(IV)NC1] or hexastatin, was earlier obtained using different recombinant methods of expression in bacterial systems. However, the effect of L-arginine mediated renaturation in enhancing the relative yields of this protein from bacterial inclusion bodies has not been evaluated. In the present study, direct stirring and on-column renaturation methods using L-arginine and different size exclusion chromatography matrices were applied for enhancing the solubility in purifying the recombinant α6(IV)NC1 from bacterial inclusion bodies. This methodology enabled purification of higher quantities of soluble protein from inclusion bodies, which inhibited endothelial cell proliferation, migration and tube formation. Thus, the scope for L-arginine mediated renaturation in obtaining higher yields of soluble, biologically active NC1 domain from bacterial inclusion bodies was evaluated. PMID:22512648

  10. L-arginine mediated renaturation enhances yield of human, α6 Type IV collagen non-collagenous domain from bacterial inclusion bodies.

    PubMed

    Gunda, Venugopal; Boosani, Chandra Shekhar; Verma, Raj Kumar; Guda, Chittibabu; Sudhakar, Yakkanti Akul

    2012-10-01

    The anti-angiogenic, carboxy terminal non-collagenous domain (NC1) derived from human Collagen type IV alpha 6 chain, [α6(IV)NC1] or hexastatin, was earlier obtained using different recombinant methods of expression in bacterial systems. However, the effect of L-arginine mediated renaturation in enhancing the relative yields of this protein from bacterial inclusion bodies has not been evaluated. In the present study, direct stirring and on-column renaturation methods using L-arginine and different size exclusion chromatography matrices were applied for enhancing the solubility in purifying the recombinant α6(IV)NC1 from bacterial inclusion bodies. This methodology enabled purification of higher quantities of soluble protein from inclusion bodies, which inhibited endothelial cell proliferation, migration and tube formation. Thus, the scope for L-arginine mediated renaturation in obtaining higher yields of soluble, biologically active NC1 domain from bacterial inclusion bodies was evaluated.

  11. Long-term N-acetylcysteine and L-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes.

    PubMed

    Martina, Valentino; Masha, Andi; Gigliardi, Valentina Ramella; Brocato, Loredana; Manzato, Enzo; Berchio, Arrigo; Massarenti, Paola; Settanni, Fabio; Della Casa, Lara; Bergamini, Stefania; Iannone, Anna

    2008-05-01

    Reactive oxygen and nitric oxide (NO) have recently been considered to be involved in the cardiovascular complications of patients with type 2 diabetes, as NO is thought to lose its beneficial physiological effects in the presence of oxygen radicals. For this reason, we tested the effects of l-arginine (ARG) and N-acetylcysteine (NAC) administration in increasing NO bioavailability by reducing free radical formation. A double-blind study was performed on 24 male patients with type 2 diabetes and hypertension divided into two groups of 12 patients that randomly received either an oral supplementation of placebo or NAC + ARG for 6 months. The NAC + ARG treatment caused a reduction of both systolic (P < 0.05) and diastolic (P < 0.05) mean arterial blood pressure, total cholesterol (P < 0.01), LDL cholesterol (P < 0.005), oxidized LDL (P < 0.05), high-sensitive C-reactive protein (P < 0.05), intracellular adhesion molecule (P < 0.05), vascular cell adhesion molecule (P < 0.01), nitrotyrosine (P < 0.01), fibrinogen (P < 0.01), and plasminogen activator inhibitor-1 (P < 0.05), and an improvement of the intima-media thickness during endothelial postischemic vasodilation (P < 0.02). HDL cholesterol increased (P < 0.05). No changes in other parameters studied were observed. NAC + ARG administration seems to be a potential well-tolerated antiatherogenic therapy because it improves endothelial function in hypertensive patients with type 2 diabetes by improving NO bioavailability via reduction of oxidative stress and increase of NO production. Our study's results give prominence to its potential use in primary and secondary cardiovascular prevention in these patients.

  12. The Nitric Oxide Synthase Inhibitor NG-Nitro-L-Arginine Methyl Ester Diminishes the Immunomodulatory Effects of Parental Arginine in Rats with Subacute Peritonitis

    PubMed Central

    Lo, Hui-Chen; Hung, Ching-Yi; Huang, Fu-Huan; Su, Tzu-Cheng; Lee, Chien-Hsing

    2016-01-01

    The combined treatment of parenteral arginine and the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) have been shown to improve liver function and systemic inflammation in subacute peritonitic rats. Here, we investigated the effects of single and combined parenteral arginine and L-NAME treatments on leukocyte and splenocyte immunity. Male Wistar rats were subjected to cecal punctures and were intravenously given total parenteral nutrition solutions with or without arginine and/or L-NAME supplementations for 7 days. Non-surgical and sham-operated rats with no cecal puncture were given a chow diet and parenteral nutrition, respectively. Parenteral feeding elevated the white blood cell numbers and subacute peritonitis augmented the parenteral nutrition-induced alterations in the loss of body weight gain, splenomegaly, and splenocyte decreases. Parenteral arginine significantly increased the B-leukocyte level, decreased the natural killer T (NKT)-leukocyte and splenocyte levels, alleviated the loss in body weight gain and total and cytotoxic T-splenocyte levels, and attenuated the increases in plasma nitrate/nitrite and interferon-gamma production by T-splenocytes. L-NAME infusion significantly decreased NKT-leukocyte level, tumor-necrosis factor (TNF)-alpha production by T-splenocytes and macrophages, and interferon-gamma production by T-leukocytes, monocytes, and T-splenocytes, as well as increased interleukin-6 production by T-leukocytes and monocytes and nitrate/nitrite production by T-leukocytes. Combined treatment significantly decreased plasma nitrate/nitrite, the NKT-leukocyte level, and TNF-alpha production by T-splenocytes. Parenteral arginine may attenuate immune impairment and L-NAME infusion may augment leukocyte proinflammatory response, eliminate splenocyte proinflammatory and T-helper 1 responses, and diminish arginine-induced immunomodulation in combined treatment in subacute peritonitic rats. PMID:27007815

  13. Killing of Leishmania parasites in activated murine macrophages is based on an L-arginine-dependent process that produces nitrogen derivatives

    SciTech Connect

    Maul, J.R.; Ransijn, A.; Buchmueller-Rouiller, Y.

    1991-01-01

    The experiments described in this report were aimed at determining whether L-arginine (L-arg)-derived nitrogen oxidation products (nitric oxide, nitrous acid, nitrites) are involved in the intracellular killing of Leishmania parasites by activated murine macrophages in vitro. Peritoneal or bone marrow-derived macrophages were infected with L. enriettii or L. major, then activated by exposure to recombinant murine interferon-gamma or to macrophage activating factor (MAF)-rich media in the presence of lipopolysaccharide. Activation of macrophages in regular (i.e., arginine-containing) culture medium led to complete destruction of the microorganisms within 24 h (L. enriettii) or 48 h (L. major), concomitant with accumulation of nitritesmore » (NO2-) in the culture fluids. When macrophage activation was carried out in L-arg-free medium, however, neither parasite killing nor NO2- production was obtained. A similar inhibition of macrophage leishmanicidal activity and of NO2- release was observed using media treated with arginase (which converts L-arg to urea and ornithine), or supplemented with NG-monomethyl-L-arg or guanidine (which inhibit the conversion of L-arg to nitrogen oxidation products). In all these situations, an excellent correlation between the levels of NO2- production by macrophages and intracellular killing of Leishmania was observed, whereas no strict correlation was detectable between leishmanicidal activity and superoxide production. Intracellular parasite killing by activated macrophages could be prevented by addition of iron salts to the incubation fluids. Incubation of free parasites with NaNO2 at acid pH led to immobilisation, multiplication arrest, and morphological degeneration of the microorganisms. Similarly, exposure of infected cells to NaNO2 led to killing of the intracellular parasite without affecting macrophage viability.« less

  14. l-Arginine Attenuates Cardiac Dysfunction, But Further Down-Regulates α-Myosin Heavy Chain Expression in Isoproterenol-Induced Cardiomyopathy.

    PubMed

    Kralova, Eva; Doka, Gabriel; Pivackova, Lenka; Srankova, Jasna; Kuracinova, Kristina; Janega, Pavol; Babal, Pavel; Klimas, Jan; Krenek, Peter

    2015-10-01

    In view of previously reported increased capacity for nitric oxide production, we suggested that l-arginine (ARG), the nitric oxide synthase (NOS) substrate, supplementation would improve cardiac function in isoproterenol (ISO)-induced heart failure. Male Wistar rats were treated with ISO for 8 days (5 mg/kg/day, i.p.) or vehicle. ARG was given to control (ARG) and ISO-treated (ISO+ARG) rats in water (0.4 g/kg/day). ISO administration was associated with 40% mortality, ventricular hypertrophy, decreased heart rate, left ventricular dysfunction, fibrosis and ECG signs of ischaemia. RT-PCR showed increased mRNA levels of cardiac hypertrophy marker atrial natriuretic peptide, but not BNP, decreased expression of myosin heavy chain isoform MYH6 and unaltered expression of pathological MYH7. ISO increased the protein levels of endothelial nitric oxide synthase, but at the same time it markedly up-regulated mRNA and protein levels of gp91phox, a catalytical subunit of superoxide-producing NADPH oxidase. Fibrosis was markedly increased by ISO. ARG treatment moderately ameliorated left ventricular dysfunction, but was without effect on cardiac hypertrophy and fibrosis. Combination of ISO and ARG led to a decrease in cav-1 expression, a further increase in MYH7 expression and a down-regulation of MYH6 that inversely correlated with gp91phox mRNA levels. Although ARG, at least partially, improved ISO-impaired basal left ventricular systolic function, it failed to reduce cardiac hypertrophy, fibrosis, oxidative stress and mortality. The protection of contractile performance might be related to increased capacity for nitric oxide production and the up-regulation of MYH7 which may compensate for the marked down-regulation of the major MYH6 isoform. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  15. Early obesity leads to increases in hepatic arginase I and related systemic changes in nitric oxide and L-arginine metabolism in mice.

    PubMed

    Ito, Tatsuo; Kubo, Masayuki; Nagaoka, Kenjiro; Funakubo, Narumi; Setiawan, Heri; Takemoto, Kei; Eguchi, Eri; Fujikura, Yoshihisa; Ogino, Keiki

    2018-02-01

    Obesity is a risk factor for vascular endothelial cell dysfunction characterized by low-grade, chronic inflammation. Increased levels of arginase I and concomitant decreases in L-arginine bioavailability are known to play a role in the pathogenesis of vascular endothelial cell dysfunction. In the present study, we focused on changes in the systemic expression of arginase I as well as L-arginine metabolism in the pre-disease state of early obesity prior to the onset of atherosclerosis. C57BL/6 mice were fed a control diet (CD; 10% fat) or high-fat diet (HFD; 60% fat) for 8 weeks. The mRNA expression of arginase I in the liver, adipose tissue, aorta, and muscle; protein expression of arginase I in the liver and plasma; and systemic levels of L-arginine bioavailability and NO 2 - were assessed. HFD-fed mice showed early obesity without severe disease symptoms. Arginase I mRNA and protein expression levels in the liver were significantly higher in HFD-fed obese mice than in CD-fed mice. Arginase I levels were slightly increased, whereas L-arginine levels were significantly reduced, and these changes were followed by reductions in NO 2 - levels. Furthermore, hepatic arginase I levels positively correlated with plasma arginase I levels and negatively correlated with L-arginine bioavailability in plasma. These results suggested that increases in the expression of hepatic arginase I and reductions in plasma L-arginine and NO 2 - levels might lead to vascular endothelial dysfunction in the pre-disease state of early obesity.

  16. Pharmacokinetic-Pharmacodynamic Model for the Effect of l-Arginine on Endothelial Function in Patients with Moderately Severe Falciparum Malaria

    PubMed Central

    Brussee, Janneke M.; Yeo, Tsin W.; Lampah, Daniel A.; Anstey, Nicholas M.

    2015-01-01

    Impaired organ perfusion in severe falciparum malaria arises from microvascular sequestration of parasitized cells and endothelial dysfunction. Endothelial dysfunction in malaria is secondary to impaired nitric oxide (NO) bioavailability, in part due to decreased plasma concentrations of l-arginine, the substrate for endothelial cell NO synthase. We quantified the time course of the effects of adjunctive l-arginine treatment on endothelial function in 73 patients with moderately severe falciparum malaria derived from previous studies. Three groups of 10 different patients received 3 g, 6 g, or 12 g of l-arginine as a half-hour infusion. The remaining 43 received saline placebo. A pharmacokinetic-pharmacodynamic (PKPD) model was developed to describe the time course of changes in exhaled NO concentrations and reactive hyperemia-peripheral arterial tonometry (RH-PAT) index values describing endothelial function and then used to explore optimal dosing regimens for l-arginine. A PK model describing arginine concentrations in patients with moderately severe malaria was extended with two pharmacodynamic biomeasures, the intermediary biochemical step (NO production) and endothelial function (RH-PAT index). A linear model described the relationship between arginine concentrations and exhaled NO. NO concentrations were linearly related to RH-PAT index. Simulations of dosing schedules using this PKPD model predicted that the time within therapeutic range would increase with increasing arginine dose. However, simulations demonstrated that regimens of continuous infusion over longer periods would prolong the time within the therapeutic range even more. The optimal dosing regimen for l-arginine is likely to be administration schedule dependent. Further studies are necessary to characterize the effects of such continuous infusions of l-arginine on NO and microvascular reactivity in severe malaria. PMID:26482311

  17. Evidence that high-dose L-arginine may be inappropriate for use by diabetic patients as a prophylactic blocker of methylglyoxal glycation.

    PubMed

    Tsai, Chin-Hung; Pan, Tai-Long; Lee, Ying-Shiung; Tai, Yen-Kuang; Liu, Tsan-Zon

    2004-01-01

    Previous reports have suggested that high-dose L-arginine could be used in diabetic patients as a prophylactic blocker for the initial glycation reaction of proteins by methylglyoxal (MG), a reactive dicarbonyl compound of glucose metabolism. Here, we present several lines of evidence to substantiate that this prophylactic intervention may be inappropriate and should be used with care. First, we demonstrated that when various concentrations of L-arginine (2.0-8.0 mM) were added to a fixed concentration of MG (1.56 microM) in a buffered lucigenin solution, dose-dependent generation of superoxide anion (O(-)(2))-mediated ultraweak chemiluminescence (uwCL) occurs. The suppression of uwCL generation by exogenously added superoxide dismutase further substantiated that the interaction between MG and L-arginine generated O(-)(2). This phenomenon can also be demonstrated in a serum-based system. Furthermore, when a fixed concentration of L-arginine (8.0 mM) was added exogenously to a group of sera obtained from either diabetic patients (n = 10) or their matched nondiabetic controls (n = 10), a marked discrepancy in the generation of O(-)(2)-mediated uwCL could be demonstrated (12,534 +/- 3,147 vs. 950 +/- 350 counts; p < 0.001). Taken together, this evidence demonstrates that the appropriateness of using high-dose L-arginine for prophylactic measures in diabetic patients may be questioned, because the inhibition of the glycation reaction between MG and proteins by high-dose L-arginine unexpectedly produces plethoric O(-)(2) as a by-product, which may subsequently aggravate the preexisting oxidative stress status of diabetic patients.

  18. Early energy metabolism-related molecular events in skeletal muscle of diabetic rats: The effects of l-arginine and SOD mimic.

    PubMed

    Stancic, Ana; Filipovic, Milos; Ivanovic-Burmazovic, Ivana; Masovic, Sava; Jankovic, Aleksandra; Otasevic, Vesna; Korac, Aleksandra; Buzadzic, Biljana; Korac, Bato

    2017-06-25

    Considering the vital role of skeletal muscle in control of whole-body metabolism and the severity of long-term diabetic complications, we aimed to reveal the molecular pattern of early diabetes-related skeletal muscle phenotype in terms of energy metabolism, focusing on regulatory mechanisms, and the possibility to improve it using two redox modulators, l-arginine and superoxide dismutase (SOD) mimic. Alloxan-induced diabetic rats (120 mg/kg) were treated with l-arginine or the highly specific SOD mimic, M40403, for 7 days. As appropriate controls, non-diabetic rats received the same treatments. We found that l-arginine and M40403 restored diabetes-induced impairment of phospho-5'-AMP-activated protein kinase α (AMPKα) signaling by upregulating AMPKα protein itself and its downstream effectors, peroxisome proliferator-activated receptor-γ coactivator-1α and nuclear respiratory factor 1. Also, there was a restitution of the protein levels of oxidative phosphorylation components (complex I, complex II and complex IV) and mitofusin 2. Furthermore, l-arginine and M40403 induced translocation of glucose transporter 4 to the membrane and upregulation of protein of phosphofructokinase and acyl coenzyme A dehydrogenase, diminishing negative diabetic effects on limiting factors of glucose and lipid metabolism. Both treatments abolished diabetes-induced downregulation of sarcoplasmic reticulum calcium-ATPase proteins (SERCA 1 and 2). Similar effects of l-arginine and SOD mimic treatments suggest that disturbances in the superoxide/nitric oxide ratio may be responsible for skeletal muscle mitochondrial and metabolic impairment in early diabetes. Our results provide evidence that l-arginine and SOD mimics have potential in preventing and treating metabolic disturbances accompanying this widespread metabolic disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Enhanced expression of endothelial nitric oxide synthase in the myocardium ameliorates the progression of left ventricular hypertrophy in L-arginine treated Wistar-Kyoto rats.

    PubMed

    Ahmad, A; Sattar, M A; Rathore, H A; Abdulla, M H; Khan, S A; Abdullah, N A; Johns, E J

    2016-02-01

    The present study investigated the role of endothelial nitric oxide synthase (eNOS) enzyme in the development of left ventricular hypertrophy (LVH) in Wistar-Kyoto rats. The effect of L-arginine administration on cardiac structure, arterial stiffness, renal and systemic hemodynamic parameters was studied and the change in expression of eNOS and cystathione γ lyase (CSE) in the myocardium of LVH rats was evaluated. LVH was induced using isoprenaline (5 mg/kg, S.C.) and caffeine (62 mg/L in drinking water) for 14 days. Following to that, L-arginine (1.25 g/L in drinking water) was given for 5 weeks as a donor of NO. eNOS and CSE gene expressions were down regulated in the LVH group by about 35% and 67% respectively when compared to control. However, in the LVH group treated with L-arginine there was up regulation of eNOS by almost 27% and down regulation in CSE by 24% when compared to control (all P < 0.05). Heart index and H2S plasma levels were reduced by almost 53% in the L-arginine treated LVH group compared to the control (all P < 0.05). Mean arterial pressure, heart rate and pulse wave velocity were reduced while renal blood perfusion increased in L-arginine treated LVH rats compared to their untreated counterparts (all P < 0.05). The enhanced expression of eNOS in L-arginine treated LVH rats resulted in the amelioration of oxidative and haemodynamic parameters suggesting that NO system is an important therapeutic target in cardiac and LV hypertrophies.

  20. Biallelic expression of the L-arginine:glycine amidinotransferase gene with different methylation status between male and female primordial germ cells in chickens.

    PubMed

    Jang, H J; Lee, M O; Kim, S; Kim, T H; Kim, S K; Song, G; Womack, J E; Han, J Y

    2013-03-01

    The basic functions of DNA methylation include in gene silencing by methylation of specific gene promoters, defense of the host genome from retrovirus, and transcriptional suppression of transgenes. In addition, genomic imprinting, by which certain genes are expressed in a parent-of-origin-specific manner, has been observed in a wide range of plants and animals and has been associated with differential methylation. However, imprinting phenomena of DNA methylation effects have not been revealed in chickens. To analyze whether genomic imprinting occurs in chickens, methyl-DNA immunoprecipitation array analysis was applied across the entire genome of germ cells in early chick embryos. A differentially methylated region (DMR) was detected in the eighth intron of the l-arginine:glycine amidinotransferase (GATM) gene. When the DMR in GATM was analyzed by bisulfite sequencing, the methylation in male primordial germ cells (PGC) of 6-d-old embryos was higher than that in female PGC (57.5 vs. 35.0%). At 8 d, the DMR methylation of GATM in male PGC was 3.7-fold higher than that in female PGC (65.0 vs. 17.5%). Subsequently, to investigate mono- or biallelic expression of the GATM gene during embryo development, we found 2 indel sequences (GTTTAATGC and CAAAAA) within the GATM 3'-untranslated region in Korean Oge (KO) and White Leghorn (WL) chickens. When individual WL and KO chickens were genotyped for indel sequences, 3 allele combinations (homozygous insertion, homozygous deletion, and heterozygotes) were detected in both breeds using a gel shift assay and high-resolution melt assay. The deletion allele was predominant in KO, whereas the insertion allele was predominant in WL. Heterozygous animals were evenly distributed in both breeds (P < 0.01). Despite the different methylation status between male and female PGC, the GATM gene conclusively displayed biallelic expression in PGC as well as somatic embryonic, extraembryonic, and adult chicken tissues.

  1. Electron irradiation induced effects on the physico-chemical properties of L-Arginine Maleate Dihydrate (LAMD) single crystals

    NASA Astrophysics Data System (ADS)

    Thomas, Prince; Dhole, S. D.; Joseph, Ginson P.

    2018-07-01

    Single crystals of L-Arginine Maleate Dihydrate (LAMD) have been synthesized by slow solvent evaporation technique and irradiated with 6 MeV electrons at fluences of 0.5 ×1015e /cm2 , 1.0 ×1015e /cm2 and 1.5 ×1015e /cm2 . The Powder X-ray Diffraction (PXRD) studies showed that the intensity of the diffraction peaks of the Electron Beam (EB) irradiated crystals decreases with irradiation fluence. The electron irradiation induced effects on the optical parameters such as cut-off wavelength, band gap, Urbach energy and refractive index have been studied and the results are tabulated. The electronic parameters such as valence electron plasma energy, ℏωp , Penn gap, Ep , Fermi energy, EF and Electronic polarizability, α for pure and irradiated LAMD crystals are calculated. The electrical and thermal properties of the pure and irradiated LAMD crystals are also investigated.

  2. Atomic force microscopy study on crystal growth of Cu 2+-doped L-arginine phosphate monohydrate crystals

    NASA Astrophysics Data System (ADS)

    Geng, Y. L.; Xu, D.; Wang, Y. L.; Du, W.; Liu, H. Y.; Zhang, G. H.; Wang, X. Q.; Sun, D. L.

    2005-01-01

    Sub-steps and defects of the {1 0 0} planes of Cu 2+-doped L-arginine phosphate monohydrate (LAP) crystals are observed by atomic force microscopy. Formation of sub-steps is not due to the stacking faults but a result of single LAP: Cu 2+ molecule acting as growth unit. Two-dimensional (2D) nuclei with the same height as sub-steps occur on the step-edges. Impurities of Cu 2+ ions cause steps bunch and macrosteps formation. Liquid inclusions in the form of long channels form when the macrosteps lose their stability. Numerous small 3D growth hillocks are found in the channels. The extra stress induced by the 3D islands can result in dislocations and steps mismatches.

  3. Non linear optical studies on semiorganic single crystal: L-arginine 4-nitrophenalate 4-nitrophenol dihydrate (LAPP)

    NASA Astrophysics Data System (ADS)

    Mahadevan, M.; Sankar, P. K.; Vinitha, G.; Arivanandhan, M.; Ramachandran, K.; Anandan, P.

    2017-07-01

    L-arginine 4-nitrophenalate 4-nitrophenol dihydrate (LAPP) has been synthesized and grown by solution growth at room temperature using deionized water as a solvent. The various functional groups of the sample were identified by Fourier transform infra-red and Fourier transforms - Raman spectroscopic analyses. The Laser damage threshold of LAPP has been studied. Refractive index of LAPP single crystal was measured using Metricon prism coupler Instrument. The etching studies were carried out to study the quality of the grown crystals. The third order nonlinear optical properties of LAPP sample was analyzed by the Z-scan technique using 532 nm diode pumped CW Nd: YAG laser. The LAPP material exhibits negative optical nonlinearity. The results show that LAPP sample has potential applications in nonlinear optics and it can be exploited for optical limiting or switching.

  4. Effects of nucleotides adenosine monophosphate and adenosine triphosphate in combination with L-arginine on male rabbit corpus cavernosum tissue.

    PubMed

    Hupertan, V; Neuzillet, Y; Stücker, O; Pons, C; Leammel, E; Lebret, T

    2012-12-01

    Purines and more specifically adenosine monophosphate (AMP) and adenosine triphosphate (ATP) have a strong relaxant effect on smooth muscle cells of the dog, rabbit and human corpus cavernosum, to approximately the same degree as nitric oxide (NO). However, purines are considered as modulators of erectile function rather than key mediators. This suggests that the use of purines combined with NO donors could be effective to treat some specific erectile disorders. The relaxation induced by the combination of l-arginine (Arg), a natural substrate for NO synthase, was assessed with a purine-nucleotide (AMP, ATP) on a rabbit corpus cavernosum model, to determine if these substances could potentiate each other's effect. When a pre-contraction was induced by phenylephrine, AMP alone induced a 43% CC relaxation rate and ATP alone a 26% rate. The relaxation rate induced by Arg was lower in comparison (8% at 5.10(-4) m vs. 25% at AMP 5.10(-4) m and 15% at ATP 5.10(-4) m). NO synthase inhibitor n-nitro-l-arginine did not modify the relaxing effect provoked by AMP suggesting that the mechanism of action of this nucleotide does not involve the NO pathway. The combination of Arg at 5.10(-4) m with either AMP or ATP at different doses ranging from 5.10(-4) to 10(-3) m significantly enhanced the relaxing response reaching rates of 62 and 80% respectively, leading to a synergistic effect. The present data indicate that a 'NO donor' combined with an 'adenosine donor' could be an effective therapeutic approach. © 2012 The Authors. International Journal of Andrology © 2012 European Academy of Andrology.

  5. Protective effect of Mimosa pudica L. in an L-arginine model of acute necrotising pancreatitis in rats.

    PubMed

    Kaur, Jagdeep; Sidhu, Shabir; Chopra, Kanwaljit; Khan, M U

    2016-07-01

    Mimosa pudica is used in traditional medicine for treating various disorders such as inflammatory conditions, diarrhoea, insomnia, alopecia, urogenital infections and wounds. The present study investigated the effect of M. pudica extract (MPE) on L-arginine-induced acute necrotising pancreatitis in rats. The ethanolic extract of M. pudica leaves was studied for the presence of quercetin and gallic acid using high-performance liquid chromatography. Four groups were employed-normal control rats, L-arginine control rats (two intraperitoneal [i.p.] injections of 2 g/kg at an interval of 1 h), MPE-treated rats (400 mg/kg orally) and melatonin-treated rats (positive control 10 mg/kg i.p.), which were further divided into subgroups according to time points (24 h, 3 days and 14 days). Serum amylase, lipase, tumour necrosis factor-α (TNF-α), pancreatic amylase, nucleic acid content, protein, transforming growth factor-β1 (TGF-β1), thiobarbituric reactive substances, glutathione, nitrite/nitrate, collagen content and histopathological examination were carried out. MPE significantly improved acute necrotising pancreatitis by modulating diagnostic markers of pancreatitis such as serum lipase and pancreatic amylase, inflammation (TNF-α), and oxidative and nitrosative stress. Moreover, MPE administration induced regenerative changes in the pancreas evidenced by increased levels of pancreatic proteins, nucleic acid content and histopathology report. In addition, MPE improved TGF-β1 and collagen levels thereby preventing fibrosis. The current investigation indicates the novel role of MPE in reducing the severity of acute necrotising pancreatitis by plausible mechanisms such as anti-inflammatory and anti-fibrotic activity and by promoting repair and regeneration of the pancreas.

  6. Activation of l-arginine transport by protein kinase C in rabbit, rat and mouse alveolar macrophages

    PubMed Central

    Racké, Kurt; Hey, Claudia; Mössner, Jutta; Hammermann, Rainer; Stichnote, Christina; Wessler, Ignaz

    1998-01-01

    The role of protein kinase C in controlling L-arginine transport in alveolar macrophages was investigated. L-[3H]Arginine uptake in rabbit alveolar macrophages declined by 80 % after 20 h in culture. 4β-Phorbol 12-myristate 13-acetate (PMA), but not 4α-phorbol 12-myristate 13-acetate (α-PMA), present during 20 h culture, enhanced L-[3H]arginine uptake more than 10-fold. Staurosporine and chelerythrine opposed this effect. L-[3H]Arginine uptake was saturable and blockable by L-lysine. After PMA treatment Vmax was increased more than 5-fold and Km was reduced from 0.65 to 0.32 mM. Time course experiments showed that PMA increased L-[3H]arginine uptake almost maximally within 2 h. This short-term effect was not affected by cycloheximide or actinomycin D. L-[3H]Arginine uptake and its stimulation by PMA was also observed in sodium-free medium. L-Leucine (0.1 mM) inhibited L-[3H]arginine uptake by 50 % in sodium-containing medium, but not in sodium-free medium. At 1 mM, L-leucine caused significant inhibition in sodium-free medium also. L-Leucine showed similar effects on PMA-treated cells. N-Ethylmaleimide (200 μm, 10 min) reduced L-[3H]arginine uptake by 70 % in control cells, but had no effect on PMA-treated (20 or 2 h) cells. In alveolar macrophages, multiple transport systems are involved in L-arginine uptake, which is markedly stimulated by protein kinase C, probably by modulation of the activity of already expressed cationic amino acid transporters. PMID:9714862

  7. Analysis of physicochemical properties of ternary systems of oxaprozin with randomly methylated-ß-cyclodextrin and l-arginine aimed to improve the drug solubility.

    PubMed

    Mennini, Natascia; Maestrelli, Francesca; Cirri, Marzia; Mura, Paola

    2016-09-10

    The influence of l-arginine on the complexing and solubilizing power of randomly-methylated-β-cyclodextrin (RameβCD) towards oxaprozin, a very poorly soluble anti-inflammatory drug, was examined. The interactions between the components were investigated both in solution, by phase-solubility analysis, and in the solid state, by differential scanning calorimetry, FTIR and X-ray powder diffractometry. The morphology of the solid products was examined by Scanning Electron Microscopy. Results of phase-solubility studies indicated that addition of arginine enhanced the RameβCD complexing and solubilizing power of about 3.0 and 4.5 times, respectively, in comparison with the binary complex (both at pH≈6.8). The effect of arginine was not simply additive, but synergistic, being the ternary system solubility higher than the sum of those of the respective drug-CD and drug-arginine binary systems. Solid equimolar ternary systems were prepared by physical mixing, co-grinding, coevaporation and kneading techniques, to explore the effect of the preparation method on the physicochemical properties of the final products. The ternary co-ground product exhibited a dramatic increase in both drug dissolution efficiency and percent dissolved at 60min, whose values (83.6 and 97.1, respectively) were about 3 times higher than the sum of those given by the respective drug-CD and drug-aminoacid binary systems. Therefore, the ternary co-ground system with arginine and RameβCD appears as a very valuable product for the development of new more effective delivery systems of oxaprozin, with improved safety and bioavailability. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Protective effect of chlorogenic acid on the inflammatory damage of pancreas and lung in mice with l-arginine-induced pancreatitis.

    PubMed

    Ohkawara, Tatsuya; Takeda, Hiroshi; Nishihira, Jun

    2017-12-01

    Pancreatitis is characterized by inflammatory disease with severe tissue injury in pancreas, and the incidence of pancreatitis has been recently increasing. Although several treatments of acute pancreatitis have been developed, some patients have been resistant to current therapy. Chlorogenic acid (CGA) is one of the polyphenols, and is known to have an anti-inflammatory effect. In this study, we investigated the effects of CGA on experimental pancreatitis in mice. Pancreatitis was induced by twice injection of l-arginine (5g/kg body weight). Mice were intraperitoneally injected with CGA (20mg/kg or 40mg/kg) 1h before administration of l-arginine. Administration of 40mg/kg of CGA decreased the histological severity of pancreatitis and pancreatitis-associated lung injury. Moreover, administration of CGA inhibited the levels of pancreatic enzyme activity. Interestingly, CGA reduced the serum and pancreatic levels of macrophage migration inhibitory factor (MIF) in mice with l-arginine-induced pancreatitis. Our results suggest that CGA has an anti-inflammatory effect on l-arginine-induced pancreatitis and pancreatitis-associated lung injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Local antinociceptive action of fluoxetine in the rat formalin assay: role of l-arginine/nitric oxide/cGMP/KATP channel pathway.

    PubMed

    Ghorbanzadeh, Behnam; Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Alboghobeish, Soheila

    2018-02-01

    The present study was conducted to evaluate the local antinociceptive actions of fluoxetine, a selective serotonin reuptake inhibitor, and the possible involvement of the l-arginine/NO/cGMP/K ATP channel pathway in this effect using the formalin test in rats. To elucidate the underlying mechanisms, animals were pre-treated with l-NAME, aminoguanidine, methylene blue, glibenclamide, l-arginine, sodium nitroprusside, or diazoxide. Local ipsilateral, but not contralateral, administration of fluoxetine (10-300 μg/paw) dose-dependently suppressed flinching number during both early and late phases of the test, and this was comparable with morphine also given peripherally. Pre-treatment with l-NAME, aminoguanidine, methylene blue, or glibenclamide dose-dependently prevented fluoxetine (100 μg/paw)-induced antinociception in the late phase. In contrast, administration of l-arginine, sodium nitroprusside, and diazoxide significantly enhanced the antinociception caused by fluoxetine in the late phase of the test. However, these treatments had no significant effect on the antinociceptive response of fluoxetine in the early phase of the formalin test. Our data demonstrate that local peripheral antinociception of fluoxetine during the late phase of the formalin test could be due to activation of l-arginine/NO/cGMP/K ATP channel pathway. The peripheral action of fluoxetine raises the possibility that topical application of this drug (e.g., as a cream, ointment, or jelly) may be a useful method for relieving the inflammatory pain states.

  10. Insights into the molecular basis for substrate binding and specificity of the wild-type L-arginine/agmatine antiporter AdiC.

    PubMed

    Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Gapsys, Vytautas; Ucurum, Zöhre; de Groot, Bert L; Fotiadis, Dimitrios

    2016-09-13

    Pathogenic enterobacteria need to survive the extreme acidity of the stomach to successfully colonize the human gut. Enteric bacteria circumvent the gastric acid barrier by activating extreme acid-resistance responses, such as the arginine-dependent acid resistance system. In this response, l-arginine is decarboxylated to agmatine, thereby consuming one proton from the cytoplasm. In Escherichia coli, the l-arginine/agmatine antiporter AdiC facilitates the export of agmatine in exchange of l-arginine, thus providing substrates for further removal of protons from the cytoplasm and balancing the intracellular pH. We have solved the crystal structures of wild-type AdiC in the presence and absence of the substrate agmatine at 2.6-Å and 2.2-Å resolution, respectively. The high-resolution structures made possible the identification of crucial water molecules in the substrate-binding sites, unveiling their functional roles for agmatine release and structure stabilization, which was further corroborated by molecular dynamics simulations. Structural analysis combined with site-directed mutagenesis and the scintillation proximity radioligand binding assay improved our understanding of substrate binding and specificity of the wild-type l-arginine/agmatine antiporter AdiC. Finally, we present a potential mechanism for conformational changes of the AdiC transport cycle involved in the release of agmatine into the periplasmic space of E. coli.

  11. Novel photoluminescence enzyme immunoassay based on supramolecular host-guest recognition using L-arginine/6-aza-2-thiothymine-stabilized gold nanocluster.

    PubMed

    Wang, Youmei; Lu, Minghua; Tang, Dianping

    2018-06-30

    A new photoluminescence (PL) enzyme immunoassay was designed for sensitive detection of aflatoxin B 1 (AFB 1 ) via an innovative enzyme substrate, 6-aza-2-thiothymine-stabilized gold nanocluster (AAT-AuNC) with L-arginine. The enzyme substrate with strong PL intensity was formed through supramolecular host-guest assembly between guanidine group of L-arginine and AAT capped on the surface of AuNC. Upon arginase introduction, the captured L-arginine was hydrolyzed into ornithine and urea, thus resulting in the decreasing PL intensity. Based on this principle, a novel competitive-type immunoreaction was first carried out on AFB 1 -bovine serum albumin (AFB 1 -BSA) conjugate-coated microplate, using arginase-labeled anti-AFB 1 antibody as the competitor. Under the optimum conditions, the PL intensity increased with the increment of target AFB 1 , and allowed the detection of the analyte at concentrations as low as 3.2 pg mL -1 (ppt). Moreover, L-arginine-AAT-AuNC-based PL enzyme immunoassay afforded good reproducibility and acceptable specificity. In addition, the accuracy of this methodology, referring to commercial AFB 1 ELISA kit, was evaluated to analyze naturally contaminated or spiked peanut samples, giving well-matched results between two methods, thus representing a useful scheme for practical application in quantitative monitoring of mycotoxins in foodstuff. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Structure of the C-terminal effector-binding domain of AhrC bound to its corepressor l-arginine

    SciTech Connect

    Garnett, James A.; Baumberg, Simon; Stockley, Peter G.

    2007-11-01

    The crystal structure of the C-terminal domain hexameric core of AhrC, with bound corepressor (l-arginine), has been solved at 1.95 Å resolution. Binding of l-arginine results in a rotation between the two trimers of the hexamer, leading to the activation of the DNA-binding state. The arginine repressor/activator protein (AhrC) from Bacillus subtilis belongs to a large family of multifunctional transcription factors that are involved in the regulation of bacterial arginine metabolism. AhrC interacts with operator sites in the promoters of arginine biosynthetic and catabolic operons, acting as a transcriptional repressor at biosynthetic sites and an activator of transcription at catabolicmore » sites. AhrC is a hexamer of identical subunits, each having two domains. The C-terminal domains form the core of the protein and are involved in oligomerization and l-arginine binding. The N-terminal domains lie on the outside of the compact core and play a role in binding to 18 bp DNA operators called ARG boxes. The C-terminal domain of AhrC has been expressed, purified and characterized, and also crystallized as a hexamer with the bound corepressor l-arginine. Here, the crystal structure refined to 1.95 Å is presented.« less

  13. Reengineering of the feedback-inhibition enzyme N-acetyl-L-glutamate kinase to enhance L-arginine production in Corynebacterium crenatum.

    PubMed

    Zhang, Jingjing; Xu, Meijuan; Ge, Xiaoxun; Zhang, Xian; Yang, Taowei; Xu, Zhenghong; Rao, Zhiming

    2017-02-01

    N-acetyl-L-glutamate kinase (NAGK) catalyzes the second step of L-arginine biosynthesis and is inhibited by L-arginine in Corynebacterium crenatum. To ascertain the basis for the arginine sensitivity of CcNAGK, residue E19 which located at the entrance of the Arginine-ring was subjected to site-saturated mutagenesis and we successfully illustrated the inhibition-resistant mechanism. Typically, the E19Y mutant displayed the greatest deregulation of L-arginine feedback inhibition. An equally important strategy is to improve the catalytic activity and thermostability of CcNAGK. For further strain improvement, we used site-directed mutagenesis to identify mutations that improve CcNAGK. Results identified variants I74V, F91H and K234T display higher specific activity and thermostability. The L-arginine yield and productivity of the recombinant strain C. crenatum SYPA-EH3 (which possesses a combination of all four mutant sites, E19Y/I74V/F91H/K234T) reached 61.2 and 0.638 g/L/h, respectively, after 96 h in 5 L bioreactor fermentation, an increase of approximately 41.8% compared with the initial strain.

  14. Spontaneous, L-arginine-induced and spironolactone-induced regression of protein remodeling of the left ventricle in L-NAME-induced hypertension.

    PubMed

    Simko, F; Potácová, A; Pelouch, V; Paulis, L; Matúsková, J; Krajcírovicová, K; Pechánová, O; Adamcová, M

    2007-01-01

    N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension is associated with protein remodeling of the left ventricle. The aim of the study was to show, whether aldosterone receptor blocker spironolactone and precursor of NO-production L-arginine were able to reverse the protein rebuilding of the left ventricle. Six groups of male Wistar rats were investigated: control 4 (4 weeks placebo), L-NAME (4 weeks L-NAME), spontaneous-regression (4 weeks L-NAME + 3 weeks placebo), spironolactone-regression (4 weeks L-NAME + 3 weeks spironolactone), L-arginine-regression (4 weeks L-NAME + 3 weeks arginine), control 7 (7 weeks placebo). L-NAME administration induced hypertension, hypertrophy of the left ventricle (LV), and the increase of metabolic and contractile as well as soluble and insoluble collagenous protein concentration. The systolic blood pressure and relative weight of the LV decreased in all three groups with regression, while the most prominent attenuation of the LVH was observed after spironolactone treatment. In the spontaneous-regression and L-arginine-regression groups the concentrations of individual proteins were not significantly different from the control value. However, in the spironolactone-regression group the concentration of metabolic, contractile and insoluble collagenous proteins remained significantly increased in comparison with the control group. The persistence of the increased protein concentration in the spironolactone group may be related to the more prominent reduction of myocardial water content by spironolactone.

  15. Progesterone up-regulates vasodilator effects of calcitonin gene-related peptide in N(G)-nitro-L-arginine methyl ester-induced hypertension.

    PubMed

    Gangula, P R; Wimalawansa, S J; Yallampalli, C

    1997-04-01

    We recently reported that calcitonin gene-related peptide can reverse the hypertension produced by N(G)-nitro-L-arginine methyl ester in pregnant rats. In the current study we investigated whether these vasodilator effects of calcitonin gene-related peptide were progesterone dependent. Calcitonin gene-related peptide or N(G)-nitro-L-arginine methyl ester was infused through osmotic minipumps, either separately or in combination, to groups of five pregnant rats from day 17 of gestation until day 8 post partum or to nonpregnant ovariectomized rats for 8 days. Progesterone was injected during days 1 to 6 post partum and for 6 days after ovariectomy. Systolic blood pressure was measured daily. Animals receiving N(G)-nitro-L-arginine methyl ester exhibited significant elevations of blood pressure during pregnancy and post partum. Coadministration of calcitonin gene-related peptide to these rats reversed the hypertension during pregnancy but not during the postpartum period. At the dose used in this study calcitonin gene-related peptide administered alone was without significant effects on blood pressure. However, it reduced both the mortality and growth restriction of the fetus associated with N(G)-nitro-L-arginine methyl ester in these animals. Calcitonin gene-related peptide reversed the hypertension in N(G)-nitro-L-arginine methyl ester-infused postpartum rats during the periods of progesterone treatment only, and these effects were lost when progesterone treatment was stopped. Neither progesterone nor calcitonin gene-related peptide alone were effective. To further confirm these observations, progesterone effects were tested in ovariectomized adult rats. Similar to the findings in postpartum rats, calcitonin gene-related peptide completely reversed the elevation in blood pressure in N(G)-nitro-L-arginine methyl ester-treated rats receiving progesterone injections. The effects of calcitonin gene-related peptide were apparent only during the progesterone treatment

  16. Inhibition of arginase in rat and rabbit alveolar macrophages by Nω-hydroxy-D,L-indospicine, effects on L-arginine utilization by nitric oxide synthase

    PubMed Central

    Hey, Claudia; Boucher, Jean-Luc; Vadon-Le Goff, Sandrine; Ketterer, Gabi; Wessler, Ignaz; Racké, Kurt

    1997-01-01

    Alveolar macrophages (AMΦ) exhibit arginase activity and may, in addition, express an inducible form of nitric oxide (NO) synthase (iNOS). Both pathways may compete for the substrate, L-arginine. The present study tested whether two recently described potent inhibitors of liver arginase (Nω-hydroxy-D,L-indospicine and 4-hydroxyamidino-D,L-phenylalanine) might also inhibit arginase in AMΦ and whether inhibition of arginase might affect L-arginine utilization by iNOS. AMΦ obtained by broncho-alveolar lavage of rat and rabbit isolated lungs were disseminated (2.5 or 3×106 cells per well) and allowed to adhere for 2 h. Thereafter, they were either used to study [*H]-L-arginine uptake (37 kBq, 0.1 μM, 2 min) or cultured for 20 h in the absence or presence of bacterial lipopolysaccharide (LPS). Cultured AMΦ were incubated for 1 h with [*H]-L-arginine (37 kBq, 0.1 μM) and the accumulation of [*H]-L-citrulline (NOS activity) and [*H]-L-ornithine (arginase activity) was determined. During 1 h incubation of rabbit AMΦ with [*H]-L-arginine, no [*H]-L-citrulline, but significant amounts of [*H]-L-ornithine (150 d.p.m.×1000) were formed. Nω-hydroxy-D,L-indospicine and 4-hydroxyamidino-D,L-phenylalanine, present during incubation, concentration-dependently reduced [*H]-L-ornithine formation (IC50: 2 and 45 μM, respectively). Nω-hydroxy-D,L-indospicine (up to 100 μM) had no effect on [*H]-L-arginine uptake into rabbit AMΦ, whereas 4-hydroxyamidino-D,L-phenylalanine caused a concentration-dependent inhibition (IC50: 300 μM). Rat AMΦ, cultured in the absence of LPS, formed significant amounts of [*H]-L-citrulline and [*H]-L-ornithine (133 and 212 d.p.m.×1000, respectively) when incubated for 1 h with [*H]-L-arginine. When AMΦ had been cultured in the presence of 0.1 or 1 μg ml−1 LPS, the formation of [*H]-L-citrulline was enhanced by 37±8.3 and 99±12% and that of [*H]-L-ornithine reduced by 21±8.7 and 70±2.5%, respectively

  17. NO system dependence of atropine-induced mydriasis and L-NAME- and L-arginine-induced miosis: Reversal by the pentadecapeptide BPC 157 in rats and guinea pigs.

    PubMed

    Kokot, Antonio; Zlatar, Mirna; Stupnisek, Mirjana; Drmic, Domagoj; Radic, Radivoje; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

    2016-01-15

    We revealed an immediate and hours-lasting particular NO-specific parallel miotic effect of L-NAME and L-arginine in rats and guinea pigs and a stable gastric pentadecapeptide BPC 157 157-particular effect vs. that of atropine-induced mydriasis while examining the NO system role in the normal pupils responses and pupils with atropine-induced mydriasis. We also assessed the responses to BPC 157 and its possible modulation of the changes caused by L-NAME/L-arginine and atropine. We administered locally (two drops/eye) or systemically (intraperitoneally/kg) [BPC 157 (0.4µg/eye; 10µg, 10ng, 10pg/kg), L-NAME (0.1mg/eye; 5mg/kg), and L-arginine (2mg/eye; 100mg/kg) alone and combined] at 3min prior to assessment (normal pupils) or alternatively at maximal 1% atropine-induced mydriasis (30min after two drops were administered to each eye). L-NAME/L-arginine. Normal pupil. L-NAME-miosis and L-arginine-miosis shortened and attenuated each other's responses when combined (L-NAME+L-arginine) (except with guinea pigs treated locally) and were thereby NO-specific. Atropine-pupil. Both L-NAME and L-arginine counteracted atropine-induced mydriasis. With few exceptions, the atropine+L-NAME+L-arginine-animals showed a consistent shift toward the left. BPC 157. Normal pupil. Always, BPC 157 alone (both species; locally; systemically; all regimens) did not affect normal pupils. Despite specific exceptions, BPC 157 distinctively affects L-arginine-miosis (prolongation) and L-NAME-miosis (shortening). When L-arginine and L-NAME were combined (L-NAME+L-arginine+BPC 157), the effect was less pronounced. Atropine-pupil. BPC 157 alone counteracted atropine-induced mydriasis. With few exceptions (when administered with L-NAME or L-arginine or L-NAME+L-arginine), BPC 157 augments their counteracting effects. Thus, along with its l-NAME/L-arginine effects, BPC 157 participates in ocular control, potentially via NO-mediated and cholinergic mechanisms. Copyright © 2015 Elsevier B.V. All

  18. Role of adenosine transport in gestational diabetes-induced l-arginine transport and nitric oxide synthesis in human umbilical vein endothelium

    PubMed Central

    Vásquez, Gustavo; Sanhueza, Felipe; Vásquez, Rodrigo; González, Marcelo; Martín, Rody San; Casanello, Paola; Sobrevia, Luis

    2004-01-01

    Gestational diabetes is associated with increased l-arginine transport and nitric oxide (NO) synthesis, and reduced adenosine transport in human umbilical vein endothelial cells (HUVEC). Adenosine increases endothelial l-arginine/NO pathway via A2 purinoceptors in HUVEC from normal pregnancies. It is unknown whether the effect of gestational diabetes is associated with activation of these purinoceptors or altered expression of human cationic amino acid transporter 1 (hCAT-1) or human equilibrative nucleoside transporter 1 (hENT1), or endothelial NO synthase (eNOS) in HUVEC. Cells were isolated from normal or gestational diabetic pregnancies and cultured up to passage 2. Gestational diabetes increased hCAT-1 mRNA expression (2.4-fold) and activity, eNOS mRNA (2.3-fold), protein level (2.1-fold), and phosphorylation (3.8-fold), but reduced hENT1 mRNA expression (32%) and activity. Gestational diabetes increased extracellular adenosine (2.7 μm), and intracellular l-arginine (1.9 mm) and l-citrulline (0.7 mm) levels compared with normal cells (0.05 μm, 0.89 mm, 0.35 mm, respectively). Incubation of HUVEC from normal pregnancies with 1 μm nitrobenzylthioinosine (NBMPR) mimicked the effect of gestational diabetes, but NBMPR was ineffective in diabetic cells. Gestational diabetes and NBMPR effects involved eNOS, PKC and p42/44mapk activation, and were blocked by the A2a purinoceptor antagonist ZM-241385. Thus, gestational diabetes increases the l-arginine/NO pathway involving activation of mitogen-activated protein (MAP) kinases, protein kinase C (PKC) and NO cell signalling cascades following activation of A2a purinoceptors by extracellular adenosine. A functional relationship is proposed between adenosine transport and modulation of l-arginine transport and NO synthesis in HUVEC, which could be determinant in regulating vascular reactivity in diabetes mellitus. PMID:15272035

  19. Agmatine enhances the anticonvulsant effect of lithium chloride on pentylenetetrazole-induced seizures in mice: Involvement of L-arginine/nitric oxide pathway.

    PubMed

    Bahremand, Arash; Ziai, Pouya; Khodadad, Tina Kabiri; Payandemehr, Borna; Rahimian, Reza; Ghasemi, Abbas; Ghasemi, Mehdi; Hedayat, Tina; Dehpour, Ahmad Reza

    2010-07-01

    After nearly 60years, lithium is still the mainstay in the treatment of mood disorders. In addition to its antimanic and antidepressant effects, lithium also has anticonvulsant properties. Similar to lithium, agmatine plays a protective role in the central nervous system against seizures and has been reported to enhance the effect of different antiepileptic agents. Moreover, both agmatine and lithium have modulatory effects on the L-arginine/nitric oxide pathway. This study was designed to investigate: (1) whether agmatine and lithium exert a synergistic effect against clonic seizures induced by pentylenetetrazole and (2) whether or not this synergistic effect is mediated through inhibition of the L-arginine/nitric oxide pathway. In our study, acute administration of a single potent dose of lithium chloride (30mg/kg ip) increased seizure threshold, whereas pretreatment with a low and independently noneffective dose of agmatine (3mg/kg) potentiated a subeffective dose of lithium (10mg/kg). N(G)-L-arginine methyl ester (L-NAME, nonspecific nitric oxide synthase inhibitor) at 1 and 5mg/kg and 7-nitroindazole (7-NI, preferential neuronal nitric oxide synthase inhibitor) at 15 and 30mg/kg augmented the anticonvulsant effect of the noneffective combination of lithium (10mg/kg ip) and agmatine (1mg/kg), whereas several doses (20 and 40mg/kg) of aminoguanidine (inducible nitric oxide synthase inhibitor) failed to alter the seizure threshold of the same combination. Furthermore, pretreatment with independently noneffective doses (30 and 60mg/kg) of L-arginine (substrate for nitric oxide synthase) inhibited the potentiating effect of agmatine (3mg/kg) on lithium (10mg/kg). Our findings demonstrate that agmatine and lithium chloride have synergistic anticonvulsant properties that may be mediated through the L-arginine/nitric oxide pathway. In addition, the role of constitutive nitric oxide synthase versus inducible nitric oxide synthase is prominent in this phenomenon

  20. Combining glial cell line-derived neurotrophic factor gene delivery (AdGDNF) with L-arginine decreases contusion size but not behavioral deficits after traumatic brain injury.

    PubMed

    Degeorge, M L; Marlowe, D; Werner, E; Soderstrom, K E; Stock, M; Mueller, A; Bohn, M C; Kozlowski, D A

    2011-07-27

    Our laboratory has previously demonstrated that viral administration of glial cell line-derived neurotrophic factor (AdGDNF), one week prior to a controlled cortical impact (CCI) over the forelimb sensorimotor cortex of the rat (FL-SMC) is neuroprotective, but does not significantly enhance recovery of sensorimotor function. One possible explanation for this discrepancy is that although protected, neurons may not have been functional due to enduring metabolic deficiencies. Additionally, metabolic events following TBI may interfere with expression of therapeutic proteins administered to the injured brain via gene therapy. The current study focused on enhancing the metabolic function of the brain by increasing cerebral blood flow (CBF) with l-arginine in conjunction with administration of AdGDNF immediately following CCI. An adenoviral vector harboring human GDNF was injected unilaterally into FL-SMC of the rat immediately following a unilateral CCI over the FL-SMC. Within 30min of the CCI and AdGDNF injections, some animals were injected with l-arginine (i.v.). Tests of forelimb function and asymmetry were administered for 4weeks post-injury. Animals were sacrificed and contusion size and GDNF protein expression measured. This study demonstrated that rats treated with AdGDNF and l-arginine post-CCI had a significantly smaller contusion than injured rats who did not receive any treatment, or injured rats treated with either AdGDNF or l-arginine alone. Nevertheless, no amelioration of behavioral deficits was seen. These findings suggest that AdGDNF alone following a CCI was not therapeutic and although combining it with l-arginine decreased contusion size, it did not enhance behavioral recovery. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Regression of left ventricular hypertrophy and aortic remodelling in NO-deficient hypertensive rats: effect of L-arginine and spironolactone.

    PubMed

    Paulis, L; Matuskova, J; Adamcova, M; Pelouch, V; Simko, J; Krajcirovicova, K; Potacova, A; Hulin, I; Janega, P; Pechanova, O; Simko, F

    2008-09-01

    We investigated, whether the substrate for nitric oxide (NO) formation -L-arginine - and the aldosterone receptor antagonist - spironolactone - are able to reverse alterations of the left ventricle (LV) and aorta in N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Six groups of male adult Wistar rats were investigated: controls after 4 and 7 weeks of experiment, rats treated with L-NAME for 4 weeks and three recovery groups: spontaneous-reversion (4 weeks L-NAME + 3 weeks placebo), spironolactone-induced reversion (4 weeks L-NAME + 3 weeks spironolactone) and L-arginine-induced reversion (4 weeks L-NAME+ 3 weeks L-arginine). Blood pressure was measured by tail-cuff plethysmography. Relative weight of the LV, myocardial fibrosis (based upon histomorphometry and hydroxyproline determination) and conjugated dienes in the LV and aortic cross-sectional area, inner diameter and wall thickness were determined. NO-synthase activity was investigated in the LV and aorta. L-NAME administration induced hypertension, left ventricular hypertrophy (LVH), LV fibrosis, aortic thickening and diminution of NO-synthase activity in the LV and aorta. Reduction in blood pressure and regression of LVH were observed in all recovery groups, yet reduction in LV fibrosis and aortic thickening were not. NO-synthase activity was restored only in the L-arginine and spironolactone group. In our study, the reversion of hypertension and LVH was not dependent on the restoration of NO-synthase activity. Moreover, LV fibrosis and aortic remodelling seem to be more resistant to conditions resulting in regression of LVH. Preserved level of fibrosis in the initial period of LVH regression might result in loss of structural homogeneity and possible functional alterations of the LV.

  2. Venlafaxine prevents morphine antinociceptive tolerance: The role of neuroinflammation and the l-arginine-nitric oxide pathway.

    PubMed

    Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Ghorbanzadeh, Behnam; Alboghobeish, Soheila; Amirgholami, Neda; Houshmand, Gholamreza; Cauli, Omar

    2018-05-01

    Opioid-induced neuroinflammation and the nitric oxide (NO) signal-transduction pathway are involved in the development of opioid analgesic tolerance. The antidepressant venlafaxine (VLF) modulates NO in nervous tissues, and so we investigated its effect on induced tolerance to morphine, neuroinflammation, and oxidative stress in mice. Tolerance to the analgesic effects of morphine were induced by injecting mice with morphine (50 mg/kg) once a day for three consecutive days; the effect of co-administration of VLF (5 or 40 mg/kg) with morphine was similarly tested in a separate group. To determine if the NO precursor l-arginine hydrochloride (l-arg) or NO are involved in the effects rendered by VLF, animals were pre-treated with l-arg (200 mg/kg), or the NO synthesis inhibitors N(ω)-nitro-l-arginine methyl ester (L-NAME; 30 mg/kg) or aminoguanidine hydrochloride (AG; 100 mg/kg), along with VLF (40 mg/kg) for three days before receiving morphine for another three days. Nociception was assessed with a hot-plate test on the fourth day, and the concentration of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6), interleukin-10, brain-derived neurotrophic factor, NO, and oxidative stress factors such as total thiol, malondialdehyde content, and glutathione peroxidase (GPx) activity in the brain was also determined. Co-administration of VLF with morphine attenuated morphine-induced analgesic tolerance and prevented the upregulation of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), NO, and malondialdehyde in brains of mice with induced morphine tolerance; chronic VLF administration inhibited this decrease in brain-derived neurotrophic factor, total thiol, and GPx levels. Moreover, repeated administration of l-arg before receipt of VLF antagonized the effects induced by VLF, while L-NAME and AG potentiated these effects. VLF attenuates morphine-induced analgesic tolerance, at least partly because of its anti

  3. A mechanism enhancing macromolecule transport through paracellular spaces induced by Poly-L-Arginine: Poly-L-Arginine induces the internalization of tight junction proteins via clathrin-mediated endocytosis.

    PubMed

    Yamaki, Tsutomu; Kamiya, Yusuke; Ohtake, Kazuo; Uchida, Masaki; Seki, Toshinobu; Ueda, Hideo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

    2014-09-01

    Poly-L-arginine (PLA) enhances the paracellular permeability of the Caco-2 cell monolayer to hydrophilic macromolecules by disappearance of tight junction (TJ) proteins from cell-cell junctions. However, the mechanism of the disappearance of TJ proteins in response to PLA has been unclear. In this study, we investigated the mechanism of disappearance of TJ proteins from cell-cell junctions after the application of PLA to Caco-2 cell monolayers. The membrane conductance (Gt), FITC-dextran (FD-4) permeability, and localization of TJ proteins were examined after the treatment of Caco-2 cell monolayers with PLA in the presence of various endocytosis inhibitors. In addition, the localization of endosome marker proteins was also observed. Clathrin-mediated endocytosis inhibitors suppressed the increase in Gt and Papp of FD-4 induced by PLA, and also significantly suppressed the disappearance of TJ proteins induced by PLA. Furthermore, occludin, one of the TJ proteins, colocalized with early endosome and recycling endosomes after the internalization of occludin induced by PLA, and then was recycled to the cell-cell junctions. PLA induced the transient internalization of TJ proteins in cell-cell junctions via clathrin-mediated endocytosis, subsequently increasing the permeability of the Caco-2 cell monolayer to FD-4 via a paracellular route.

  4. Maternal Dietary L-Arginine and Adverse Birth Outcomes in Dar es Salaam, Tanzania.

    PubMed

    Darling, Anne Marie; McDonald, Chloe R; Urassa, Willy S; Kain, Kevin C; Mwiru, Ramadhani S; Fawzi, Wafaie W

    2017-09-01

    The amino acid arginine is a physiological precursor to nitric oxide, which is a key mediator of embryonic survival, fetal growth, and pregnancy maintenance. We evaluated the association between consumption of the amino acid arginine and the rate of adverse birth outcomes using data from a double-blind, randomized, placebo-controlled micronutrient supplementation trial among pregnant women in Dar es Salaam, Tanzania (2001-2004). Dietary intakes of arginine were assessed using repeated 24-hour recalls that were administered throughout pregnancy. Participants (n = 7,591) were monitored by research midwives throughout follow-up to assess pregnancy outcomes. Cubic-restricted splines and multivariable log-Poisson regression with empirical standard errors were used to estimate the continuous and categorical associations between arginine intake and adverse birth outcomes. Compared with women within the lowest quintile of arginine intake, those within the highest quintile had 0.79 times the risk of preterm birth before 37 weeks (95% confidence interval: 0.63, 1.00; P = 0.03). The continuous associations of arginine intake with preterm birth before 37 weeks and with preterm birth before 34 weeks were characterized by an initial rapid decrease in risk with increasing intake (P for nonlinearity < 0.01). Arginine intake was not associated with fetal loss or giving birth to infants who were born small for their gestational ages. This data suggest that the association between dietary arginine intake and preterm birth warrants further investigation. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Effects of dietary L-arginine on laying performance and antioxidant capacity of broiler breeder hens, eggs, and offspring during the late laying period.

    PubMed

    Duan, Xiaoxue; Li, Feng; Mou, Shaoyang; Feng, Jiawei; Liu, Peifeng; Xu, Liangmei

    2015-12-01

    The effects of maternal L-arginine supplementation on laying performance and the antioxidant capacity of broiler breeder hens, egg yolk, and their one-day-old offspring were investigated. In a 9 wk experiment, 210 60-week-old Arbor Acres healthy female broiler breeders were randomly divided into 5 treatments with 6 replicates of 7 females and fed a corn and soybean meal diet with 5 arginine levels (0.96%, 1.16%, 1.36%, 1.56%, and 1.76% digestible arginine). Laying performance and anti-oxidant capacity of broiler breeder hens, eggs, and offspring were evaluated. Digestible arginine level in the broiler breeder diet had a significant effect on the laying rate (linear and quadratic effect, P<0.0001). The highest laying rate was obtained when the diet with 1.36% digestible arginine was fed. There was a significant effect of digestible arginine level in the broiler breeder diet on the total antioxidant capacity (T-AOC) levels and methane dicarboxylic aldehyde (MDA) concentration in the broiler breeder serum, egg yolk and serum, and liver and breast of one-day-old offspring (linear and quadratic effect, P<0.05). The T-AOC level was highest and the MDA concentration lowest in all tissues when a diet with 1.36% digestible arginine was fed. No difference in glutathione peroxidase (GSH-PX) activity in the broiler breeder serum was observed. There were significant effects of digestible arginine level in the broiler breeder diet on the GSH-PX activity of the egg yolk (linear effect, P<0.01; quadratic effect, P<0.05) and serum, liver, and breast of one-day-old offspring (linear and quadratic effect, P≤0.01). The GSH-PX activity in all tissues measured in this experiment was highest when the dietary digestible arginine was 1.36%. These results indicate that the diet with 1.36% digestible arginine (1,972 mg/d) is optimal to satisfy the nutritional needs of a female broiler breeder during the late laying period.

  6. Nanoscale characterization of effect of L-arginine on Streptococcus mutans biofilm adhesion by atomic force microscopy.

    PubMed

    Sharma, Shivani; Lavender, Stacey; Woo, JungReem; Guo, Lihong; Shi, Wenyuan; Kilpatrick-Liverman, LaTonya; Gimzewski, James K

    2014-07-01

    A major aetiological factor of dental caries is the pathology of the dental plaque biofilms. The amino acid L-arginine (Arg) is found naturally in saliva as a free molecule or as a part of salivary peptides and proteins. Plaque bacteria metabolize Arg to produce alkali and neutralize glycolytic acids, promoting a less cariogenous oral microbiome. Here, we explored an alternative and complementary mechanism of action of Arg using atomic force microscopy. The nanomechanical properties of Streptococcus mutans biofilm extracellular matrix were characterized under physiological buffer conditions. We report the effect of Arg on the adhesive behaviour and structural properties of extracellular polysaccharides in S. mutans biofilms. High-resolution imaging of biofilm surfaces can reveal additional structural information on bacterial cells embedded within the surrounding extracellular matrix. A dense extracellular matrix was observed in biofilms without Arg compared to those grown in the presence of Arg. S. mutans biofilms grown in the presence of Arg could influence the production and/or composition of extracellular membrane glucans and thereby affect their adhesion properties. Our results suggest that the presence of Arg in the oral cavity could influence the adhesion properties of S. mutans to the tooth surface. © 2014 The Authors.

  7. L-Arginine inhibits in vitro nonenzymatic glycation and advanced glycosylated end product formation of human serum albumin.

    PubMed

    Servetnick, D A; Bryant, D; Wells-Knecht, K J; Wiesenfeld, P L

    1996-03-01

    L-Arginine (Arg) has a structure similar to that of aminoguanidine (AG) and may inhibit glycation and advanced glycosylated end product (AGE) formation. Human serum albumin (HSA) (100mg/ml) was incubated for 2 weeks with glucose (200mM) at 37°C or with glucose and equimolar concentrations of Arg, N-α-acetyl Arg, or AG with or without 25mM diethylenetriaminepentaacetic acid (DTPA). In the absence of DTPA, electrospray ionization mass spectrometry showed a 70% reduction of covalently bound glucose in the presence of Arg and a 30% reduction with AG. Digestibility by trypsin of HSA incubated with glucose and Arg was similar to that of HSA incubated alone. This suggests less covalent modification of HSA in the presence of Arg as compared with the absence of Arg. When incubations contained DTPA, autoradiography showed less(14)C labeling of HSA subunits in the presence of Arg and AG. When theα-amino group of Arg was blocked with an acetyl group, labeling was similar to that of HSA incubated with glucose, suggesting involvement of theα-amino group in the inhibition. Fluorescence of HSA at ex370 and em440 was reduced with Arg, but AG was more effective than Arg. These results suggest that Arg, like AG, can inhibit glycation and AGE formation.

  8. Prolonged treatment with N-acetylcysteine and L-arginine restores gonadal function in patients with polycystic ovary syndrome.

    PubMed

    Masha, A; Manieri, C; Dinatale, S; Bruno, G A; Ghigo, E; Martina, V

    2009-12-01

    Nitric oxide (NO) plays a wide spectrum of biological actions including a positive role in oocyte maturation and ovulation. Free radicals levels have been shown elevated in polycystic ovary syndrome (PCOS) and therefore would be responsible for quenching NO that, in turn, would play a role in determining oligo- or amenorrhea connoting PCOS. Eight patients with PCOS displaying oligo-amenorrhea from at least 1 yr underwent a combined treatment with N-acetylcysteine (NAC) (1200 mg/die) plus L-arginine (ARG) (1600 mg/die) for 6 months. Menstrual function, glucose and insulin levels, and, in turn, homeostasis model assessment (HOMA) index were monitored. Menstrual function was at some extent restored as indicated by the number of uterine bleedings under treatment (3.00, 0.18-5.83 vs 0.00, 0.00-0.83; p<0.02). Also, a well-defined biphasic pattern in the basal body temperature suggested ovulatory cycles. The HOMA index decreased under treatment (2.12, 1.46-4.42 vs 3.48, 1.62-5.95; p<0.05). In conclusion, this preliminary, open study suggests that prolonged treatment with NAC+ARG might restore gonadal function in PCOS. This effect seems associated to an improvement in insulin sensitivity.

  9. Conformational dynamics of L-lysine, L-arginine, L-ornithine binding protein reveals ligand-dependent plasticity.

    PubMed

    Silva, Daniel-Adriano; Domínguez-Ramírez, Lenin; Rojo-Domínguez, Arturo; Sosa-Peinado, Alejandro

    2011-07-01

    The molecular basis of multiple ligand binding affinity for amino acids in periplasmic binding proteins (PBPs) and in the homologous domain for class C G-protein coupled receptors is an unsolved question. Here, using unrestrained molecular dynamic simulations, we studied the ligand binding mechanism present in the L-lysine, L-arginine, L-ornithine binding protein. We developed an analysis based on dihedral angles for the description of the conformational changes upon ligand binding. This analysis has an excellent correlation with each of the two main movements described by principal component analysis (PCA) and it's more convenient than RMSD measurements to describe the differences in the conformational ensembles observed. Furthermore, an analysis of hydrogen bonds showed specific interactions for each ligand studied as well as the ligand interaction with the aromatic residues Tyr-14 and Phe-52. Using uncharged histidine tautomers, these interactions are not observed. On the basis of these results, we propose a model in which hydrogen bond interactions place the ligand in the correct orientation to induce a cation-π interaction with Tyr-14 and Phe-52 thereby stabilizing the closed state. Our results also show that this protein adopts slightly different closed conformations to make available specific hydrogen bond interactions for each ligand thus, allowing a single mechanism to attain multiple ligand specificity. These results shed light on the experimental evidence for ligand-dependent conformational plasticity not explained by the previous crystallographic data. Copyright © 2011 Wiley-Liss, Inc.

  10. Investigations on nucleation, HRXRD, optical, piezoelectric, polarizability and Z-scan analysis of L-arginine maleate dihydrate single crystals

    NASA Astrophysics Data System (ADS)

    Sakthy Priya, S.; Alexandar, A.; Surendran, P.; Lakshmanan, A.; Rameshkumar, P.; Sagayaraj, P.

    2017-04-01

    An efficient organic nonlinear optical single crystal of L-arginine maleate dihydrate (LAMD) has been grown by slow evaporation solution technique (SEST) and slow cooling technique (SCT). The crystalline perfection of the crystal was examined using high-resolution X-ray diffractometry (HRXRD) analysis. Photoluminescence study confirmed the optical properties and defects level in the crystal lattice. Electromechanical behaviour was observed using piezoelectric co-efficient (d33) analysis. The photoconductivity analysis confirmed the negative photoconducting nature of the material. The dielectric constant and loss were measured as a function of frequency with varying temperature and vice-versa. The laser damage threshold (LDT) measurement was carried out using Nd:YAG Laser with a wavelength of 1064 nm (Focal length is 35 cm) and the obtained results showed that LDT value of the crystal is high compared to KDP crystal. The high laser damage threshold of the grown crystal makes it a potential candidate for second and higher order nonlinear optical device application. The third order nonlinear optical parameters of LAMD crystal is determined by open-aperture and closed-aperture studies using Z-scan technique. The third order linear and nonlinear optical parameters such as the nonlinear refractive index (n2), two photon absorption coefficient (β), Real part (Reχ3) and imaginary part (Imχ3) of third-order nonlinear optical susceptibility are calculated.

  11. [Effect of L-arginine and the nitric oxide synthase blocker L-NNA on calcium capacity in rat liver mitochondria with differing resistance to hypoxia].

    PubMed

    Kurhaliuk, N M; Ikkert, O V; Vovkanych, L S; Horyn', O V; Hal'kiv, M O; Hordiĭ, S K

    2001-01-01

    The effect of L-arginine and blockator of nitric oxide synthase L-NNA on processes of calcium mitochondrial capacity in liver with different resistance to hypoxia in the experiments with Wistar rats has been studied using the followrng substrates of energy support: succinic, alpha-ketoglutaric acids, alpha-ketolutarate and inhibitor succinatedehydrogenase malonate. As well we used substrates mixtures combination providing for activation of aminotransferase mechanism: glutamate and piruvate, glutamate and malate. It has been shown that L-arginine injection increases calcium mitochondrial capacity of low resistant rats using as substrates the succinate and alpha-ketoglutarate to control meanings of high resistance rats. Effects of donors nitric oxide on this processes limit NO-synthase inhibitor L-NNA.

  12. Effect of doping of KDP crystal with amino acid L-arginine on the strength properties and character of laser damage

    NASA Astrophysics Data System (ADS)

    Dolzhenkova, E. F.; Kostenyukova, E. I.; Bezkrovnaya, O. N.; Pritula, I. M.

    2017-11-01

    Studied were the strength characteristics of KDP crystals doped with L-arginine under a concentrated load and irradiation of the first harmonic YAG:Nd3+ laser. The crystals were obtained by means of the temperature reduction method on a point seed, the content of L-arginine in the aqueous solution being 0.3, 0.4, 1.0 and 1.4 wt%. The character of the dependence of KDP microhardness versus the concentration of amino acid in the crystal was investigated. The regularities of brittle damage of the doped KDP crystal at mechanical testing and laser irradiation were shown to be similar. As confirmed in the study, the planes of easy crack extension in the crystal are {2 2 1}, (1 0 0), and (0 0 1) planes, the cracks mainly propagate parallel to {2 2 1} planes. The mechanical and laser strength values of doped KDP crystals were evaluated.

  13. Analysis of L-citrulline and L-arginine in Ficus deltoidea leaf extracts by reverse phase high performance liquid chromatography

    PubMed Central

    Shafaei, Armaghan; Aisha, Abdalrahim F. A.; Siddiqui, Mohammad Jamshed Ahmad; Ismail, Zhari

    2015-01-01

    Background: Ficus deltoidea (FD) is one of the native plants widely distributed in several countries in Southeast Asia. Previous studies have shown that FD leaf possess antinociceptive, wound healing and antioxidant properties. These beneficial effects have been attributed to the presence of primary and secondary metabolites such as polyphenols, amino acids and flavonoids. Objective: The aim was to develop a reverse phase high-performance liquid chromatography method with ultraviolet detection that involves precolumn derivatisation with O-phthaladehyde for simultaneous analysis of two amino acids L-citrulline and L-arginine in FD leaf extracts. Materials and Methods: An isocratic elution program consisting of methanol: acetonitrile: Water at 45:45:10 v/v (solvent A) and 0.1 M phosphate buffer pH 7.5 (solvent B) at A: B v/v ratio of 80:20 on Zorbax Eclipse C18 SB-Aq column (250 × 4.6 mm, 5 μm) were used. The flow rate was set at 1 ml/min and detection was carried out at 338 nm with 30 min separation time. Results: Good linearity for L-citrulline and L-arginine was obtained in the range 0.1-1000 μg/ml at R2 ≥ 0.998. The limit of detection and limit of quantification values for both L-citrulline and L-arginine were 1 and 5 μg/ml, respectively. The average of recoveries was in the range 94.94-101.95%, with relative standard deviation (%RSD) less than 3%. Intra- and inter-day precision was in the range 96.36-102.43% with RSD less than 2%. Conclusion: All validation parameters of the developed method indicate the method is reliable and efficient for simultaneous determination of L-citrulline and L-arginine for routine analysis of FD. PMID:25598632

  14. Trypanosomatid Infections: How Do Parasites and Their Excreted–Secreted Factors Modulate the Inducible Metabolism of l-Arginine in Macrophages?

    PubMed Central

    Holzmuller, Philippe; Geiger, Anne; Nzoumbou-Boko, Romaric; Pissarra, Joana; Hamrouni, Sarra; Rodrigues, Valérie; Dauchy, Frédéric-Antoine; Lemesre, Jean-Loup; Vincendeau, Philippe; Bras-Gonçalves, Rachel

    2018-01-01

    Mononuclear phagocytes (monocytes, dendritic cells, and macrophages) are among the first host cells to face intra- and extracellular protozoan parasites such as trypanosomatids, and significant expansion of macrophages has been observed in infected hosts. They play essential roles in the outcome of infections caused by trypanosomatids, as they can not only exert a powerful antimicrobial activity but also promote parasite proliferation. These varied functions, linked to their phenotypic and metabolic plasticity, are exerted via distinct activation states, in which l-arginine metabolism plays a pivotal role. Depending on the environmental factors and immune response elements, l-arginine metabolites contribute to parasite elimination, mainly through nitric oxide (NO) synthesis, or to parasite proliferation, through l-ornithine and polyamine production. To survive and adapt to their hosts, parasites such as trypanosomatids developed mechanisms of interaction to modulate macrophage activation in their favor, by manipulating several cellular metabolic pathways. Recent reports emphasize that some excreted–secreted (ES) molecules from parasites and sugar-binding host receptors play a major role in this dialog, particularly in the modulation of the macrophage’s inducible l-arginine metabolism. Preventing l-arginine dysregulation by drugs or by immunization against trypanosomatid ES molecules or by blocking partner host molecules may control early infection and is a promising way to tackle neglected diseases including Chagas disease, leishmaniases, and African trypanosomiases. The present review summarizes recent knowledge on trypanosomatids and their ES factors with regard to their influence on macrophage activation pathways, mainly the NO synthase/arginase balance. The review ends with prospects for the use of biological knowledge to develop new strategies of interference in the infectious processes used by trypanosomatids, in particular for the development of vaccines

  15. Cyclophosphamide induced stomach and duodenal lesions as a NO-system disturbance in rats: L-NAME, L-arginine, stable gastric pentadecapeptide BPC 157.

    PubMed

    Luetic, Krešimir; Sucic, Mario; Vlainic, Josipa; Halle, Zeljka Belosic; Strinic, Dean; Vidovic, Tinka; Luetic, Franka; Marusic, Marinko; Gulic, Sasa; Pavelic, Tatjana Turudic; Kokot, Antonio; Seiwerth, Ranka Serventi; Drmic, Domagoj; Batelja, Lovorka; Seiwerth, Sven; Sikiric, Predrag

    2017-04-01

    We revealed a new point with cyclophosphamide (150 mg/kg/day intraperitoneally for 7 days): we counteracted both rat stomach and duodenal ulcers and increased NO- and MDA-levels in these tissues. As a NO-system effect, BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once a day or in drinking water, till the sacrifice) attenuated the increased NO- and MDA-levels and nullified, in rats, severe cyclophosphamide-ulcers and even stronger stomach and duodenal lesions after cyclophosphamide + L-NAME (5 mg/kg intraperitoneally once a day). L-arginine (100 mg/kg intraperitoneally once a day not effective alone) led L-NAME-values only to the control values (cyclophosphamide + L-NAME + L-arginine-rats). Briefly, rats were sacrificed at 24 h after last administration on days 1, 2, 3, or 7, and assessment included sum of longest lesions diameters (mm) in the stomach and duodenum, oxidative stress by quantifying thiobarbituric acid reactivity as malondialdehyde equivalents (MDA), NO in stomach and duodenal tissue samples using the Griess reaction. All these parameters were highly exaggerated in rats who underwent cyclophosphamide treatment. We identified high MDA-tissue values, high NO-tissue values, ulcerogenic and beneficial potential in cyclophosphamide-L-NAME-L-arginine-BPC 157 relationships. This suggests that in cyclophosphamide damaged rats, NO excessive release generated by the inducible isozyme, damages the vascular wall and other tissue cells, especially in combination with reactive oxygen intermediates, while failing endothelial production and resulting in further aggravation by L-NAME which was inhibited by L-arginine. Finally, BPC 157, due to its special relations with NO-system, may both lessen increased MDA- and NO-tissues values and counteract effects of both cyclophosphamide and L-NAME on stomach and duodenal lesions.

  16. Comparative study on the protective role of vitamin C and L-arginine in experimental renal ischemia reperfusion in adult rats.

    PubMed

    Mohamed, Abd El-Hamid A; Lasheen, Noha N

    2014-01-01

    Ischemia reperfusion (I/R) injury is a main cause of transplanted kidney dysfunction and rejection. Reactive oxygen species (ROS) play a causal role in cellular damage induced by I/R. Antioxidant vitamins and Nitric oxide (NO) were postulated to play renoprotective effects against I/R. This study compares the protective effects of vitamin C with that of the nitric oxide donor, L-arginine, on renal I/R injury in adult rats. The study was performed on 50 adult Wistar rats of both sexes, divided into 5 groups: I: Control group, receive daily intraperitoneal (i.p.) saline for 3 days. II: Renal I/R group, received i.p saline for 3 days and subjected to renal I/R. III: L-arginine Pretreated, 400 mg/kg/day i.p. for 3 days prior to I/R. IV: Vitamin C Pretreated, 500 mg/kg/day i.p. 24 hours prior to I/R. V: combined L-arginine and Vitamin C Pretreated, exposed to Renal I/R group. At the end of the experiment, plasma urea and creatinine were determined. Kidney tissue malondialdehyde (MDA), NO, catalase and superoxide dismutase (SOD) activity were measured and kidneys were examined histologically. I/R group showed significant increase in plasma urea, creatinine, and renal MDA, and a significant decrease in renal catalase with marked necrotic epithelial cells and infiltration by inflammatory cells in kidney section compared to the control group. All the treated groups showed significant decrease in urea, creatinine, and MDA, and a significant increase in catalase with less histopathological changes in kidney sections compared to I/R group. However, significant improvements in urea, MDA, and catalase were found in vitamin C pretreated and combined treated groups than L-arginine pretreated group. Oxidative stress is the primary element involved in renal I/R injury. So, antioxidants play an important renoprotective effects than NO donors.

  17. l-Arginine normalizes NOS activity and zinc-MT homeostasis in the kidney of mice chronically exposed to inorganic mercury.

    PubMed

    Piacenza, Francesco; Malavolta, Marco; Cipriano, Catia; Costarelli, Laura; Giacconi, Robertina; Muti, Elisa; Tesei, Silvia; Pierpaoli, Sara; Basso, Andrea; Bracci, Massimo; Bonacucina, Viviana; Santarelli, Lory; Mocchegiani, Eugenio

    2009-09-28

    Inorganic mercury (HgCl2) exposure provokes damage in many organs, especially kidney. Inducible nitric oxide synthase (iNOS) expression, total NOS activity and the profiles of zinc (Zn), copper (Cu) and Hg as well as their distribution when bound to specific intracellular proteins, including metallothioneins (MT), were studied during HgCl2 exposure and after l-arginine treatment in C57BL/6 mouse kidney. HgCl2 exposure modulates differently iNOS expression and NOS activity, increasing iNOS expression but, conversely, decreasing total NOS activity in the mouse kidney. Moreover, during Hg exposure an increased MT production occurs. The kidney damage leads to a loss of urinary proteins, increased plasma creatinine and high Zn mobilization with consequent increased urinary Zn excretion. l-arginine treatment recovers NOS activity and induces a normalization of MT induction, plasma creatinine values and urinary proteins excretion, suggesting that l-arginine may limit kidney damages by Hg exposure.

  18. [State of mitochondrial respiration and calcium capacity in livers of rats with different resistance to hypoxia after injections of L-arginine].

    PubMed

    Kurhaliuk, N M

    2001-01-01

    In experiments on rats with different resistance to hypoxia are investigated processes of mitochondrial respiration, oxidative phosphorylation and calcium capacity in liver under precursor nitric oxide L-arginine (600 mg/kg) and blockator nitric oxide synthase L-NNA (35 mg/kg) injections. We are used next substrates of oxidation: 0.35 mM succinate, 1 mM alpha-ketoglutarate, 1 mM alpha-ketoglutarate and 2 mM malonic acid. Increasing of ADP-stimulation respiration states under exogenous L-arginine injection, decreasing efficacy of respiration processes (respiration control on Chance and ADP/O) under such substrates oxidation, testify to oxide energy support decreasing and reversing nitric oxide inhibit in such conditions. This will be used as mechanism cell regulation succinate dehydrogenase activity. It has shown that L-arginine injection increase calcium mitochondrial capacity low resistance to hypoxia rats using substrates of oxidation succinate and alpha-ketoglutarate to control meanings of high resistance rats. Effects of nitric oxide precursor influence on this processes limit NO-synthase inhibitor L-NNA.

  19. Direct cytosolic delivery of cargoes in vivo by a chimera consisting of D- and L-arginine residues.

    PubMed

    Ma, Yan; Gong, Cheng; Ma, Yilong; Fan, Fengkai; Luo, Meijie; Yang, Fei; Zhang, Yu-Hui

    2012-09-10

    The ability of cell-penetrating peptides (CPPs) to deliver a range of membrane-impermeable molecules into living cells makes them attractive potential vehicles for therapeutics. However, in vivo, the efficiency of CPP delivery to the cytosol remains unsatisfactory owing to endosomal entrapment and/or systemic toxicity, which severely restrict their bioavailability and efficacy in in vivo applications. In this study, we developed a series of novel chimeras consisting of various numbers of d- and l-arginine residues and investigated their cellular uptake behaviors and systemic toxicities. We demonstrated that the intracellular distribution, uptake efficiency, and systemic toxicity of these oligoarginines were all significantly affected by the number of d-arginine residues in the peptide sequence. We also found that a hybrid peptide, (rR)(3)R(2), possessed low systemic toxicity, high uptake efficiency, and, remarkably, achieved efficient cytosolic delivery not only in cultured cells but also in living tissue cells in mice after intravenous injection, implying that this heterogeneous motif might have promising applications in the delivery of cargoes of small sizes directed to cytosolic targets in vivo. Our studies into the uptake mechanism of (rR)(3)R(2) indicate that its cellular uptake was not affected by pharmacological or physical inhibitors of endocytosis but by the elimination of the membrane potential, suggesting that (rR)(3)R(2) does not enter the cells via endocytosis but rather through direct membrane translocation driven by the membrane potential. The results here might provide useful guidelines for the design and application of CPPs in drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Potential Role of L-Arginine and Vitamin E Against Bone Loss Induced by Nano-Zinc Oxide in Rats.

    PubMed

    Abdelkarem, Hala M; Fadda, Laila H; El-Sayed, Eman M; Radwan, Omyma K

    2018-05-04

    The purpose of this study was to illustrate the effects of zinc oxide nanoparticles (ZnO-NPs) administration on bone turnover and bone resorbing agents in rats and how L-arginine (L-arg) or vitamin E (vit E) co-administrations might affect them. Fasting rats were randomly divided into four groups (n = 10): G1-normal healthy animals; G2-ZnO-NPs-exposed rats (600 mg/kg - 1/day -1 ); G3-ZnO-NPs-exposed rats co-administrated L-arg (200 mg/kg - 1/day -1 ); G4-ZnO-NPs-exposed rats co-administrated vit E (200 mg/kg - 1/day -1 ). The ingredients were orally administered daily. The body weight and food consumption of rats were recorded during the administration period and the experiment continued for three consecutive weeks. The results demonstrated that ZnO-NPs administration induced bone loss in rats as manifested by reduced activity of bone alkaline phosphatase (B-ALP) and increased level of C-terminal peptide type I collagen (CTx). The increase of inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) by ZnO-NPs suggests that deleterious effects of ZnO-NPs on bone turnover were, in part, due to inflammation. Confirming to this suggestion, both L-arg and vit E reduced TNF-α and IL-6 levels and consequently decreased bone resorption as indicated by reduced serum CTx level. This study proved that ZnO-NPs can induce bone turnover, which may be reduced by L-arg or vit.E co-administration, partly by anti-inflammatory mechanism.

  1. Hypothermia induced by adenosine 5'-monophosphate attenuates injury in an L-arginine-induced acute pancreatitis rat model.

    PubMed

    Wang, Yunlong; Guo, Weiting; Li, Yuan; Pan, Xinting; Lv, Wenshan; Cui, Lingling; Li, Changgui; Wang, Yangang; Yan, Shengli; Zhang, Jidong; Liu, Bin

    2014-04-01

    This study sought to investigate the effects of hypothermia induced by adenosine 5'-monophosphate (5'-AMP) on L-arginine (L-Arg)-induced acute pancreatitis in rats. The rats were divided into four groups: the control group, the acute pancreatitis group, the 5'-AMP pretreatment group, and the 5'-AMP posttreatment group. Rats in all groups, except for the control group, received two injections of 2.5 g/kg body weight (intraperitoneally) L-Arg, with an interval of 1 h between the injections. Subsequently, the rats were observed to assess whether hypothermia induced by 5'-AMP could effectively inhibit inflammation associated with L-Arg-induced acute pancreatitis in rats. Hypothermia induced by 5'-AMP produced protective effects in our acute pancreatitis model. These effects exhibited the following manifestations: (i) a significant reduction in rat mortality rates; (ii) a significant decrease in the occurrence of pancreatic edema; (iii) significant reductions in serum amylase (P < 0.001), interleukin-6 (P < 0.001), interleukin-1β (P < 0.001) and tumor necrosis factor-α (P < 0.001); (iv) the significant inhibition of nuclear factor-κB (NF-κB) activation in rats that were pre- and posttreated with 5'-AMP compared with rats that were only injected with L-Arg; and (v) significant decreases in the occurrence of pancreatic interstitial edema, inflammatory cell infiltration, hemorrhage, and acinar cell necrosis. Hypothermia induced by 5'-AMP could inhibit the acute inflammatory reaction and NF-κB activation associated with acute pancreatitis. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  2. The protective role of melatonin on L-arginine-induced acute pancreatitis in adult male albino rats.

    PubMed

    Sadek, A S; Khattab, R T

    2017-01-01

    Acute pancreatitis (AP) is an inflammatory disease that has an increasing incidence worldwide. AP is associated with high morbidity and mortality rates ranging 15-40% in its severe form. Oxidative stress plays an important role in pancreatic acinar cell injury in case of AP. Melatonin (Mel) is proven to have both antioxidant and anti-inflammatory effects. The aim of the work was to investigate the protective role of Mel against L-arginine (L-arg)-induced AP in adult male albino rats. Thirty-six adult male albino rats were used in this study. Animals were divided into four groups; Control group (Group A; n = 6), Mel group (Group B; n = 6), L-arg group (Group C; n = 12) receiving two doses of L-arg injection with 1 h interval in-between, and L-arg+Mel group (Group D; n = 12) receiving Mel 1 h after each L-arg injection. 24 h after the second L-arg injection, the serum levels of amylase (AM), lipase (LP), interleukin-6 (IL-6) and tumour necrotic factor-alpha (TNF-α) were determined. Then, pancreatic specimens were processed for histological and immunohistochemical staining with vascular endothelial growth factor (VEGF) and the area percentage of VEGF and collagen content were measured by digital image analysis. Microscopic examination revealed that animals received L-arg only (Group C) showed loss of the pancreatic lobular architecture with marked fibrosis, acinar degeneration, inflammatory reaction and marked oedema with vascular congestion. Also, L-arg-induced AP caused a significant elevation of the serum levels of AM, LP, IL-6. All these histo-pathological and serological parameters were markedly improved by Mel administration. Melatonin exhibits strong therapeutic effects in the course of AP. Hence, the use of Mel as adjuvant treatment in AP is recommended.

  3. Improvement of the intracellular environment for enhancing l-arginine production of Corynebacterium glutamicum by inactivation of H2O2-forming flavin reductases and optimization of ATP supply.

    PubMed

    Man, Zaiwei; Rao, Zhiming; Xu, Meijuan; Guo, Jing; Yang, Taowei; Zhang, Xian; Xu, Zhenghong

    2016-11-01

    l-arginine, a semi essential amino acid, is an important amino acid in food flavoring and pharmaceutical industries. Its production by microbial fermentation is gaining more and more attention. In previous work, we obtained a new l-arginine producing Corynebacterium crenatum (subspecies of Corynebacterium glutamicum) through mutation breeding. In this work, we enhanced l-arginine production through improvement of the intracellular environment. First, two NAD(P)H-dependent H 2 O 2 -forming flavin reductases Frd181 (encoded by frd1 gene) and Frd188 (encoded by frd2) in C. glutamicum were identified for the first time. Next, the roles of Frd181 and Frd188 in C. glutamicum were studied by overexpression and deletion of the encoding genes, and the results showed that the inactivation of Frd181 and Frd188 was beneficial for cell growth and l-arginine production, owing to the decreased H 2 O 2 synthesis and intracellular reactive oxygen species (ROS) level, and increased intracellular NADH and ATP levels. Then, the ATP level was further increased by deletion of noxA (encoding NADH oxidase) and amn (encoding AMP nucleosidase), and overexpression of pgk (encoding 3-phosphoglycerate kinase) and pyk (encoding pyruvate kinase), and the l-arginine production and yield from glucose were significantly increased. In fed-batch fermentation, the l-arginine production and yield from glucose of the final strain reached 57.3g/L and 0.326g/g, respectively, which were 49.2% and 34.2% higher than those of the parent strain, respectively. ROS and ATP are important elements of the intracellular environment, and l-arginine biosynthesis requires a large amount of ATP. For the first time, we enhanced l-arginine production and yield from glucose through reducing the H 2 O 2 synthesis and increasing the ATP supply. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  4. How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio.

    PubMed

    Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

    2018-05-01

    The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O 2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

  5. How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio

    NASA Astrophysics Data System (ADS)

    Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

    2017-12-01

    The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

  6. Effect of L-arginine and selenium added to a hypocaloric diet enriched with legumes on cardiovascular disease risk factors in women with central obesity: a randomized, double-blind, placebo-controlled trial.

    PubMed

    Alizadeh, Mohammad; Safaeiyan, Abdolrasoul; Ostadrahimi, Alireza; Estakhri, Rassul; Daneghian, Sevana; Ghaffari, Aida; Gargari, Bahram Pourghassem

    2012-01-01

    We aimed to discover if L-arginine and selenium alone or together can increase the effect of a hypocaloric diet enriched in legumes (HDEL) on central obesity and cardiovascular risk factors in women with central obesity. This randomized, double-blind, placebo-controlled trial was undertaken in 84 premenopausal women with central obesity. After a 2-week run-in period on an isocaloric diet, participants were randomly assigned to a control diet (HDEL), L-arginine (5 g/day) and HDEL, selenium (200 μg/day) and HDEL or L-arginine, selenium and HDEL for 6 weeks. Cardiovascular risk factors were assessed before intervention and 3 and 6 weeks afterwards. After 6 weeks, L-arginine had significantly reduced waist circumference (WC); selenium had significantly lowered fasting concentrations of serum insulin and the homeostasis model assessment of insulin resistance index; the interaction between L-arginine and selenium significantly reduced the fasting concentration of nitric oxides (NO(x)), and HDEL lowered triglycerides (TG) and WC and significantly increased the fasting concentration of NO(x). HDEL reduced high-sensitivity C-reactive protein levels in the first half of the study and returned them to basal levels in the second half. These data indicate the beneficial effects of L-arginine on central obesity, selenium on insulin resistance and HDEL on serum concentrations of NO(x) and TG. Copyright © 2012 S. Karger AG, Basel.

  7. How does spa treatment affect cardiovascular function and vascular endothelium in patients with generalized osteoarthritis? A pilot study through plasma asymmetric di-methyl arginine (ADMA) and L-arginine/ADMA ratio

    NASA Astrophysics Data System (ADS)

    Karaarslan, Fatih; Ozkuk, Kagan; Seringec Karabulut, Serap; Bekpinar, Seldag; Karagulle, Mufit Zeki; Erdogan, Nergis

    2018-05-01

    The study aims to investigate the effect of spa treatment on vascular endothelium and clinical symptoms of generalized osteoarthritis. Forty generalized osteoarthritis (GOA) patients referred to a government spa hospital, and 40 GOA patients followed on university hospital locomotor system disease ambulatory clinics were included as study and control groups, respectively. Study group received spa treatment including thermal water baths, physical therapy modalities, and exercises. Control group was followed with home exercises for 15 days. Plasma ADMA, L-arginine, L-arginine/ADMA ratio, routine blood analyses, 6-min walking test, including fingertip O2 saturation, systolic/diastolic blood pressure, and pulse rate, were measured at the beginning and at the end of treatment. Groups were evaluated with VAS pain, patient, and physician global assessment; HAQ; and WOMAC at the beginning, at the end, and after 1 month of treatment. In study group, L-arginine and L-arginine/ADMA ratio showed statistically significant increase after treatment. Plasma ADMA levels did not change. There is no significant difference in intergroup comparison. Study group displayed statistically significant improvements in all clinical parameters. The study showed that spa treatment does not cause any harm to the vascular endothelium through ADMA. Significant increase in plasma L-arginine and L-arginine/ADMA ratio suggests that balneotherapy may play a preventive role on cardiovascular diseases. Balneotherapy provides meaningful improvements on clinical parameters of GOA.

  8. Studies of vascular tolerance to nitroglycerin: effects of N-acetylcysteine, NG-monomethyl L-arginine, and endothelin-1.

    PubMed

    Lawson, D L; Haught, W H; Mehta, P; Mehta, J L

    1996-09-01

    Development of vascular tolerance to nitroglycerin (NTG) has been attributed to sulfhydryl (SH) depletion, guanylate cyclase desensitization, or both. Controversy regarding the precise contribution of these mechanisms may be due to variations in experimental design. To examine further the biochemical basis of NTG tolerance, norepinephrine (NE)-precontracted rat aortic rings were exposed to NTG (10(-5)M), which resulted in 84 +/- 6% relaxation. Other rings were first superfused with NTG (10(-6)M) and then contracted with NE. These rings showed a marked tolerance to the vasorelaxant effects of NTG (maximal relaxation 20 +/- 5%, n = 15, p < 0.001 vs. control rings). Similar tolerance to NTG was observed when the vascular rings were first superfused with acetylcholine (ACh 10(-6)M), indicating cross-tolerance between ACh and NTG. Treatment of NTG-tolerant rings with N-acetylcysteine (NAC) (10(-5)M) did not restore vascular smooth muscle (VSM) relaxation in response to NTG (maximal relaxation 23 +/- 5%, n = 8), suggesting that SH depletion may not be the basis of NTG tolerance in these experiments. Parallel sets of NTG-tolerant aortic rings were contracted with endothelin-1 (ET-1, n = 5) or the endothelium-derived relaxing factor (EDRF) synthase inhibitor NG-monomethyl L-arginine (L-NMMA, 10(-4)M, n = 8). In both ET-1- and L-NMMA-contracted rings, vascular relaxation in response to NTG was preserved (80 +/- 6 and 88 +/- 8% relaxation, respectively). Measurement of cyclic GMP in aortic rings showed marked accumulation on initial exposure of tissues to NTG (310 +/- 10 fmol/mg), whereas the NTG-tolerant rings showed much less cyclic GMP accumulation (48 +/- 29 fmol/mg). Rings contracted with L-NMMA or ET-1, but not NE, accumulated cyclic GMP when exposed to NTG (280 +/- 20 fmol/mg). These data indicate that NTG tolerance develops on exposure of vascular rings superfused with NTG or ACh and is probably not related to tissue SH depletion. Contraction of NTG-tolerant rings

  9. A role for serotonin in the antidepressant activity of NG-Nitro-L-arginine, in the rat forced swimming test.

    PubMed

    Gigliucci, Valentina; Buckley, Kathleen Niamh; Nunan, John; O'Shea, Karen; Harkin, Andrew

    2010-02-01

    The present study determined regional serotonin (5-HT) synthesis and metabolism changes associated with the nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine (L-NA) and the influence of 5-HT receptor blockade in the antidepressant-like actions of L-NA in the forced swimming test (FST). Regional effects of L-NA (5,10 and 20mg/kg i.p.) on tryptophan hydroxylase (TPH) activity, the rate limiting enzyme for 5-HT synthesis, were determined by measuring accumulation of the transient intermediate 5-hydoxytryptophan (5-HTP) following in vivo administration of the amino acid decarboxylase inhibitor, NSD 1015 (100mg/kg). L-NA (5-20mg/kg) dose dependently increased 5-HTP accumulation, particularly in the amygdaloid cortex, following exposure to the FST. L-NA also provoked an increase in regional brain 5-HIAA concentrations and in the 5-HIAA:5-HT metabolism ratio. Co-treatment with NSD-1015 failed to consistently modify the antidepressant-like effects of L-NA in the FST. Sub-active doses of L-NA (1mg/kg) and the 5-HT re-uptake inhibitor fluoxetine (2.5mg/kg) acted synergistically to increase swimming in the test. Co-treatment with the non-selective 5-HT receptor antagonist metergoline (1, 2 and 4mg/kg), attenuated the L-NA (20mg/kg)-induced reduction in immobility and increase in swimming behaviours. Metergoline alone however provoked an increase in immobility and reduction in swimming behaviours in the test. A similar response was obtained following co-treatment with the preferential 5-HT(2A) receptor antagonist ketanserin (5mg/kg) and the 5-HT(2C) receptor antagonist RO-430440 (5mg/kg). Co-treatment with the 5-HT(1A) receptor antagonist WAY 100635 (0.3mg/kg) or the 5-HT(1B) receptor antagonist GR 127935 (4mg/kg) failed to influence the antidepressant-like activity of L-NA. Taken together these data provide further support for a role for 5-HT in the antidepressant-like properties of NOS inhibitors. Copyright 2009 Elsevier Inc. All rights reserved.

  10. Arginine supplementation induces myoblast fusion via augmentation of nitric oxide production.

    PubMed

    Long, Jodi H D; Lira, Vitor A; Soltow, Quinlyn A; Betters, Jenna L; Sellman, Jeff E; Criswell, David S

    2006-01-01

    The semi-essential amino acid, L-arginine (L-Arg), is the substrate for endogenous synthesis of nitric oxide, a molecule that is involved in myoblast proliferation and fusion. Since L-Arg supply may limit nitric oxide synthase (NOS) activity in endothelial cells, we examined L-Arg supplementation in differentiating mouse myoblasts and tested the hypothesis that L-Arg exerts direct effects on myoblast fusion via augmentation of endogenous nitric oxide production. C(2)C(12) myoblasts in differentiation media received one of the following treatments for 120 h: 1 mM L-Arg, 0.1 mM N-nitro-L-arginine methyl ester (L-NAME), L-Arg + L-NAME, 10 mM L-Lysine, or no supplement (Control). Cultures were fixed and stained with hematoxylin and eosin for microphotometric image analysis of myotube density, nuclear density, and fusion index (% of total nuclei in myotubes). Endogenous production of nitric oxide during the treatment period peaked between 24 and 48 h. L-Arg amplified nitric oxide production between 0 and 24 h and increased myotube density, total nuclei number, and nuclear fusion index. These L-Arg effects were prevented by the NOS inhibitor, L-NAME. Further, L-Lysine, a competitive inhibitor of L-Arg uptake, repressed nitric oxide production and reduced myotube density and fusion index. In summary, L-Arg augments myotube formation and increases nitric oxide production in a process limited by cellular L-Arg uptake.

  11. Structure-based molecular design for thermostabilization of N-acetyltransferase Mpr1 involved in a novel pathway of L-arginine synthesis in yeast.

    PubMed

    Nasuno, Ryo; Hirase, Saeka; Norifune, Saki; Watanabe, Daisuke; Takagi, Hiroshi

    2016-02-01

    Previously, N-Acetyltransferase Mpr1 was suggested to be involved in a novel pathway of L-arginine biosynthesis in yeast. Our recent crystallographic analysis demonstrated that the overall structure of Mpr1 is a typical folding among proteins in the Gcn5-related N-acetyltransferase superfamily, and also provided clues to the design of mutations for improvement of the enzymatic functions. Here, we constructed new stable variants, Asn203Lys- and Asn203Arg-Mpr1, which exhibited 2.4-fold and 2.2-fold longer activity half-lives than wild-type Mpr1, respectively, by structure-based molecular design. The replacement of Asn203 with a basic amino acid was suggested to stabilize α-helix 2, which is important for the Mpr1 structure, probably by neutralizing its dipole. In addition, the combination of two amino acid substitutions at positions 65 and 203 in Mpr1, Phe65Leu, which was previously isolated by the screening from PCR random mutagenesis library of MPR1, and Asn203Lys or Asn203Arg, led to further stabilization of Mpr1. Our growth assay suggests that overexpression of the stable Mpr1 variants increase L-arginine synthesis in yeast cells. Our finding is the first report on the rational engineering of Mpr1 for thermostabilization and could be useful in the construction of new yeast strains with higher L-arginine synthetic activity and also improved fermentation ability. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  12. Inhibition of the L-arginine-nitric oxide pathway mediates the antidepressant effects of ketamine in rats in the forced swimming test.

    PubMed

    Zhang, Guang-Fen; Wang, Nan; Shi, Jin-Yun; Xu, Shi-Xia; Li, Xiao-Min; Ji, Mu-Huo; Zuo, Zhi-Yi; Zhou, Zhi-Qiang; Yang, Jian-Jun

    2013-09-01

    Converging evidence shows that the acute administration of a sub-anaesthetic dose ketamine produces fast-acting and robust antidepressant properties in patients suffering from major depressive disorder. However, the underlying mechanisms have not been fully elucidated. The present study aimed to investigate the role of the L-arginine-nitric oxide pathway in the antidepressant effects of ketamine in rats performing the forced swimming test (FST). Ketamine (10 mg/kg) significantly decreased immobility times in the FST and the activities of total nitric oxide synthases (T-NOS), inducible NOS (iNOS), and endothelial NOS (eNOS) in the rat hippocampus. Interestingly, the plasma activities of T-NOS, iNOS, and eNOS increased after administration of ketamine. Furthermore, the activities of neuronal NOS (nNOS) did not change significantly in either the hippocampus or plasma after ketamine administration. The antidepressant effects of ketamine were prevented by pre-treatment with l-arginine (750 mg/kg). Pre-treatment with the NOS inhibitor L-NG-nitroarginine methyl ester at a sub-antidepressant dose of 50 mg/kg and ketamine at a sub-antidepressant dose of 3 mg/kg reduced immobility time in the FST compared to treatment with either drug alone. None of the drugs affected crossing and rearing scores in the open field test. These results suggest that the L-arginine-nitric oxide pathway is involved in the antidepressant effects of ketamine observed in rats in the FST and this involvement is characterised by the inhibition of brain T-NOS, iNOS, and eNOS activities. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Metabolically induced heteroplasmy shifting and L-arginine treatment reduce the energetic defect in a neuronal-like model of MELAS

    PubMed Central

    Desquiret-Dumas, Valerie; Gueguen, Naig; Barth, Magalie; Chevrollier, Arnaud; Hancock, Saege; Wallace, Douglas C; Amati-Bonneau, Patrizia; Henrion, Daniel; Bonneau, Dominique; Reynier, Pascal; Procaccio, Vincent

    2012-01-01

    The m.3243A>G variant in the mitochondrial tRNALeu (UUR) gene is a common mitochondrial DNA (mtDNA) mutation. Phenotypic manifestations depend mainly on the heteroplasmy, i.e. the ratio of mutant to normal mtDNA copies. A high percentage of mutant mtDNA is associated with a severe, life-threatening neurological syndrome known as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). MELAS is described as a neurovascular disorder primarily affecting the brain and blood vessels, but the pathophysiology of the disease is poorly understood. We developed a series of cybrid cell lines at two different mutant loads: 70% and 100% in the nuclear background of a neuroblastoma cell line (SH-SY5Y). We investigated the impact of the mutation on the metabolism and mitochondrial respiratory chain activity of the cybrids. The m.3243A>G mitochondrial mutation induced a metabolic switch towards glycolysis in the neuronal cells and produced severe defects in respiratory chain assembly and activity. We used two strategies to compensate for the biochemical defects in the mutant cells: one consisted of lowering the glucose content in the culture medium, and the other involved the addition of L-arginine. The reduction of glucose significantly shifted the 100% mutant cells towards the wild-type, reaching a 90% mutant level and restoring respiratory chain complex assembly. The addition of L-arginine, a nitric oxide (NO) donor, improved complex I activity in the mutant cells in which the defective NO metabolism had led to a relative shortage of NO. Thus, metabolically induced heteroplasmy shifting and L-arginine therapy may constitute promising therapeutic strategies against MELAS. PMID:22306605

  14. Ilex paraguariensis hydroalcoholic extract exerts antidepressant-like and neuroprotective effects: involvement of the NMDA receptor and the L-arginine-NO pathway.

    PubMed

    Ludka, Fabiana K; Tandler, Lori de Fátima; Kuminek, Gislaine; Olescowicz, Gislaine; Jacobsen, Jonatha; Molz, Simone

    2016-06-01

    Ilex paraguariensis St. Hilaire (Aquifoliaceae) is a typical plant from South America. Preclinical studies have reported the effect of I. paraguariensis-based preparations on different alterations in the brain. This study aimed to examine the antidepressant-like and neuroprotective effects of I. paraguariensis hydroalcoholic extract (IpHE). The role of the N-methyl-D-aspartate receptor and the L-arginine-nitric oxide pathway in the IpHE antidepressant-like effect was also evaluated. Using the tail suspension test, we showed that IpHE (0.1-10 mg/kg, orally) exerts an antidepressant-like effect similar to that of ketamine (1 mg/kg, intraperitoneally). The antidepressant-like effect depends on the N-methyl-D-aspartate receptor and L-arginine-nitric oxide pathway modulation as we observed a combinatory effect using subeffective doses of IpHE (0.01 mg/kg, orally) and ketamine (0.1 mg/kg, intraperitoneally) or MK-801 (0.001 mg/kg, intraperitoneally). Also, pretreatment of mice with L-arginine (750 mg/kg, intraperitoneally) abolished the antidepressant-like effect of IpHE. This effect coincides with the neuroprotective effect, given that glutamate toxicity (10 mmol/l) did not decrease cell viability in hippocampal or cortical slices from IpHE-treated mice. The chromatographic profile of IpHE showed the presence of the methylxanthines caffeine and theobromine. Administration of methylxanthines (2.7 µg/kg) in mice produced an antidepressant-like effect, but not neuroprotection. We suggest that methylxanthines are at least in part responsible for the antidepressant-like effect of IpHE; further studies are necessary to determine the biological compounds responsible for the neuroprotective effect.

  15. L-Arginine modified multi-walled carbon nanotube/sulfonated poly(ether ether ketone) nanocomposite films for biomedical applications

    NASA Astrophysics Data System (ADS)

    Kaya, Hatice; Bulut, Osman; Kamali, Ali Reza; Ege, Duygu

    2018-06-01

    Favorable implant-tissue interactions are crucial to achieve successful osseointegration of the implants. Poly(ether ether ketone) (PEEK) is an interesting alternative to titanium in orthopedics because of its low cost, high biocompatibility and comparable mechanical properties with cancellous bone. Despite these advantages; however, the untreated surface of PEEK fails to osseointegrate due to its bioinert and hydrophobic behavior. This paper deals with the surface modification of PEEK with a novel method. For this, PEEK was first treated with concentrated sulfuric acid to prepare sulfonated PEEK (SPEEK) films using a solvent casting method. Then, 1 and 2 wt% multi-walled carbon nanotube was incorporated into SPEEK to form nanocomposite films. The samples were characterized with Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy. After successful preparation of the nanocomposite films, L-arginine was covalently conjugated on the nanocomposite films to further improve their surface properties. Subsequently, the samples were characterized using X-ray Photoemission Spectroscopy (XPS), water contact angle measurements and Atomic Force Microscopy (AFM) and Dynamic Mechanical Thermal Analysis (DMTA). Finally, cell culture studies were carried out by using Alamar Blue assay to evaluate the biocompatibility of the films. The results obtained indicate the successful preparation of L-arginine-conjugated MWCNT/SPEEK nanocomposite films. The modified surface shows potential to improve implants' mechanical and biological performances.

  16. Atomic force microscopic study of step bunching and macrostep formation during the growth of L-arginine phosphate monohydrate single crystals

    NASA Astrophysics Data System (ADS)

    Sangwal, K.; Torrent-Burgues, J.; Sanz, F.; Gorostiza, P.

    1997-02-01

    The experimental results of the formation of step bunches and macrosteps on the {100} face of L-arginine phosphate monohydrate crystals grown from aqueous solutions at different supersaturations studied by using atomic force microscopy are described and discussed. It was observed that (1) the step height does not remain constant with increasing time but fluctuates within a particular range of heights, which depends on the region of step bunches, (2) the maximum height and the slope of bunched steps increases with growth time as well as supersaturation used for growth, and that (3) the slope of steps of relatively small heights is usually low with a value of about 8° and does not depend on the region of formation of step bunches, but the slope of steps of large heights is up to 21°. Analysis of the experimental results showed that (1) at a particular value of supersaturation the ratio of the average step height to the average step spacing is a constant, suggesting that growth of the {100} face of L-arginine phosphate monohydrate crystals occurs by direct integration of growth entities to growth steps, and that (2) the formation of step bunches and macrosteps follows the dynamic theory of faceting, advanced by Vlachos et al.

  17. Interfacial electrostatics of poly(vinylamine hydrochloride), poly(diallyldimethylammonium chloride), poly-l-lysine, and poly-l-arginine interacting with lipid bilayers.

    PubMed

    McGeachy, A C; Dalchand, N; Caudill, E R; Li, T; Doğangün, M; Olenick, L L; Chang, H; Pedersen, J A; Geiger, F M

    2018-04-25

    Charge densities of cationic polymers adsorbed to lipid bilayers are estimated from second harmonic generation (SHG) spectroscopy and quartz crystal microbalance with dissipation monitoring (QCM-D) measurements. The systems surveyed included poly(vinylamine hydrochloride) (PVAm), poly(diallyldimethylammonium chloride) (PDADMAC), poly-l-lysine (PLL), and poly-l-arginine (PLR), as well as polyalcohol controls. Upon accounting for the number of positive charges associated with each polyelectrolyte, the binding constants and apparent free energies of adsorption as estimated from SHG data are comparable despite differences in molecular masses and molecular structure, with ΔGads values of -61 ± 2, -58 ± 2, -57 ± 1, -52 ± 2, -52 ± 1 kJ mol-1 for PDADMAC400, PDADMAC100, PVAm, PLL, and PLR, respectively. Moreover, we find charge densities for polymer adlayers of approximately 0.3 C m-2 for poly(diallyldimethylammonium chloride) while those of poly(vinylamine) hydrochloride, poly-l-lysine, and poly-l-arginine are approximately 0.2 C m-2. Time-dependent studies indicate that polycation adsorption to supported lipid bilayers is only partially reversible for most of the polymers explored. Poly(diallyldimethylammonium chloride) does not demonstrate reversible binding even over long timescales (>8 hours).

  18. Antidepressant-like effect of folic acid: Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway.

    PubMed

    Brocardo, Patrícia de Souza; Budni, Josiane; Lobato, Kelly Ribas; Kaster, Manuella Pinto; Rodrigues, Ana Lúcia S

    2008-11-19

    Antidepressant-like activity of folic acid in forced swimming test and in the tail suspension test was demonstrated previously by our group. In this study we investigated the involvement of N-methyl-d-aspartate (NMDA) receptors and l-arginine-nitric oxide (NO)-cyclic guanosine monophosphate pathway in its antidepressant-like effect in the forced swimming test in mice. The antidepressant-like effect of folic acid (10 nmol/site, i.c.v.) was prevented by the pretreatment of mice with NMDA (0.1 pmol/site, i.c.v.), l-arginine (750 mg/kg, i.p., substrate for nitric oxide synthase), S-nitroso-N-acetyl-penicillamine (SNAP, 25 microg/site, i.c.v, a NO donor) or sildenafil (5 mg/kg, i.p., phosphodiesterase 5 inhibitor). The administration of 7-nitroindazole (25 and 50 mg/kg, i.p., a specific neuronal nitric oxide synthase (nNOS) inhibitor) or methylene blue (20 mg/kg, i.p., direct inhibitor of both nitric oxide synthase and soluble guanylate cyclase) in combination with a sub-effective dose of folic acid (1 nmol/site, i.c.v.) reduced the immobility time in the FST as compared with either drug alone. Together the results suggest that the antidepressant-like effect of folic acid in the forced swimming test is dependent on an inhibition of either NMDA receptors or NO and cGMP synthesis.

  19. Effects of L-arginine pre-treatment in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s diseases in Balb/c mice

    PubMed Central

    Hami, Javad; Hosseini, Mehran; Shahi, Sekineh; Lotfi, Nassim; Talebi, Abolfazl; Afshar, Mohammad

    2015-01-01

    Background: Parkinson’s disease (PD) is a common neurodegenerative disease resulting from the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Increasing evidence demonstrated that mice treated intranasally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) suffered impairments in motor functions associated with disruption of DA neurons in SNc conceivably analogous to those observed in PD. L-arginine has been proposed as a novel neuroprotective agent that plays protective roles in several models of neuronal cellular damage. This study aimed to evaluate the effects of L-arginine on the numerical density of dark neurons (DNs) in the SNc of Balb/c mice subjected to MPTP administration. Methods: In the present study, we demonstrated that repeated treatment with L-arginine (300 mg/kg, i.p.) during 7 consecutive days attenuated the production of DNs in SNc of adult male Balb/c mice infused with a single intranasal administration of MPTP (1 mg/nostril). Results: Pre-treatment with L-arginine significantly decreased the numerical density of DNs in SNc of mice 21 days after intranasal MPTP administration. Conclusion: This investigation provides new insights in experimental models of PD, indicating that L-arginine represents a potential neuroprotective agent for the prevention of DA neuron degeneration in SNc observed in PD patients. PMID:26885338

  20. Characterisation of vitamin and mineral supplement users differentiated according to their motives for using supplements: results of the German National Nutrition Monitoring (NEMONIT).

    PubMed

    Frey, Anne; Hoffmann, Ingrid; Heuer, Thorsten

    2017-08-01

    To characterise German vitamin and mineral supplement users differentiated by their motives for supplement use. Data were obtained from the German National Nutrition Monitoring (2010/11) via two 24 h dietary recalls and a telephone interview. Motive-based subgroups of supplement users were identified by factor and cluster analysis. Sociodemographic, lifestyle, health and dietary characteristics and supplement use were examined. Differences were analysed using χ 2 tests, logistic and linear regression models. Germany, nationwide. Individuals (n 1589) aged 18-80 years. Three motive-based subgroups were identified: a 'Prevention' subgroup (n 324), characterised by the motive to prevent nutrient deficiencies; a 'Prevention and additional benefits' subgroup (n 166), characterised by motives to prevent health problems and improve well-being and performance; and a 'Treatment' subgroup (n 136), characterised by motives to treat nutrient deficiencies or diseases. Members of the two prevention subgroups had a higher Healthy Eating Index score and tended to be more physically active than non-users. Those in the 'Prevention and additional benefits' subgroup supplemented with a greater number of micronutrients. Members of the 'Treatment' subgroup tended to be older and have a lower self-reported health status than non-users, and supplemented with a smaller number of micronutrients. The majority of supplement users take supplements for preventive purposes and they are more health conscious than non-users of supplements due to their concerns about developing health problems. Those supplementing for treatment purposes may have underlying health indications and may be more likely to benefit from supplementation than those supplementing for preventive purposes.

  1. Pharmacokinetics of inorganic cobalt and a vitamin B12 supplement in the Thoroughbred horse: Differentiating cobalt abuse from supplementation.

    PubMed

    Hillyer, L L; Ridd, Z; Fenwick, S; Hincks, P; Paine, S W

    2018-05-01

    While cobalt is an essential micronutrient for vitamin B 12 synthesis in the horse, at supraphysiological concentrations, it has been shown to enhance performance in human subjects and rats, and there is evidence that its administration in high doses to horses poses a welfare threat. Animal sport regulators currently control cobalt abuse via international race day thresholds, but this work was initiated to explore means of potentially adding to application of those thresholds since cobalt may be present in physiological concentrations. To devise a scientific basis for differentiation between presence of cobalt from bona fide supplementation and cobalt doping through the use of ratios. Six Thoroughbred horses were given 10 mL vitamin B 12 /cobalt supplement (Hemo-15 ® ; Vetoquinol, Buckingham, Buckinghamshire, UK., 1.5 mg B 12 , 7 mg cobalt gluconate = 983 μg total Co) as an i.v. bolus then an i.v. infusion (15 min) of 100 mg cobalt chloride (45.39 mg Co) 6 weeks later. Pre-and post-administration plasma and urine samples were analysed for cobalt and vitamin B 12 . Urine and plasma samples were analysed for vitamin B 12 using an immunoassay and cobalt concentrations were measured via ICP-MS. Baseline concentrations of cobalt in urine and plasma for each horse were subtracted from their cobalt concentrations post-administration for the PK analysis. Compartmental analysis was used for the determination of plasma PK parameters for cobalt using commercially available software. On administration of a vitamin B 12 /cobalt supplement, the ratio of cobalt to vitamin B 12 in plasma rapidly increased to approximately 3 and then rapidly declined below a ratio of 1 and then back to near baseline over the next week. On administration of 100 mg cobalt chloride, the ratio initially exceeded 10 in plasma and then declined with the lower 95% confidence interval remaining above a ratio of 1 for 7 days. For two horses with extended sampling, the plasma ratio remained above one for

  2. Nutritional supplementation with arginine protects radiation-induced effects. An experimental study.

    PubMed

    Pinto, Flavia Cristina Morone; Campos-Silva, Pamella; Souza, Diogo Benchimol de; Costa, Waldemar Silva; Sampaio, Francisco José Barcellos

    2016-10-01

    To investigate the protective effect of L-arginine on the prostate (nonneoplasic) of rats with radiation-induced injury. Twenty-nine Wistar rats, male adult, allocated into three groups: Control group (C) was not exposed to irradiation (n=10); Radiated group (R) had undergone pelvic irradiation (n=10); Supplemented and radiated group (R+S) had undergone pelvic irradiation plus L-arginine supplementation (n=9). The animals were observed for signs of toxicity. After euthanization, the prostate was dissected under magnification and stained by hematoxylin and eosin to study acinar structures and stained with Picrosirius red for collagen analysis. After radiation exposure, all animals presented diarrhea, but supplementation with L-arginine reduced this effect. The weight gain in the R+S group was significantly higher than in the C and R groups. In the R+S group the collagen density and the prostate acinar area was similar to the R and C groups. Epithelial height was significantly reduced in group R compared with group C (p<0.0001). When comparing the group R+S with R, a statistical difference was observed to be present (p<0.0001). Pelvic radiation promotes systemic effects and some structural modifications in the ventral prostate of rats. These modifications can be prevented by oral supplementation with L-arginine.

  3. A novel mass spectrometry-based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l-arginine and l-citrulline optimized for LC-MS-TOF and LC-MS/MS.

    PubMed

    Wiśniewski, Jerzy; Fleszar, Mariusz G; Piechowicz, Joanna; Krzystek-Korpacka, Małgorzata; Chachaj, Angelika; Szuba, Andrzej; Lorenc-Kukula, Katarzyna; Masłowski, Leszek; Witkiewicz, Wojciech; Gamian, Andrzej

    2017-11-01

    Nitric oxide (NO) is a regulatory molecule involved in many biological processes. NO is produced by nitric oxide synthase by conversion of l-arginine to l-citrulline. l-Arginine methylated derivatives, asymmetric and symmetric dimethylarginines (asymmetric dimethylarginine, ADMA, and symmetric dimethylarginine, SDMA), regulate l-arginine availability and the activity of nitric oxide synthase. As such, they have been frequently investigated as potential biomarkers in pathologies associated with dysfunctions in NO synthesis. Here, we present a new multistep analytical methodology based on liquid chromatography combined with mass spectrometry for the accurate identification of l-arginine, l-citrulline, ADMA and SDMA. Compounds are measured as stable 2,3,4,5,6-pentafluorobenzoyl chloride derivatives, which allows for simultaneous analysis of all compounds through chromatographic separation of ADMA and SDMA using a reverse-phase column. Serum aliquots (100 μL) were spiked with isotope-labeled internal standards and sodium carbonate buffer. The derivatization process was carried out at 25°C for 10 minu using pentafluorobenzoyl chloride as derivatization reagent. Calibration demonstrated good linearity (R 2  = 0.9966-0.9986) for all derivatized compounds. Good accuracy (94.67-99.91%) and precision (1.92-11.8%) were observed for the quality control samples. The applicability of the method was evaluated in a cohort of angiological patients and healthy volunteers. The method discerned significantly lower l-arginine and l-citrulline in angiologic patients. This robust and fast LC-ESI-MS method may be a useful tool in quantitative analysis of l-arginine, ADMA, SDMA and l-citrulline. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Physiological consequences of starvation in Pseudomonas putida: degradation of intracellular protein and loss of activity of the inducible enzymes of L-arginine catabolism.

    PubMed

    Fan, C L; Rodwell, V W

    1975-12-01

    We investigated the degradation of radioisotopically labeled intracellular protein in starved, intact cells of Pseudomonas putida P2 (ATCC 25571) and the regulation of this process. Intracellular protein isotopically labeled with L-[4,5-3H]leucine during log-phase growth at 30 C is degraded at rates of 1 to 2%/h in log-phase cells and 7 to 9%/h in starved cells. Rifampin, chloramphenicol, and tosyllysine chloromethylketone lower the rate of protein degradation by starved cells. Addition to starved cells of a nutrient upon which the culture is induced for growth rapidly lowers the rate of protein degradation from 7 to 9%/h to less than 1.5%/h. A nutrient that is oxidized but that cannot immediately support growth also lowers the rate of starvation-induced protein degradation. Proteolytic activity of cell extracts requires a divalent metal ion and may be inhibited up to 60% by tosyllysine chloromethylketone or p-toluenesulfonyl fluoride. Rifampin and chloramphenicol have no effect. In contrast to intact cells, extracts of growing or starving cells degrade protein at equivalent rates. We also investigated the stabilities of the inducible transport system and of four inducible intracellular enzymes of L-arginine catabolism. These include: the membrane-associated, L-arginine-specific transport system; L-arginine oxidase (oxidase); alpha-ketoarginine decarboxylase (decarboxylase); gamma-guanidinobutyraldehyde dehydrogenase ( dehydrogenase); and gamma-guanidinobutyrate amidinohydrolase (hydrolase). In starved cells, the rates of loss of activities were: transport and dehydrogenase activities, stable; oxidase and decarboxylase activities, 20 to 30%/h; hydrolase activity, 5 to 8%/h. Chloramphenicol decreases the rate of loss of oxidase, decarboxylase, and hydrolase activity, whereas p-toluenesulfonyl fluoride lowers the rate of loss of decarboxylase but not of oxidase or hydrolase activity. Addition to starved cells of a nutrient for which they are already induced for

  5. Socioeconomic differentials in supplementation of vitamin A: evidence from the Philippines.

    PubMed

    Choi, Yoonjoung; Bishai, David; Hill, Kenneth

    2005-06-01

    The efficacy of supplementation of vitamin A in child survival has been well-demonstrated. However, the effectiveness of a programme of vitamin A supplementation at the population level has been rarely examined. Understanding how programmes reach disadvantaged children can help improve the design of initiatives of vitamin A supplementation. The differentials in receipt of vitamin A by socioeconomic status were assessed using data from the Philippines. Factors associated with receipt of vitamin A during the last six months were examined using the Philippines Demographic and Health Surveys conducted in 1993 and 1998. In total, 6,970 and 6,118 children aged 12-59 months were included in 1993 and 1998 respectively. Logistic regression was used for identifying associations between the outcome and the household socioeconomic variables. The coverage of national-level vitamin A supplementation increased from 27% in 1993 to 79% in 1998. However, children whose mothers did not complete primary education and children living in poor households were less likely to receive supplementation. This disparity increased between the surveys: the adjusted odds of vitamin A intake by poor households compared to middle-class households declined from 0.73 [95% confidence interval (CI) 0.61-0.87) in 1993 to 0.52 (95% CI 0.42-0.63)] in 1998, resulting in an increased health inequity. The vitamin A programme in the Philippines was not uniformly successful in reaching the most vulnerable children. Approaches targeting vulnerable households or approaches not requiring mothers to travel to distribution centres may be more promising.

  6. N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt, as an inactivator of hepatitis B surface antigen.

    PubMed Central

    Sugimoto, Y; Toyoshima, S

    1979-01-01

    N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt (CAE), exhibited a strong inactivating effect on hepatitis B surface antigen. Concentrations of CAE required for 50 and 100% inactivation of the antigen were 0.01 to 0.025% and 0.025 to 0.05% respectively. CAE completely inactivated hepatitis B surface antigen at the lowest concentration compared with various compounds including about 500 amino acid derivatives, sodium hypochlorite, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, and some detergents. Furthermore, CAE inactivated vaccinia virus, herpes simplex virus, and influenza virus, whereas poliovirus was not inactivated at all. The results suggest that the inactivating effects of CAE are related to interaction with lipid-containing viral envelopes. PMID:228595

  7. A novel method for the functionalization of aminoacids L-glycine, L-glutamic acid and L-arginine on maghemite/magnetite nanoparticles

    NASA Astrophysics Data System (ADS)

    Bruno, A. J.; Correa, J. R.; Peláez-Abellán, E.; Urones-Garrote, E.

    2018-06-01

    Nanoparticles of maghemite/magnetite functionalized with L-glycine, L-glutamic acid and L-arginine were synthesized by a novel method. The novel procedure consists in an alternative of that reported by Massart for the precipitation of magnetite in which the aminoacid is added in the carboxylate form. The amounts of aminoacid in the initial molar concentrations were 35%, 45% and 65% with respect to the ferrophase. The obtained nanoparticles were characterized by several techniques: X-ray diffraction (XRD), Fourier transform IR spectroscopy (FT-IR), transmission electron microscopy (TEM), Electron energy-loss spectroscopy (EELS) and magnetometry. The IR spectroscopy confirmed that the selected aminoacids were functionalized on the surface of iron oxide. XRD and EELS confirm that iron oxide consists of a maghemite-magnetite intermediate phase with an average particle size about 6 nm, which was measured by transmission electron microscopy. The superparamagnetic character of the nanoparticles was evaluated by magnetometry.

  8. Bulk growth of <001> organic nonlinear optical (NLO) L-arginine 4-nitrophenolate 4-nitrophenol dihydrate (LAPP) single crystals by SR method

    SciTech Connect

    Pandian, Muthu Senthil, E-mail: senthilpandianm@ssn.edu.in; Sivasubramani, V.; Ramasamy, P.

    2015-06-24

    A transparent uniaxial L-arginine 4-nitrophenolate 4-nitrophenol dehydrate (LAPP) single crystal having dimension of 20 mm diameter and 45 mm length was grown by Sankaranarayanan-Ramasamy (SR) method with a growth rate of 1 mm per day. Using an identical solution the conventional crystal grown to a dimension of 8×5×5 mm{sup 3} was obtained over a period of 30 days. The crystal structure has been confirmed by single crystal X-ray diffraction measurement. The crystalline perfection of LAPP crystals grown by slow evaporation solution technique (SEST) and SR method were characterized using Vickers microhardness, UV-Vis NIR, chemical etching, dark and photo current measurements. The above study indicatesmore » that the crystal quality of the Sankaranarayanan-Ramasamy (SR) method grown LAPP is good compared to the conventional method grown crystal.« less

  9. Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept-Study.

    PubMed

    Hafner, Patricia; Bonati, Ulrike; Erne, Beat; Schmid, Maurice; Rubino, Daniela; Pohlman, Urs; Peters, Thomas; Rutz, Erich; Frank, Stephan; Neuhaus, Cornelia; Deuster, Stefanie; Gloor, Monika; Bieri, Oliver; Fischmann, Arne; Sinnreich, Michael; Gueven, Nuri; Fischer, Dirk

    2016-01-01

    Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7–10 years were treated with L-arginine (3 x 2.5 g/d) and metformin (2 x 250 mg/d) for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post-treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients. ClinicalTrials.gov NCT02516085.

  10. Preparation of water soluble L-arginine capped CdSe/ZnS QDs and their interaction with synthetic DNA: Picosecond-resolved FRET study

    SciTech Connect

    Giri, Anupam; Goswami, Nirmal; Lemmens, Peter

    2012-08-15

    Graphical abstract: Förster resonance energy transfer (FRET) studies on the interaction of water soluble arginine-capped CdSe/ZnS QDs with ethidium bromide (EB) labeled synthetic dodecamer DNA. Highlights: ► We have solubilized CdSe/ZnS QD in water replacing their TOPO ligand by L-arginine. ► We have studied arginine@QD–DNA interaction using FRET technique. ► Arginine@QDs act as energy donor and ethidium bromide-DNA acts as energy acceptor. ► We have applied a kinetic model to understand the kinetics of energy transfer. ► Circular dichroism studies revealed negligible perturbation in the DNA B-form in the arg@QD-DNA complex. -- Abstract: We have exchanged TOPO (trioctylphosphine oxide) ligandmore » of CdSe/ZnS core/shell quantum dots (QDs) with an amino acid L-arginine (Arg) at the toluene/water interface and eventually rendered the QDs from toluene to aqueous phase. We have studied the interaction of the water soluble Arg-capped QDs (energy donor) with ethidium (EB) labeled synthetic dodecamer DNA (energy acceptor) using picoseconds resolved Förster resonance energy transfer (FRET) technique. Furthermore, we have applied a model developed by M. Tachiya to understand the kinetics of energy transfer and the distribution of acceptor (EB-DNA) molecules around the donor QDs. Circular dichroism (CD) studies revealed a negligible perturbation in the native B-form structure of the DNA upon interaction with Arg-capped QDs. The melting and the rehybridization pathways of the DNA attached to the QDs have been monitored by the CD which reveals hydrogen bonding is the associative mechanism for interaction between Arg-capped QDs and DNA.« less

  11. Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters

    PubMed Central

    Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Colas, Claire; Ucurum, Zöhre; Schlessinger, Avner; Fotiadis, Dimitrios

    2018-01-01

    The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures (Tms) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting Tms indicated stabilization of AdiC variants upon ligand binding, in which Tms and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family. PMID:29558430

  12. Effects of Mutations and Ligands on the Thermostability of the l-Arginine/Agmatine Antiporter AdiC and Deduced Insights into Ligand-Binding of Human l-Type Amino Acid Transporters.

    PubMed

    Ilgü, Hüseyin; Jeckelmann, Jean-Marc; Colas, Claire; Ucurum, Zöhre; Schlessinger, Avner; Fotiadis, Dimitrios

    2018-03-20

    The l-arginine/agmatine transporter AdiC is a prokaryotic member of the SLC7 family, which enables pathogenic enterobacteria to survive the extremely acidic gastric environment. Wild-type AdiC from Escherichia coli, as well as its previously reported point mutants N22A and S26A, were overexpressed homologously and purified to homogeneity. A size-exclusion chromatography-based thermostability assay was used to determine the melting temperatures ( T m s) of the purified AdiC variants in the absence and presence of the selected ligands l-arginine (Arg), agmatine, l-arginine methyl ester, and l-arginine amide. The resulting T m s indicated stabilization of AdiC variants upon ligand binding, in which T m s and ligand binding affinities correlated positively. Considering results from this and previous studies, we revisited the role of AdiC residue S26 in Arg binding and proposed interactions of the α-carboxylate group of Arg exclusively with amide groups of the AdiC backbone. In the context of substrate binding in the human SLC7 family member l-type amino acid transporter-1 (LAT1; SLC7A5), an analogous role of S66 in LAT1 to S26 in AdiC is discussed based on homology modeling and amino acid sequence analysis. Finally, we propose a binding mechanism for l-amino acid substrates to LATs from the SLC7 family.

  13. Intracellular acidification reduces l-arginine transport via system y+L but not via system y+/CATs and nitric oxide synthase activity in human umbilical vein endothelial cells.

    PubMed

    Ramírez, Marco A; Morales, Jorge; Cornejo, Marcelo; Blanco, Elias H; Mancilla-Sierpe, Edgardo; Toledo, Fernando; Beltrán, Ana R; Sobrevia, Luis

    2018-04-01

    l-Arginine is taken up via the cationic amino acid transporters (system y + /CATs) and system y + L in human umbilical vein endothelial cells (HUVECs). l-Arginine is the substrate for endothelial NO synthase (eNOS) which is activated by intracellular alkalization, but nothing is known regarding modulation of system y + /CATs and system y + L activity, and eNOS activity by the pHi in HUVECs. We studied whether an acidic pHi modulates l-arginine transport and eNOS activity in HUVECs. Cells loaded with a pH-sensitive probe were subjected to 0.1-20 mmol/L NH 4 Cl pulse assay to generate pHi 7.13-6.55. Before pHi started to recover, l-arginine transport (0-20 or 0-1000 μmol/L, 10 s, 37 °C) in the absence or presence of 200 μmol/L N-ethylmaleimide (NEM) (system y + /CATs inhibitor) or 2 mmol/L l-leucine (systemy + L substrate) was measured. Protein abundance for eNOS and serine 1177 or threonine 495 phosphorylated eNOS was determined. The results show that intracellular acidification reduced system y + L but not system y + /CATs mediated l-arginine maximal transport capacity due to reduced maximal velocity. Acidic pHi reduced NO synthesis and eNOS serine 1177 phosphorylation. Thus, system y + L activity is downregulated by an acidic pHi, a phenomenon that may result in reduced NO synthesis in HUVECs. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Effects of acute and chronic stress on the L-arginine nitric oxide pathway in black and white South Africans: the sympathetic activity and ambulatory blood pressure in Africans study.

    PubMed

    Reimann, Manja; Hamer, Mark; Malan, Nicolaas T; Schlaich, Markus P; Lambert, Gavin W; Ziemssen, Tjalf; Boeger, Rainer H; Malan, Leoné

    2013-10-01

    This study investigated the impact of stress on effectors of the L-arginine/nitric oxide (NO) system including the endogenous inhibitor asymmetric dimethylarginine (ADMA). Black (n = 168) and white (n = 206) South African teachers were exposed to a mental and a physical stressor for 1 minute, respectively. Serum samples for determination of l-arginine, NO metabolites, ADMA, and symmetric dimethylarginine (SDMA) were obtained at rest and during stress exposure. Perception of task stressfulness was assessed on a 7-point Likert scale, and psychological distress was estimated by the General Health Questionnaire. Black South Africans exhibited higher resting levels of NO metabolites (adjusted mean [standard error of the mean] = 11.3 [1.3] versus 3.9 [1.1] μmol/l, p < .001) but lower circulating ADMA (0.62 [0.02] versus 0.70 [0.02] μmol/l, p = .004) and SDMA (0.41 [0.01] versus 0.53 [0.01] μmol/l, p < .001) than did white South Africans. Ethnicity-by-psychological distress interaction was observed for resting levels of ADMA (p = .002), SDMA (p = .038), and L-arginine (p = .048). Ethnic differences in responses to experimental stress were evident for NO metabolites (blacks versus whites: 5.94 [1.55] versus -0.74 [1.25] μmol/l, p = .004) and SDMA (blacks versus whites: -0.02 [0.01] versus 0.02 [0.01] μmol/l, p = .004). Ethnicity-by-psychological distress interaction for stress responses was found for l-arginine/ADMA ratio (p = .027). The l-arginine/NO system is affected by psychosocial distress with higher susceptibility in black South Africans. This interaction may contribute to the higher cardiovascular disease risk in black South Africans.

  15. Duodenocutaneous fistula in rats as a model for "wound healing-therapy" in ulcer healing: the effect of pentadecapeptide BPC 157, L-nitro-arginine methyl ester and L-arginine.

    PubMed

    Skorjanec, S; Kokot, A; Drmic, D; Radic, B; Sever, M; Klicek, R; Kolenc, D; Zenko, A; Lovric Bencic, M; Belosic Halle, Z; Situm, A; Zivanovic Posilovic, G; Masnec, S; Suran, J; Aralica, G; Seiwerth, S; Sikiric, P

    2015-08-01

    While very rarely reported, duodenocutanenous fistula research might alter the duodenal ulcer disease background and therapy. Our research focused on rat duodenocutaneous fistulas, therapy, stable gastric pentadecapeptide BPC 157, an anti-ulcer peptide that healed other fistulas, nitric oxide synthase-substrate L-arginine, and nitric oxide synthase-inhibitor L-nitro-arginine methyl ester (L-NAME). The hypothesis was, duodenal ulcer-healing, like the skin ulcer, using the successful BPC 157, with nitric oxide-system involvement, the "wound healing-therapy", to heal the duodenal ulcer, the fistula-model that recently highlighted gastric and skin ulcer healing. Pressure in the lower esophageal and pyloric sphincters was simultaneously assessed. Duodenocutaneous fistula-rats received BPC 157 (10 μg/kg or 10 ng/kg, intraperitoneally or perorally (in drinking water)), L-NAME (5 mg/kg intraperitoneally), L-arginine (100 mg/kg intraperitoneally) alone and/or together, throughout 21 days. Duodenocutaneous fistula-rats maintained persistent defects, continuous fistula leakage, sphincter failure, mortality rate at 40% until the 4(th) day, all fully counteracted in all BPC 157-rats. The BPC 157-rats experienced rapidly improved complete presentation (maximal volume instilled already at 7(th) day). L-NAME further aggravated the duodenocutaneous fistula-course (mortality at 70% until the 4(th) day); L-arginine was beneficial (no mortality; however, maximal volume instilled not before 21(st) day). L-NAME-worsening was counteracted to the control level with the L-arginine effect, and vice versa, while BPC 157 annulled the L-NAME effects (L-NAME + L-arginine; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157 brought below the level of the control). It is likely that duodenocutaneous fistulas, duodenal/skin defect simultaneous healing, reinstated sphincter function, are a new nitric oxide-system related phenomenon. In conclusion, resolving the duodenocutanenous fistulashealing

  16. Class side effects: decreased pressure in the lower oesophageal and the pyloric sphincters after the administration of dopamine antagonists, neuroleptics, anti-emetics, L-NAME, pentadecapeptide BPC 157 and L-arginine.

    PubMed

    Belosic Halle, Zeljka; Vlainic, Josipa; Drmic, Domagoj; Strinic, Dean; Luetic, Kresimir; Sucic, Mario; Medvidovic-Grubisic, Maria; Pavelic Turudic, Tatjana; Petrovic, Igor; Seiwerth, Sven; Sikiric, Predrag

    2017-05-17

    The ulcerogenic potential of dopamine antagonists and L-NAME in rats provides unresolved issues of anti-emetic neuroleptic application in both patients and experimental studies. Therefore, in a 1-week study, we examined the pressures within the lower oesophageal and the pyloric sphincters in rats [assessed manometrically (cm H 2 O)] after dopamine neuroleptics/prokinetics, L-NAME, L-arginine and stable gastric pentadecapeptide BPC 157 were administered alone and/or in combination. Medication (/kg) was given once daily intraperitoneally throughout the 7 days, with the last dose at 24 h before pressure assessment. Given as individual agents to healthy rats, all dopamine antagonists (central [haloperidol (6.25 mg, 16 mg, 25 mg), fluphenazine (5 mg), levomepromazine (50 mg), chlorpromazine (10 mg), quetiapine (10 mg), olanzapine (5 mg), clozapine (100 mg), sulpiride (160 mg), metoclopramide (25 mg)) and peripheral(domperidone (10 mg)], L-NAME (5 mg) and L-arginine (100 mg) decreased the pressure within both sphincters. As a common effect, this decreased pressure was rescued, dose-dependently, by BPC 157 (10 µg, 10 ng) (also note that L-arginine and L-NAME given together antagonized each other's responses). With haloperidol, L-NAME worsened both the lower oesophageal and the pyloric sphincter pressure, while L-arginine ameliorated lower oesophageal sphincter but not pyloric sphincter pressure, and antagonized L-NAME effect. With domperidone, L-arginine originally had no effect, while L-NAME worsened pyloric sphincter pressure. This effect was opposed by L-arginine. All these effects were further reversed towards a stronger beneficial effect, close to normal pressure values, by the addition of BPC 157. In addition, NO level was determined in plasma, sphincters and brain tissue. Thiobarbituric acid reactive substances (TBARS) were also assessed. Haloperidol increased NO levels (in both sphincters, the plasma and brain), consistently producing increased

  17. Highly sensitive and simultaneous electrochemical determination of 2-aminophenol and 4-aminophenol based on poly(l-arginine)-β-cyclodextrin/carbon nanotubes@graphene nanoribbons modified electrode.

    PubMed

    Yi, Yinhui; Zhu, Gangbing; Wu, Xiangyang; Wang, Kun

    2016-03-15

    Owing to the similar characteristics and physiochemical property of 2-aminophenol (2-AP) and 4-aminophenol (4-AP), the highly sensitive simultaneous electrochemical determination of 2- and 4-AP is a great challenge. In this paper, by electropolymerizing β-cyclodextrin (β-CD) and l-arginine (l-Arg) on the surface of carbon nanotubes@graphene nanoribbons (CNTs@GNRs) core-shell heterostructure, a P-β-CD-l-Arg/CNTs@GNRs nanohybrid modified electrode was prepared successfully, and it could exhibit the synergetic effects of β-CD (high host-guest recognition and enrichment ability), l-Arg (excellent electrocatalytic activity) and CNTs@GNRs (prominent electrochemical properties and large surface area), the P-β-CD-l-Arg/CNTs@GNRs modified electrode was used in the electrochemical determination of 2- and 4-AP, the results demonstrated that the highly sensitive and simultaneous determination of 2- and 4-AP is successfully achieved and the modified electrode has a linear response range of 25.0-1300.0 nM for both 2- and 4-AP, and the detection limits of 2- and 4-AP obtained in this work are 6.2 and 3.5 nM, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Reversal effect of intra-central amygdala microinjection of L-arginine on place aversion induced by naloxone in morphine conditioned rats.

    PubMed

    Karimi, Sara; Karami, Manizheh; Sahraei, Hedayat; Rahimpour, Mahnaz

    2011-01-01

    Role of nitric oxide (NO) on expression of morphine conditioning using a solely classic task has been proposed previously. In this work, the involvement of NO on the expression of opioid-induced conditioning in the task paired with an injection of naloxone was investigated. Conditioning was established in adult male Wistar rats (weighing 200-250 g) using an unbiased procedure. Naloxone (0.05-0.4 mg/kg, i.p.), a selective antagonist of mu-opioid receptor, was administered once prior to morphine response testing. NO agents were administered directly into the central amygdala (CeA) prior to naloxone injection pre-testing. Morphine (2.5-10 mg/kg, s.c.) produced a significant dose-dependent place preference in experimental animals. When naloxone (0.05-0.4 mg/kg, i.p.) was injected before testing of morphine (5 mg/kg, s.c.) response, the antagonist induced a significant aversion. This response was reversed due to injection of L-arginine (0.3-3 microg/rat), intra-CeA prior to naloxone administration. However, pre-injection of L-NAME (intra-CeA), an inhibitor of NO production, blocked this effect. The finding may reflect that NO in the nucleus participates in morphine plus naloxone interaction.

  19. Do the accelerating actions of tianeptine and l-arginine on cortical spreading depression interact? An electrophysiological analysis in young and adult rats.

    PubMed

    Maia, Luciana Maria Silva de Seixas; Amancio-Dos-Santos, Angela; Germano, Paula Catirina Pereira da Silva; Falcão, Anna Carolina Santos Marinho; Duda-de-Oliveira, Desirré; Guedes, Rubem Carlos Araújo

    2017-05-22

    In the rat, we previously demonstrated that serotonin-enhancing drugs impair cortical spreading depression (CSD) and that l-arginine (arginine) treatment enhances CSD. Here, we investigated the interaction between topical application of the serotonin uptake enhancer tianeptine and systemic arginine administration on CSD. From postnatal day 7-28, female Wistar rats (n=40) received by gavage 300mg/Kg/day arginine (n=20) or water (n=20). Half of the arginine- or water-treated rats underwent CSD recording at 30-40days of age (young), while the other half was recorded at 90-120days (adult). Following baseline recording (four episodes of CSD), we applied tianeptine solution (10mg/ml) to a rectangular portion of the intact dura mater for 10-min and then elicited CSD. This procedure was repeated three times. Compared to baseline values, CSD velocities and amplitudes following tianeptine application increased, and CSD duration decreased significantly (p<0.05) in both young and adult rats, regardless of treatment group. CSD acceleration caused by systemic treatment with arginine is in agreement with previous findings. Topical cortical application of tianeptine replicated the effect of systemic application, suggesting a cortically based mechanism for tianeptine's action. However, the absence of interaction between arginine and tianeptine treatments suggests that they probably act through separate mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. INF-β1b therapy modulates L-arginine and nitric oxide metabolism in patients with relapse remittent multiple sclerosis.

    PubMed

    Stojanovic, Ivana; Vojinovic, Slobodan; Ljubisavljevic, Srdjan; Pavlovic, Radmila; Basic, Jelena; Pavlovic, Dusica; Ilic, Andjelka; Cvetkovic, Tatjana; Stukalov, Maja

    2012-12-15

    The scope of this study is the examination of NO(2)+NO(3), 3-nitrotyrosine (3-NT), S-nitrosothiols (RSNO), arginase activity and asymmetric (ADMA) and symmetric (SDMA) dimethyl-L-arginine concentrations in plasma of MS patients during interferon-β1b therapy. The study population included 15 (12 women, 3 men) untreated MS patients and 12 (10 women, 2 men) interferon-β1b treated MS patients with clinically definite relapsing MS (McDonalds criteria) for at least 1 year and a baseline EDSS score of 1.0 to 3.5 inclusive. Patients were treated with 250 μg IU interferon-β1b s.c. every second day during 30 months. The disease course was evaluated using correlations between baseline EDSS score and relapse rates in both groups. During interferon-β1b treatment, EDSS scores in treated patients were decreased compared to untreated ones - after 18 and 30 months (p<0.05). In interferon-β1b treated MS patients, NO(2)+NO(3), 3-NT and RSNO plasma concentrations were significantly lower (p<0.05), while arginase activity, ADMA and SDMA levels were significantly increased (p<0.05) during the therapy, compared to the baseline levels in treated patients. The investigated parameters may be the new biomarkers, providing information for the therapeutic approach and valuable in clinical monitoring. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. On the synthesis of tailored biomimetic hydroxyapatite nanoplates through a bioinspired approach in the presence of collagen or chitosan and L-arginine.

    PubMed

    Tsetsekou, A; Brasinika, D; Vaou, V; Chatzitheodoridis, E

    2014-10-01

    Controlling the structure of hydroxyapatite nanocrystals is vital for acquiring a consistent product. In an effort to synthesize crystals mimicking the morphology of natural bone's apatite, a bioinspired process was developed based on the use of a natural biomacromolecule, collagen or chitosan, in conjunction with l-arginine to direct the formation of hydroxyapatite from H3PO4 and Ca(OH)2. Different cases were investigated by employing various concentrations of the precursors and two molar ratios of Ca/P 1/1 and 10/6. The reaction was carried out at basic pH conditions and at biomimetic temperature (40°C). The resulting aqueous suspensions were characterized in terms of their rheological behavior, whereas the derived powders were fully evaluated by transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction analysis and Raman spectroscopy. The analysis showed that in all cases, the only phase detected was hydroxyapatite of a plate-like morphology very similar to that of natural apatite. The homogeneity of the morphology and the crystal size distribution depend on the precursors' final concentration with the mean size ranging from 5 nm up to 20 nm. The powder that demonstrated the best characteristics in terms of homogeneity was that produced in the presence of collagen for molar ratio of Ca/P 1/1. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Plasma Homocysteine and Asymmetrical Dimethyl-l-Arginine (ADMA) and Whole Blood DNA Methylation in Early and Neovascular Age-Related Macular Degeneration: A Pilot Study.

    PubMed

    Pinna, Antonio; Zinellu, Angelo; Tendas, Donatella; Blasetti, Francesco; Carru, Ciriaco; Castiglia, Paolo

    2016-01-01

    To compare the plasma levels of homocysteine and asymmetrical dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in patients with early and neovascular age-related macular degeneration (AMD) and in controls without maculopathy of any sort. This observational case-control pilot study included 39 early AMD patients, 27 neovascular AMD patients and 132 sex- and age-matched controls without maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole blood DNA methylation were measured. Quantitative variables were compared by Student's t-test or Mann-Whitney test. Logistic regression models were used to investigate the significance of the association between early or wet AMD and some variables. There were no significant differences in mean plasma homocysteine and ADMA concentrations and in the degree of whole blood DNA methylation between patients with early or neovascular AMD and their controls. Similarly, logistic regression analysis disclosed that plasma homocysteine and ADMA levels were not associated with an increased risk for early or neovascular AMD. We failed to demonstrate an association between early or neovascular AMD and increased plasma homocysteine and/or ADMA. Results also suggest that the degree of whole blood DNA methylation is not a marker of AMD.

  3. Virus activated artificial ECM induces the osteoblastic differentiation of mesenchymal stem cells without osteogenic supplements

    PubMed Central

    Wang, Jianglin; Wang, Lin; Li, Xin; Mao, Chuanbin

    2013-01-01

    Biochemical and topographical features of an artificial extracellular matrix (aECM) can direct stem cell fate. However, it is difficult to vary only the biochemical cues without changing nanotopography to study their unique role. We took advantage of two unique features of M13 phage, a non-toxic nanofiber-like virus, to generate a virus-activated aECM with constant ordered ridge/groove nanotopography but displaying different fibronectin-derived peptides (RGD, its synergy site PHSRN, and a combination of RGD and PHSRN). One feature is the self-assembly of phage into a ridge/groove structure, another is the ease of genetically surface-displaying a peptide. We found that the unique ridge/groove nanotopography and the display of RGD and PHSRN could induce the osteoblastic differentiation of mesenchymal stem cells (MSCs) without any osteogenic supplements. The aECM formed through self-assembly and genetic engineering of phage can be used to understand the role of peptide cues in directing stem cell behavior while keeping nanotopography constant. PMID:23393624

  4. Chronic N(G)-nitro-L-arginine methyl ester-induced hypertension : novel molecular adaptation to systolic load in absence of hypertrophy

    NASA Technical Reports Server (NTRS)

    Bartunek, J.; Weinberg, E. O.; Tajima, M.; Rohrbach, S.; Katz, S. E.; Douglas, P. S.; Lorell, B. H.; Schneider, M. (Principal Investigator)

    2000-01-01

    BACKGROUND: Chronic N(G)-nitro-L-arginine methyl ester (L-NAME), which inhibits nitric oxide synthesis, causes hypertension and would therefore be expected to induce robust cardiac hypertrophy. However, L-NAME has negative metabolic effects on protein synthesis that suppress the increase in left ventricular (LV) mass in response to sustained pressure overload. In the present study, we used L-NAME-induced hypertension to test the hypothesis that adaptation to pressure overload occurs even when hypertrophy is suppressed. METHODS AND RESULTS: Male rats received L-NAME (50 mg. kg(-1). d(-1)) or no drug for 6 weeks. Rats with L-NAME-induced hypertension had levels of systolic wall stress similar to those of rats with aortic stenosis (85+/-19 versus 92+/-16 kdyne/cm). Rats with aortic stenosis developed a nearly 2-fold increase in LV mass compared with controls. In contrast, in the L-NAME rats, no increase in LV mass (1. 00+/-0.03 versus 1.04+/-0.04 g) or hypertrophy of isolated myocytes occurred (3586+/-129 versus 3756+/-135 microm(2)) compared with controls. Nevertheless, chronic pressure overload was not accompanied by the development of heart failure. LV systolic performance was maintained by mechanisms of concentric remodeling (decrease of in vivo LV chamber dimension relative to wall thickness) and augmented myocardial calcium-dependent contractile reserve associated with preserved expression of alpha- and beta-myosin heavy chain isoforms and sarcoplasmic reticulum Ca(2+) ATPase (SERCA-2). CONCLUSIONS: When the expected compensatory hypertrophic response is suppressed during L-NAME-induced hypertension, severe chronic pressure overload is associated with a successful adaptation to maintain systolic performance; this adaptation depends on both LV remodeling and enhanced contractility in response to calcium.

  5. Chronic hypoxia decreases arterial and venous compliance in isolated perfused rat lungs: an effect that is reversed by exogenous l-arginine

    PubMed Central

    Jin, Yi; Chen, Bernadette; Calvert, Thomas J.; Chicoine, Louis G.; Liu, Yusen

    2013-01-01

    Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance (Ca) in right ventricular work, a decrease in Ca would add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases from l-arginine (l-Arg). However, little is known of the effect of l-Arg on vascular compliance (Cv) in the lung. We hypothesized that exposure to CH would decrease Ca and that this effect would be reversed by exogenous l-Arg. Sprague-Dawley rats were exposed to either normoxia or CH for 14 days; the lungs were then isolated and perfused. Vascular occlusions were performed and modeled using a three-compliance, two-resistor model. Pressure-flow curves were generated, and a distensible vessel model was used to estimate distensibility and a vascular resistance parameter (R0). Hypoxia resulted in the expected increase in arterial resistance (Ra) as well as a decrease in both Ca and Cv. l-Arg had little effect on Ra, Ca, or Cv in isolated lungs from normoxic animals. l-Arg decreased Ra in lungs from CH rats and redistributed compliance to approximately that found in normoxic lungs. CH increased R0, and l-Arg reversed this increase in R0. l-Arg increased exhaled NO, and inhibition of l-Arg uptake attenuated the l-Arg-induced increase in exhaled NO. These data demonstrate that the CH-induced decrease in Ca was reversed by l-Arg, suggesting that l-Arg may improve CH-induced right ventricular dysfunction. PMID:23103497

  6. Vascular and antioxidant effects of an aqueous Mentha cordifolia extract in experimental N(G)-nitro-L-arginine methyl ester-induced hypertension.

    PubMed

    Pakdeechote, Poungrat; Prachaney, Parichat; Berkban, Warinee; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Khrisanapant, Wilaiwan; Phirawatthakul, Yada

    2014-01-01

    The effect of an aqueous Mentha cordifolia (MC) extract on the haemodynamic status, vascular remodeling, function, and oxidative status in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertension was investigated. Male Sprague-Dawley rats were given L-NAME [50 mg/(kg body weight (BW) d)] in their drinking water for 5 weeks and were treated by intragastric administration with the MC extract [200 mg/(kgBWd)] for 2 consecutive weeks. Quercetin [25 mg/(kg BW d)] was used as a positive control. The effects of the MC extract on the haemodynamic status, thoracic aortic wall thickness, and oxidative stress markers were determined, and the vasorelaxant activity of the MC extract was tested in isolated mesenteric vascular beds in rats. Significant increases in the mean arterial pressure (MAP), heart rate (HR), hind limb vascular resistance (HVR), wall thickness, and cross-sectional area of the thoracic aorta, as well as oxidative stress markers were found in the L-NAME-treated group compared to the control (P < 0.05). MAP, HVR, wall thickness, cross-sectional area of the thoracic aorta, plasma malondialdehyde (MDA), and vascular superoxide anion production were significantly reduced in L-NAME hypersensitive rats treated with the MC extract or quercetin. Furthermore, the MC extract induced vasorelaxation in the pre-constricted mesenteric vascular bed with intact and denuded endothelium of normotensive and hypertensive rats. Our results suggest that the MC extract exhibits an antihypertensive effect via its antioxidant capacity, vasodilator property, and reduced vascular remodeling.

  7. Involvement of NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test.

    PubMed

    Ostadhadi, Sattar; Khan, Muhammad Imran; Norouzi-Javidan, Abbas; Chamanara, Mohsen; Jazaeri, Farahnaz; Zolfaghari, Samira; Dehpour, Ahmad-Reza

    2016-04-01

    Topiramate (TPM) is an agent primarily used in the treatment of epilepsy. Using mice model of forced swimming test (FST) the current study was basically aimed to investigate the influence of TPM on depression by inhibiting NMDA receptor and nitric oxide-cGMP production. When TPM was administered in a dose of 20 and 30 mg/kg by i.p. route it reduced the immobility time during FST. However this effect of TPM (30 mg/kg, i.p.) in the FST was abolished when the mice were pretreated either with NMDA (75 mg/kg, i.p.), or l-arginine (750 mg/kg, i.p. NO precursor), or sildenafil (5mg/kg, i.p. Phosphodiesterase 5 inhibitor). The immobility time in the FST was reduced after administration of L-NAME (10mg/kg, i.p, a non-specific NOS inhibitor), 7-nitoinidazol (30 mg/kg, i.p. a nNOS inhibitor) or MK-801 (0.05 mg/kg, i.p, a NMDA receptor antagonist) in combination with a subeffective dose of TPM (10mg/kg, i.p.) as compared with single use of either drug. Co-administrated of lower doses of MK-801 (0.01 mg/kg) or L-NAME (1mg/kg) failed to effect immobility time. However, simultaneous administration of these two agents in the same doses with subeffective dose of TPM (10mg/kg, i.p.), reduced the immobility time during FST. None of these drugs were found to have a profound effect on the locomotor activity per se during the open field test. Taken together, our data demonstrates that TPM exhibit antidepressant-like effect which is accomplished either due to inhibition of NMDA receptors or NO-cGMP production. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Effect of N(G)-nitro-L-arginine methyl ester on intestinal permeability following intestinal ischemia-reperfusion injury in a rat model.

    PubMed

    Luo, C C; Chen, H M; Chiu, C H; Lin, J N; Chen, J C

    2001-07-01

    Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase in intestinal permeability in rats following IRI. Sprague-Dawley rats weighing 200-300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early N(G)-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI. Copyright 2001 S. Karger AG, Basel

  9. In ovo feeding of l-arginine regulates intestinal barrier functions of posthatch broilers by activating the mTOR signaling pathway.

    PubMed

    Gao, Tian; Zhao, Minmeng; Zhang, Lin; Li, Jiaolong; Yu, Lanlin; Gao, Feng; Zhou, Guanghong

    2018-03-01

    During the last phase of incubation, dramatic physiological and metabolic changes occur in chick embryos, and supplies of nutrients and energy are always insufficient. This study investigated the effects of in ovo feeding (IOF) of l-arginine (Arg) on the hatchability, growth performance, intestinal development and functions of posthatch broilers. The IOF of Arg increased (P < 0.05) the feed intake and body weight gain during 1-21 days and 1-42 days, and the intestinal weight of 7- and 21-day-old broilers, compared with non-injected control and diluent-injected groups. The IOF of Arg increased (P < 0.05) villus height (VH), ratio of VH to crypt depth (CD) and density of goblet cells, and decreased (P < 0.05) the CD in jejunum of 1-, 7- and 21-day-old broilers. The IOF of Arg also increased (P < 0.05) the percentage of proliferating cell nuclear antigen positive cells of villus, and the mRNA expressions of mucin-2, claudin-1, zonula occludens-1 and -2 in jejunal mucosa of 21-day-old broilers. Meanwhile, IOF of Arg increased (P < 0.05) the protein abundance of phosphorylated mechanistic target of rapamycin (mTOR), ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E binding protein 1 in jejunal mucosa. The IOF of Arg improved the development and barrier functions of small intestine, which might be associated with activating the mTOR pathway. In addition, the improved intestinal development might explain the improvement in feed intake and consequently the growth performance of broilers. Therefore, IOF of Arg solution could be an effective technology for regulating early nutrition supply and subsequent growth development in the poultry industry. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  10. The effect of hypocaloric diet enriched in legumes with or without L-arginine and selenium on anthropometric measures in central obese women

    PubMed Central

    Alizadeh, Mohammad; Daneghian, Sevana; Ghaffari, Aida; Ostadrahimi, Alireza; Safaeiyan, Abdolrasoul; Estakhri, Rassul; Gargari, Bahram Pourghasem

    2010-01-01

    BACKGROUND: Identifying new ways to decrease adiposity will be very valuable for health. The aim of this study was to find out whether L-Arginine (Arg) and selenium alone or together can increase the effect of hypocaloric diet enriched in legumes (HDEL) on anthropometric measures in healthy obese women. METHODS: This randomized, double-blind, placebo-controlled trial was undertaken in 84 healthy premenopausal women with central obesity. After 2 weeks of run-in on an isocaloric diet, participants were randomly considered to eat HDEL, Arg (5 g/d) and HDEL, selenium (200 µg/d) and HDEL or Arg, selenium and HDEL for 6 weeks. The following variables were assessed before intervention and 3 and 6 weeks after it: weight, waist circumference, hip circumference, waist to hip ratio (WHR), body mass index (BMI), and fasting nitrite/nitrate (NOx) concentrations. Other variables (arm, thigh, calf and breast circumferences, subscapular, triceps, biceps and suprailiac skinfold thicknesses, sum of skinfold thicknesses (SSF), body density (D) and estimated percent of body fat (EPF)) were assessed before and after intervention. RESULTS: HDEL showed a significant effect in reduction of waist, hip, arm, thigh, calf and breast circumferences, triceps, biceps, subscapular and suprailiac skinfold thicknesses, WHR, SSF, D and EPF. HDEL + Arg + selenium significantly reduced suprailiac skinfold thicknesses; and there was no significant effect of HDEL, Arg, selenium and Arg plus selenium on weight, BMI and fasting NOx. CONCLUSIONS: The study indicates that HDEL + Arg + selenium reduce suprailiac skinfold thicknesses which represents the abdominal obesity reduction. PMID:21526106

  11. Diagnostic significance of nitrates and nitrites and L-arginine, in development of hepatorenal syndrome in patients with end stage alcoholic liver cirrhosis.

    PubMed

    Nickovic, Vanja; Kocic, Gordana; Bjelakovic, Goran; Pavlovic, Radmila; Stojanovic, Ivana; Katanic, Radoslav; Stojanovic, Svetlana; Djindjic, Boris

    2013-01-01

    Hepatorenal syndrome (HRS) represents a complication of the end-stage liver cirrhosis. The aim of the present study was to analyze concentrations of nitrates and nitrites (NO2 + NO3) and L-arginine in patients with liver cirrhosis and HRS as a possible predictive marker for the development of HRS. The research was performed in a group of 28 patients with cirrhosis and HRS, a group of 22 patients suffering from cirrhosis without HRS and a control group comprised of 42 healthy voluntary blood donors. In patients with end-stage alcoholic liver cirrhosis, with HRS, the concentrations of NO2 + NO3 increased and correlated with the degree of cirrhosis progression, compared to patients without HRS and significantly higher compared to the control group. The level of NO2 + NO3 was in a positive correlation with the degree of liver damage de Ritis coefficient (HRS = 0.72; cirrhosis: = 0.55; control = -0.10). Significant positive correlation was found between NO2 + NO3 concentration and inflammatory marker C-reactive protein (HRSC = 0.75; cirrhosis = 0.70, control = -0.25). The correlation between NO2 + NO3 concentration and creatinine concentration in patients with HRS was significantly higher compared to patients without HRS (HRS = 0.82; cirrhosis = 0.32; control = -0.25). By using binary regression analysis, on the basis of clinical criteria of HRS diagnosis, the strongest independent positive predictor for HRS development was NO2 + NO3, associated with 45.02 times higher incidence of HRS, compared to arginine (12.7 times higher incidence), creatinine (13.1 times higher incidence), and AST/ALT ratio (10.55 higher incidence of HRS). Since the determination of NO2 + NO3 represents a reliable and easily applicable method, it may be used as an early predictive marker for HRS development.

  12. Melatonin prevents fibrosis but not hypertrophy development in the left ventricle of NG-nitro-L-arginine-methyl ester hypertensive rats.

    PubMed

    Paulis, Ludovit; Pechanova, Olga; Zicha, Josef; Krajcirovicova, Kristina; Barta, Andrej; Pelouch, Vaclav; Adamcova, Michaela; Simko, Fedor

    2009-08-01

    Melatonin was shown to reduce blood pressure, enhance nitric oxide availability and scavenge free radicals. There is, however, a shortage of data with respect to the effect of melatonin on pathological left ventricular remodelling associated with haemodynamic overload. We investigated whether melatonin was able to prevent left ventricular hypertrophy (LVH) and fibrosis associated with N(G)-nitro-L-arginine-methyl ester (L-NAME)-induced hypertension. Four groups of male Wistar rats were investigated: control, L-NAME (50 mg/kg per day), melatonin (10 mg/kg per day) and L-NAME plus melatonin. Blood pressure was measured non-invasively each week. After 5 weeks of treatment the animals were killed and nitric oxide synthase (NOS) activity, endothelial and inducible NOS expression, the level of collagenous proteins, hydroxyproline and conjugated dienes in the left ventricle were determined. The administration of L-NAME inhibited NOS activity, increased conjugated dienes concentration, elevated blood pressure and induced LVH and fibrosis (indicated by increased collagenous proteins and hydroxyproline levels). The addition of melatonin to L-NAME treatment failed to prevent the attenuation of NOS activity and the development of LVH and prevented hypertension only partly. The administration of melatonin, however, completely prevented the increase in conjugated dienes concentration and the development of left ventricular fibrosis. NOS expression was not different among experimental groups. Melatonin prevented the development of left ventricular fibrosis and the increase in oxidative load in rats with L-NAME-induced hypertension. The antifibrotic effect of melatonin seems to be independent of its effects on NOS activity and might be linked to its antioxidant properties.

  13. Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice.

    PubMed

    Rajapakse, Niwanthi W; Karim, Florian; Evans, Roger G; Kaye, David M; Head, Geoffrey A

    2015-01-01

    Augmenting endothelial specific transport of the nitric oxide precursor L-arginine via cationic amino acid transporter-1 (CAT1) can prevent obesity related hypertension. We tested the hypotheses that CAT1 overexpression prevents obesity-induced hypertension by buffering the influence of the sympathetic nervous system (SNS) on the maintenance of arterial pressure and by buffering pressor responses to stress. Wild type (WT; n=13) and CAT1 overexpressing mice (CAT+; n=13) were fed a normal or a high fat diet for 20 weeks. Mice fed a high fat diet were returned to the control diet before experiments commenced. Baseline mean arterial pressure (MAP) and effects of restraint-, shaker- and almond feeding-stress and ganglionic blockade (pentolinium; 5 mg/kg; i.p.) on MAP were determined in conscious mice. Fat feeding increased body weight to a similar extent in WT and CAT+ but MAP was greater only in WT compared to appropriate controls (by 29%). The depressor response to pentolinium was 65% greater in obese WT than lean WT (P < 0.001), but was similar in obese and lean CAT+ (P = 0.65). In lean WT and CAT+, pressor responses to shaker and feeding stress, but not restraint stress, were less in the latter genotype compared to the former (P ≤ 0.001). Pressor responses to shaker and feeding stress were less in obese WT than lean WT (P ≤ 0.001), but similar in obese and lean CAT+. The increase in MAP in response to restraint stress was less in obese WT (22 ± 2%), but greater in obese CAT+ (37 ± 2%), when compared to respective lean WT (31 ± 3%) and lean CAT+ controls (27 ± 2%; P ≤ 0.02). We conclude that CAT1 overexpression prevents obesity-induced hypertension by reducing the influence of the SNS on the maintenance of arterial pressure but not by buffering pressor responses to stress.

  14. Electron Transfer Dissociation with Supplemental Activation to Differentiate Aspartic and Isoaspartic Residues in Doubly Charged Peptide Cations

    PubMed Central

    Chan, Wai Yi Kelly; Chan, T. W. Dominic; O’Connor, Peter B.

    2011-01-01

    Electron-transfer dissociation (ETD) with supplemental activation of the doubly charged deamidated tryptic digested peptide ions allows differentiation of isoaspartic acid and aspartic acid residues using c + 57 or z• − 57 peaks. The diagnostic peak clearly localizes and characterizes the isoaspartic acid residue. Supplemental activation in ETD of the doubly charged peptide ions involves resonant excitation of the charge reduced precursor radical cations and leads to further dissociation, including extra backbone cleavages and secondary fragmentation. Supplemental activation is essential to obtain a high quality ETD spectrum (especially for doubly charged peptide ions) with sequence information. Unfortunately, the low-resolution of the ion trap mass spectrometer makes detection of the diagnostic peak for the aspartic acid residue difficult due to interference with side-chain loss from arginine and glutamic acid residues. PMID:20304674

  15. Inhibition of adipogenic differentiation by myostatin is alleviated by arginine supplementation in porcine-muscle-derived mesenchymal stem cells.

    PubMed

    Lei, Hulong; Yu, Bing; Yang, Xuerong; Liu, Zehui; Huang, Zhiqing; Mao, Xiangbing; Tian, Gang; He, Jun; Han, Guoquan; Chen, Hong; Mao, Qian; Chen, Daiwen

    2011-10-01

    Porcine mesenchymal stem cells in postnatal muscle have been demonstrated to differentiate into adipocytes. This increases adipocyte number and lipid accumulation, and is thought to be the origin of intramuscular fat. In this study, the effects of myostatin and arginine on adipogenic differentiation in mesenchymal stem cells derived from porcine muscle (pMDSCs) were investigated in vitro. Intracellular triglyceride levels were reduced by exogenous myostatin and increased by arginine supplementation or myostatin antibody (P<0.01). The inhibition of lipid accumulation by myostatin in pMDSCs was alleviated by arginine supplementation (P<0.01). Expression patterns of adipogenic transcription factors showed that exogenous myostatin suppressed PPARγ2 and aP2 expression (P<0.01), while supplemental arginine or myostatin antibody promoted ADD1 expression (P<0.01). Furthermore, compared with the addition of either myostatin protein or antibody alone, ADD1 and PPARδ expression were promoted by the combination of arginine and myostatin (P<0.01), and arginine combined with myostatin antibody promoted the expression of ADD1, PPARδ, C/EBPα, PPARγ2 and LPL in pMDSCs (P<0.05). These results suggest that myostatin inhibits adipogenesis in pMDSCs, and that this can be alleviated by arginine supplementation, at least in part, through promoting ADD1 and PPARδ expression.

  16. Simple low cost differentiation of Candida auris from Candida haemulonii complex using CHROMagar Candida medium supplemented with Pal's medium.

    PubMed

    Kumar, Anil; Sachu, Arun; Mohan, Karthika; Vinod, Vivek; Dinesh, Kavitha; Karim, Shamsul

    Candida auris is unique due to its multidrug resistance and misidentification as Candida haemulonii by commercial systems. Its correct identification is important to avoid inappropriate treatments. To develop a cheap method for differentiating C. auris from isolates identified as C. haemulonii by VITEK2. Fifteen C. auris isolates, six isolates each of C. haemulonii and Candida duobushaemulonii, and one isolate of Candida haemulonii var. vulnera were tested using CHROMagar Candida medium supplemented with Pal's agar for better differentiation. On CHROMagar Candida medium supplemented with Pal's agar all C. auris strains showed confluent growth of white to cream colored smooth colonies at 37°C and 42°C after 24 and 48h incubation and did not produce pseudohyphae. The isolates of the C. haemulonii complex, on the contrary, showed poor growth of smooth, light-pink colonies at 24h while at 48h the growth was semiconfluent with the production of pseudohyphae. C. haemulonii complex failed to grow at 42°C. We report a rapid and cheap method using CHROMagar Candida medium supplemented with Pal's agar for differentiating C. auris from isolates identified as C. haemulonii by VITEK2. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Effects of aqueous leaf extract of Tridax procumbens on contractile activity of corpus cavernosum in N-nitro-l-arginine methyl ester-induced hypertensive male rats.

    PubMed

    Salami, Shakiru Ademola; Salahdeen, Hussein Mofomosara; Ugbebor, Evangelshane Chukwudubem; Murtala, Babatunde Adekunle; Raji, Yinusa

    2018-01-01

    This study investigated the effects of aqueous leaf extract of Tridax procumbens (ALETP) on contractile activity of corpus cavernosum in N-nitro-l-arginine methyl ester (l-NAME)-induced hypertensive male rats. Twenty normal, adult male rats (130-150 g) were divided into four groups of five rats each. Group I (control) was given normal saline (0.6 mL/kg) and group II was given l-NAME (40 mg/kg) for 6 weeks. Groups III and IV also received l-NAME (40 mg/kg) for 6 weeks but were further co-treated with 100 and 200 mg/kg of ALETP, respectively, from week 4 to week 6. All treatments were given orally. Strips of corpus cavernosum from each of the four groups were exposed to increasing concentrations of acetylcholine (ACh) and sodium nitroprusside (SNP) (10 -9 -10 -5 mol/L) after contraction with phenylephrine (10 -7  mol/L) to test for a dose-response effect. Response to potassium and calcium was also measured after cumulatively adding potassium and calcium (10-50 mmol/L) to potassium- and calcium-free organ chamber. Isometric contractions were recorded through an Ugo Basile data capsule acquisition system. Mean arterial blood pressure was significantly reduced in the ALETP co-treated group compared to the control and l-NAME-only groups (P < 0.05). Cavernosa strips from ALETP co-treated rats exhibited significant inhibition of contraction in response to phenylephrine, potassium chloride, and calcium chloride (P < 0.05). Relaxation in response to Ach and SNP was also significantly impaired in cavernosa strips from the l-NAME-only treated group (P < 0.05), while ALETP co-treated groups showed enhanced percentage relaxation. ALETP treatment of l-NAME-induced hypertensive rats promotes a relaxant effect on isolated cavernosa strips. ALETP shows potential in correcting erectile dysfunction in hypertension. Copyright © 2017 Shanghai Changhai Hospital. Published by Elsevier B.V. All rights reserved.

  18. Effects of in ovo feeding of l-arginine on breast muscle growth and protein deposition in post-hatch broilers.

    PubMed

    Yu, L L; Gao, T; Zhao, M M; Lv, P A; Zhang, L; Li, J L; Jiang, Y; Gao, F; Zhou, G H

    2018-02-26

    In ovo feeding (IOF) of l-arginine (Arg) can affect growth performance of broilers, but the response of IOF of Arg on breast muscle growth is unclear, and the mechanism involved in protein deposition remains unknown. Hense, this experiment was conducted to evaluate the effects of IOF of Arg on breast muscle growth and protein-deposited signalling in post-hatch broilers. A total of 720 fertile eggs were collected from 34-week-old Arbor Acres breeder hens and distributed to three treatments: (1) non-injected control group; (2) 7.5 g/l (w/v) NaCl diluent-injected control group; (3) 0.6 mg Arg/egg solution-injected group. At 17.5 days of incubation, fertile eggs were injected 0.6 ml solutions into the amnion of the injected groups. Upon hatching, 80 male chicks were randomly assigned to eight replicates of 10 birds each and fed ad libitum for 21 days. The results indicated that IOF of Arg increased relative breast muscle weight compared with those of control groups at hatch, 3-, 7- and 21-day post-hatch (P<0.05). In the Arg-injected group, the plasma total protein and albumen concentrations were higher at 7- and 21-day post-hatch than those of control groups (P<0.05). The alanine aminotransferase activity in Arg group was higher at hatch than that of control groups (P<0.05). The levels of triiodothyronine at four time points and thyroxine hormones at hatch, 7- and 21-day post-hatch in Arg group were higher than those of control groups (P<0.05). In addition, IOF of Arg increased the amino acid concentrations of breast muscle at hatch, 7- and 21-day post-hatch (P<0.05). In ovo feeding of Arg also enhanced mammalian target of rapamycin, ribosomal protein S6 kinase-1 and eIF4E-bindingprotein-1 messenger RNA expression levels at hatch compared with those of control groups (P<0.05). It was concluded that IOF of Arg treatment improved breast muscle growth, which might be associated with the enhancement of protein deposition.

  19. Effects of in ovo feeding of L-arginine on the development of digestive organs, intestinal function and post-hatch performance of broiler embryos and hatchlings.

    PubMed

    Gao, T; Zhao, M M; Li, Y J; Zhang, L; Li, J L; Yu, L L; Gao, F; Zhou, G H

    2018-02-01

    This study was to investigate the effects of in ovo feeding (IOF) L-arginine (Arg) solution on the development of digestive organs, the duodenal mucosa of broiler embryos and hatchlings, and the growth performance of chicks during the first week post-hatch. A total of 720 fertilized eggs with similar weight were randomly allocated to three groups, consisting of eight replicates of 30 eggs each. Three treatments were arranged as non-injected control, diluent-injected (0.75% NaCl solution) group and Arg solution-injected group containing 1% Arg, dissolved in diluent. At 17.5 days of incubation, 0.6 ml of IOF solution was injected into amniotic fluid of each egg of injected groups. Results showed IOF of Arg solution increased (p < .05) the chick embryo weight at 19 days of incubation; the body weight gain of post-hatch broilers during 1-7 days; the weights of liver, pancreas, proventriculus and gizzard; the concentrations of duodenal ghrelin, vasoactive intestinal peptide and glucagon-like peptide 2; and the duodenum mucosal enzyme activities of alkaline phosphatase, maltase, sucrase and inducible nitric oxide synthase of 7-day-old post-hatch broilers compared with other groups. The IOF of Arg solution also increased (p < .05) the villus height (VH) and the ratio of VH to crypt depth (CD) and decreased (p < .05) the CD in duodenum of broiler embryos and post-hatch hatchlings, except for the CD at 19 days of incubation. In conclusion, IOF of 1% Arg solution into the amnion at 17.5 days of incubation could improve the development of digestive organs, the duodenal morphology, the releasing of gastrointestinal hormones and mucosal enzyme activities of broiler embryos and hatchlings and finally the growth performance of chicks during the first week post-hatch. Therefore, IOF of appropriate Arg solution could be an effective technology for regulating early nutrition supply and subsequent growth development in poultry industry. © 2017 Blackwell Verlag GmbH.

  20. Effect of nitro-L-arginine on electrical and mechanical responses to acetylcholine in the superior mesenteric artery from stroke-prone hypertensive rat

    PubMed Central

    Ghisdal, Philippe; Godfraind, Théophile; Morel, Nicole

    1999-01-01

    High salt diet is known to aggravate the vascular pathology in spontaneously hypertensive stroke-prone rats (SHR-SP). The aim of the present study was to assess the involvement of endothelial dysfunction in this effect. Contractile tension and membrane potential were simultaneously recorded in superior mesenteric artery rings of untreated and NaCl-loaded (1% NaCl in the drinking water) SHR-SP and normotensive Wistar Kyoto rats (WKY).In unstimulated artery, hyperpolarization evoked by acetylcholine was not different in WKY and in NaCl-loaded WKY; it was reduced in SHR-SP and further reduced in NaCl-loaded SHR-SP. Hyperpolarization was unaffected by Nω-nitro-L-arginine (L-NA) but was abolished in high-KCl solution.In noradrenaline-stimulated artery, ACh-evoked hyperpolarization and relaxation were not different in WKY and in SHR-SP. NaCl-treatment did not affect the responses to ACh in WKY but decreased maximum relaxation in SHR-SP from 93±2% to 72±7% of the contraction. In WKY, in NaCl-loaded WKY and in SHR-SP, L-NA similarly shifted the concentration-relaxation curve to ACh to the right and depressed its maximum but L-NA did not affect the hyperpolarization to ACh. In NaCl-loaded SHR-SP, L-NA blunted the effects of ACh on membrane potential and on contraction.The NO donor SNAP abolished the depolarization and the contraction evoked by noradrenaline with the same potency in WKY and in untreated SHR-SP but was more potent in NaCl-loaded SHR-SP.In KCl-contracted arteries the relaxations to ACh were not different in WKY and SHR-SP but NaCl-loaded SHR-SP were more sensitive to ACh.The results showed that NaCl-rich diet markedly reduced the L-NA-resistant responses to ACh and increased the sensitivity to NO in SHR-SP. PMID:10602331

  1. Administration of human recombinant activated protein C is not associated with pancreatic parenchymal haemorrhage in L-arginine-induced experimental acute pancreatitis.

    PubMed

    Jamdar, Saurabh; Babu, Benoy I; Nirmalan, Mahesh; Jeziorska, Maria; McMahon, Raymond F T; Siriwardena, Ajith K

    2013-11-10

    Microvascular thrombosis is a critical event in severe acute pancreatitis. Human recombinant activated protein C (Xigris®, Eli Lilly, Indianapolis, IN, USA) modulates the interplay between pro-inflammatory and pro-coagulant pathways and maintains microvascular patency. However, the anticoagulant properties of Xigris® may precipitate bleeding from the inflamed pancreas. This study tests the hypothesis that Xigris® can ameliorate experimental acute pancreatitis without causing pancreatic haemorrhage. Sprague Dawley rats were allocated as follows: Group 1: control (n=7); Group 2: acute pancreatitis (n=6); Group 3: administration of Xigris® 500 µg/kg body weight before induction of acute pancreatitis (n=6); and Group 4: Administration of Xigris® 500 µg/kg body weight 30 minutes after induction of acute pancreatitis (n=6). Acute pancreatitis was induced by intraperitoneal administration of L-arginine 300 mg/100 g body weight. Animals were sacrificed at 48 hours and biochemical, haematological, and histological markers of pancreatic haemorrhage and inflammation assessed. Median lipase in animals with acute pancreatitis was 10 U/mL (range: 7-16 U/mL) compared to 5.5 (range: 3-8 U/mL) in controls (P=0.028). Lipase was also elevated in animals given Xigris® both before (12 U/mL, range: 8-22 U/mL; P=0.031 vs. control group) and after (46 U/mL, range: 9-71 U/mL; P=0.015 vs. control group) induction of acute pancreatitis). Haemoglobin levels were similar among all groups (P=0.323). There was no histological evidence of pancreatic haemorrhage in animals treated with Xigris®. Pre-treatment with Xigris® was associated with a significant reduction in pancreatic injury. This effect was absent when Xigris® was administered after induction of acute pancreatitis. Xigris® did not lead to pancreatic haemorrhage in experimental acute pancreatitis. Administration of Xigris® prior to induction of acute pancreatitis was associated with amelioration of injury. This effect was

  2. The effect of nitric oxide synthase inhibitors nitro-L-arginine and 7-nitroindazole on spatial learning and motor functions in Lurcher mutant and wild type mice.

    PubMed

    Markvartová, V; Vozeh, F

    2008-01-01

    Nitric oxide (NO) is an intercellular messenger that, among other things, plays an important role in the nervous system as a gaseous neurotransmitter, modulating long-term potentiation (LTP) induction of synaptic transmission. LTP has been suggested to be the basis of memory formation. On the other hand NO also participates in excitotoxic processes which play an important role in many neuropathological states. The aim of this work was to observe the effect of two NO synthase (NOS) inhibitors (N omega-Nitro-L-arginine, NA; 7-nitroindazole, NI) on spontaneous behaviour, spatial learning and motor functions in Lurcher (+/Lc) and wild type (+/+) mice, derived from the B6CBA strain. Heterozygous Lurcher mutant mice represent a natural model of the olivocerebellar degeneration. They suffer from postnatal, practically total, extinction of cerebellar Purkinje cells (due to the excitotoxic apoptosis) and a partial decrease of granule cells and inferior olive neurons (ION) because of the lost target of their axons. +/+ animals are healthy littermates of +/Lc. NA is a nonselective NOS inhibitor which influences, except neuronal (n), also endothelial (e) NOS with an impact on blood pressure, NI is a selective nNOS inhibitor without any circulatory effect. The adult animals of both types (+/Lc; +/+) were influenced by acute administration of both inhibitors (25 mg/kg i.p. 30 min. before experiments) and newborns only by both acute and long-term administration of NI (1 month, starting from postnatal day 2, P2). Control solutions - saline or solvents of both NA and NI inhibitors--diluted 1M HCl and dimethyl sulfoxide (DMSO) respectively, were given at a relevant volume in the same way. The effect of both inhibitors and control solutions on motor functions was tested using four standard procedures (horizontal wire, slanting ladder, rotating cylinder, foot-bridge); in newborns at the age of 14 days. Spatial learning ability was examined in five-day long procedure in the Morris

  3. Elevated levels of branched-chain amino acids have little effect on pancreatic islet cells, but L-arginine impairs function through activation of the endoplasmic reticulum stress response.

    PubMed

    Mullooly, Niamh; Vernon, Wendy; Smith, David M; Newsholme, Philip

    2014-03-01

    Recent metabolic profiling studies have identified a correlation between branched-chain amino acid levels, insulin resistance associated with prediabetes and susceptibility to type 2 diabetes. Glucose and lipids in chronic excess have been reported to induce toxic effects in pancreatic β-cells, but the effect of elevated amino acid concentrations on primary islet cell function has not been investigated to date. The aim of this study was to investigate the effect of chronic exposure to various amino acids on islet cell function in vitro. Isolated rat islets were incubated over periods of 48 h with a range of concentrations of individual amino acids (0.1 μm to 10 mm). After 48 h, islets were assessed for glucose-dependent insulin secretion capacity, proliferation or islet cell apoptosis. We report that elevated levels of branched-chain amino acids have little effect on pancreatic islet cell function or viability; however, increased levels of the amino acid l-arginine were found to be β-cell toxic, causing a dose-dependent decrease in insulin secretion accompanied by a decrease in islet cell proliferation and an increase in islet cell apoptosis. These effects were not due to l-arginine-dependent increases in production of nitric oxide but arose through elicitation of the islet cell endoplasmic reticulum stress response. This novel finding indicates, for the first time, that the l-arginine concentration in vitro may impact negatively on islet cell function, thus indicating further complexity in relationship to in vivo susceptibility of β-cells to nutrient-induced dysfunction.

  4. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats.

    PubMed

    Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

    2016-01-01

    Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and

  5. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats

    PubMed Central

    Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

    2016-01-01

    Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and

  6. [N(omega)-nitro-L-arginine methyl ester inhibits the up-regulated expression of neuronal nitric oxide synthase/NMDA receptor in the morphine analgesia tolerance rats].

    PubMed

    Yu, Ling; Xue, Fu-Shan; Li, Cheng-Wen; Xu, Ya-Chao; Zhang, Guo-Hua; Liu, Kun-Peng; Liu, Yi; Sun, Hai-Tao

    2006-12-25

    The effect of systemic administration of nonspecific nitric oxide synthase inhibitor (N(omega)-nitro-L-arginine methyl ester, L-NAME) on morphine analgesia tolerance was observed by using the thermal tail-flick method, and the roles of NO and NMDA receptors in morphine analgesia tolerance were evaluated on the basis of the expressions of nNOS mRNA, NR1A mRNA and NR2A mRNA in spinal cord and midbrain. Thirty-six healthy adult Sprague-Dawley rats were randomly divided into six groups (6 rats per group). Group 1, control group, received a subcutaneous (s.c.) injection of normal saline (1 ml); Groups 2, 3, 4, 5 and 6, the treatment groups received s.c. injection of L-NAME 10 mg/kg, L-NAME 20 mg/kg, morphine 10 mg/kg, L-NAME 10 mg/kg + morphine 10 mg/kg, and L-NAME 20 mg/kg + morphine 10 mg/kg, respectively. All rats received s.c. injections twice per day (8:00 and 17:00). The tail-flick latency (TFL) was measured in each rat before the injection as a baseline value, and then TFL at 50 min after the 1st injection every day as the measuring values. The animals (except for groups 2 and 5) were decapitated at 80 min after the last injection on the 8th day. The spinal segments and midbrain were removed for analysis of nNOS mRNA, NR1A mRNA and NR2A mRNA expressions by the RT-PCR method. The results showed that TFL remained unchangeable in group 2 compared with baseline value during the 7-day observation, while increased significantly on the 7th day in group 3. In group 4, TFL was longest on the 1st day, then decreased gradually from the 2nd day to the 6th day, and restored to the baseline value on the 6th day. In group 5, TFL showed a decreasing tendency during the 7-day observation, but was still significantly longer than the baseline value on the 7th day. The changes of TFL obtained in group 6 were similar to those in group 5. The results of RT-PCR showed that as compared with group 1, nNOS mRNA expressions in spinal cord and midbrain were significantly down-regulated in

  7. The effects of bupivacaine, L-nitro-L-arginine-methyl ester, and phenylephrine on cardiovascular adaptations to asphyxia in the preterm fetal lamb.

    PubMed

    Santos, A C; Yun, E M; Bobby, P D; Noble, G; Arthur, G R; Finster, M

    1997-12-01

    The preterm fetal lamb that is exposed to clinically relevant plasma concentrations of lidocaine loses its cardiovascular adaptations to asphyxia, and its condition deteriorates further. Nitric oxide (NO) is an important regulator of vascular tone, and local anesthetics are known to inhibit endothelium-dependent vasodilation. The purpose of the present study was to determine whether the adverse effects of lidocaine noted in the preterm fetal lamb also occur with bupivacaine and whether the inhibition of NO results in effects similar to those of bupivacaine. Thirty-two chronically prepared pregnant sheep were studied at 117-119 days' gestation. Maternal and fetal blood pressure, heart rate, and acid-base state were evaluated. Fetal organ blood flows were determined using 15-microM diameter dye-labeled microspheres. After a control period, mild to moderate asphyxia (fetal PaO2 15 mm Hg) was induced by partial umbilical cord occlusion and maintained throughout the experiment. Ewes in Group I (n = 13) were given a two-step intravenous infusion of bupivacaine for 180 min. Fetuses in Group II (n = 12) received an intravenous injection of L-nitro-L-arginine-methyl ester (L-NAME) (25 mg/kg), and measurements were taken 10 and 30 min after the injection. A third group (Group III) of fetuses (n = 7) were given an intravenous infusion of phenylephrine to mimic the blood pressure increases noted in L-NAME-treated fetuses. At 90 min of stable asphyxia, there was a significant decrease in fetal PaO2 and pHa and an increase in PaCO2 and mean arterial blood pressure. There was also an increase in blood flow to the adrenals, myocardium, and cerebral cortex, whereas blood flow to the placenta decreased. Administration of bupivacaine during asphyxia did not affect the changes in mean arterial blood pressure and acid-base state but did abolish the increases in blood flows to the myocardium and cerebral cortex. Injection of L-NAME to the asphyxiated fetus resulted in an increase in

  8. Differential Effects of Leucine Supplementation in Young and Aged Mice at the Onset of Skeletal Muscle Regeneration

    PubMed Central

    Perry, Richard A.; Brown, Lemuel A.; Lee, David E.; Brown, Jacob L.; Baum, Jamie I.; Greene, Nicholas P.; Washington, Tyrone A.

    2016-01-01

    Aging decreases the ability of skeletal muscle to respond to injury. Leucine has been demonstrated to target protein synthetic pathways in skeletal muscle thereby enhancing this response. However, the effect of aging on leucine-induced alterations in protein synthesis at the onset of skeletal muscle regeneration has not been fully elucidated. The purpose of this study was to determine if aging alters skeletal muscle regeneration and leucine-induced alterations in markers of protein synthesis. The tibialis anterior of young (3 months) and aged (24 months) female C57BL/6J mice were injected with either bupivacaine or PBS, and the mice were given ad libitum access to leucine-supplemented or normal drinking water. Protein and gene expression of markers of protein synthesis and degradation, respectively, were analyzed at three days post-injection. Following injury in young mice, leucine supplementation was observed to elevate only p-p70S6K. In aged mice, leucine was shown to elicit higher p-mTOR content with and without injury, and p-4EBP-1 content post-injury. Additionally in aged mice, leucine was shown to elicit higher content of relative p70S6K post-injury. Our study shows that leucine supplementation affects markers of protein synthesis at the onset of skeletal muscle regeneration differentially in young and aged mice. PMID:27327351

  9. Omega-3 Fatty Acids Supplementation Differentially Modulates the SDF-1/CXCR-4 Cell Homing Axis in Hypertensive and Normotensive Rats.

    PubMed

    Halmenschlager, Luiza; Lehnen, Alexandre Machado; Marcadenti, Aline; Markoski, Melissa Medeiros

    2017-08-01

    We assessed the effect of acute and chronic dietary supplementation of ω-3 on lipid metabolism and cardiac regeneration, through its influence on the Stromal Derived Factor-1 (SDF-1) and its receptor (CXCR4) axis in normotensive and hypertensive rats. Male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were allocated in eight groups (of eight animals each), which received daily orogastric administration of ω-3 (1 g) for 24 h, 72 h or 2 weeks. Blood samples were collected for the analysis of the lipid profile and SDF-1 systemic levels (ELISA). At the end of the treatment period, cardiac tissue was collected for CXCR4 expression analysis (Western blot). The use of ω-3 caused a reduction in total cholesterol levels ( p = 0.044), and acutely activated the SDF-1/CXCR4 axis in normotensive animals ( p = 0.037). In the presence of the ω-3, after 72 h, SDF-1 levels decreased in WKY and increased in SHR ( p = 0.017), and tissue expression of the receptor CXCR4 was higher in WKY than in SHR ( p = 0.001). The ω-3 fatty acid supplementation differentially modulates cell homing mediators in normotensive and hypertensive animals. While WKY rats respond acutely to omega-3 supplementation, showing increased release of SDF-1 and CXCR4, SHR exhibit a weaker, delayed response.

  10. Increasing the availability of l-arginine and nitric oxide increases sensitivity of nitrous oxide (N2O)-insensitive inbred mice to N2O-induced antinociception.

    PubMed

    Chung, Eunhee; Ohgami, Yusuke; Quock, Raymond M

    2016-07-01

    Nitrous oxide (N2O)-induced antinociception in mice is dependent on the neuromodulator nitric oxide (NO). In contrast to C57BL/6J (B6) mice, DBA/2J (D2) mice fail to respond to N2O with a robust antinociceptive response or with an increase in brain nitric oxide synthase (NOS) enzyme activity, suggesting that failure of D2 mice to respond to N2O might result from a deficit of NO function. Therefore, it was of interest to determine whether increasing the availability of NO might increase sensitivity of D2 mice to N2O. Male D2 mice were pretreated with sub-antinociceptive intracerebroventricular doses of the NO donor 3-morpholinosydnoimine or the NO precursor l-arginine then assessed for responsiveness to N2O-induced antinociception using the acetic acid abdominal constriction test. Both pretreatments increased the antinociceptive responsiveness of D2 mice to N2O. These results indicate that the NOS enzyme in D2 mice is functional and that the deficit in NO function that obstructs sensitivity to N2O-induced antinociception may lie in availability or utilization of l-arginine. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Influence of nanosecond pulsed plasma on the non-enzymatic pathway for the generation of nitric oxide from L-arginine and the modification of graphite oxide to increase the solar cell efficiency.

    PubMed

    Attri, Pankaj; Park, Ji Hoon; Gaur, Jitender; Kumar, Naresh; Park, Dae Hoon; Jeon, Su Nam; Park, Bong Sang; Chand, Suresh; Uhm, Han Sup; Choi, Eun Ha

    2014-09-14

    In this work, we demonstrated the action of nanosecond pulsed plasma (NPP) on the generation of nitric oxide (NO) from the non-enzymatic pathway and on the modification of graphite oxide (GO) sheets to increase polymer solar cells (PSCs) efficiency. NO is an important signal and an effector molecule in animals, which is generated from the enzyme-catalyzed oxidation of L-arginine to NO and L-citrulline. Hence, L-arginine is an important biological precursor for NO formation. Therefore, we developed a new non-enzymatic pathway for the formation of NO and L-citrulline using NPP and characterized the pathway using NO detection kit, NMR, liquid chromatography/capillary electrophoresis-mass spectrometry (LC/CE-MS) for both quantitative and qualitative bioanalysis. We then synthesized and modified the functional groups of GO using NPP, and it was characterised by X-ray photoelectron spectroscopy (XPS), confocal Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM) imaging, cathodoluminescence (CL) and work function using γ-FIB. Further, we also tested the power conversion efficiency of the PSCs devices with modified GO that is similar to the one obtained with poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) as HTL. This work is perceived to have great implications for inexpensive and efficient methodology for NO generation and modification of GO, which are applicable in materials from nanomaterials to biomolecules.

  12. Artemisia supplementation differentially affects the mucosal and luminal ileal microbiota of diet-induced obese mice

    PubMed Central

    Shawna, Wicks; M., Taylor Christopher; Meng, Luo; Eugene, Blanchard IV; David, Ribnicky; T., Cefalu William; L., Mynatt Randall; A., Welsh David

    2014-01-01

    Objective The gut microbiome has been implicated in obesity and metabolic syndrome; however, most studies have focused on fecal or colonic samples. Several species of Artemisia have been reported to ameliorate insulin signaling both in vitro and in vivo. The aim of this study was to characterize the mucosal and luminal bacterial populations in the terminal ileum with or without supplementation with Artemisia extracts. Materials/Methods Following 4 weeks of supplementation with different Artemisia extracts (PMI 5011, Santa or Scopa), diet-induced obese mice were sacrificed and luminal and mucosal samples of terminal ileum were used to evaluate microbial community composition by pyrosequencing of 16S rDNA hypervariable regions. Results Significant differences in community structure and membership were observed between luminal and mucosal samples, irrespective of diet group. All Artemisia extracts increased the Bacteroidetes:Firmicutes ratio in mucosal samples. This effect was not observed in the luminal compartment. There was high inter-individual variability in the phylogenetic assessments of the ileal microbiota, limiting the statistical power of this pilot investigation. Conclusions Marked differences in bacterial communities exist dependent upon the biogeographic compartment in the terminal ileum. Future studies testing the effects of Artemisia or other botanical supplements require larger sample sizes for adequate statistical power. PMID:24985102

  13. Vitamin C and E chronic supplementation differentially affect hepatic insulin signaling in rats.

    PubMed

    Ali, Mennatallah A; Eid, Rania M H M; Hanafi, Mervat Y

    2018-02-01

    Vitamin C and vitamin E supplementations and their beneficial effects on type 2 diabetes mellitus (T2DM) have been subjected to countless controversial data. Hence, our aim is to investigate the hepatic molecular mechanisms of any diabetic predisposing risk of the chronic administration of different doses of vitamin E or vitamin C in rats. The rats were supplemented with different doses of vitamin C or vitamin E for eight months. Vitamin C and vitamin E increased fasting blood glucose, insulin, and homeostasis model assessment index for insulin resistance (HOMA). Vitamin C disrupted glucose tolerance by attenuating upstream hepatic insulin action through impairing the phosphorylation and activation of insulin receptor and its subsequent substrates; however, vitamin E showed its effect downstream insulin receptor in the insulin signaling pathway, reducing hepatic glucose transporter-2 (GLUT2) and phosphorylated protein kinase (p-Akt). Moreover, both vitamins showed their antioxidant capabilities [nuclear factor-erythroid-2-related factor 2 (Nrf2), total and reduced glutathione] and their negative effect on Wnt pathway [phosphorylated glycogen synthase kinase-3β (p-GSK-3β)], by altering the previously mentioned parameters, inevitably leading to severe reduction of reactive oxygen species (ROS) below the physiological levels. In conclusion, a detrimental effect of chronic antioxidant vitamins supplementation was detected; leading to insulin resistance and impaired glucose tolerance obviously through different mechanisms. Overall, these findings indicate that the conventional view that vitamins promote health benefits and delay chronic illnesses and aging should be modified or applied with caution. Copyright © 2017. Published by Elsevier Inc.

  14. Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation

    PubMed Central

    2013-01-01

    Background Betaine (BET) is a component of many foods, including spinach and wheat. It is an essential osmolyte and a source of methyl groups. Recent studies have hypothesized that BET might play a role in athletic performance. However, BET effects on skeletal muscle differentiation and hypertrophy are still poorly understood. Methods We examined BET action on neo myotubes maturation and on differentiation process, using C2C12 murine myoblastic cells. We used RT2-PCR array, Western blot and immunofluorescence analysis to study the BET effects on morphological features of C2C12 and on signaling pathways involved in muscle differentiation and hypertrophy. Results We performed a dose–response study, establishing that 10 mM BET was the dose able to stimulate morphological changes and hypertrophic process in neo myotubes. RT2-PCR array methodology was used to identify the expression profile of genes encoding proteins involved in IGF-1 pathway. A dose of 10 mM BET was found to promote IGF-1 receptor (IGF-1 R) expression. Western blot and immunofluorescence analysis, performed in neo myotubes, pointed out that 10 mM BET improved IGF-1 signaling, synthesis of Myosin Heavy Chain (MyHC) and neo myotubes length. In addition, we investigated BET role on myoblasts proliferation and differentiation. During proliferation, BET did not modify C2C12 proliferative rate, but promoted myogenic induction, enhancing MyoD protein content and cellular elongation. During differentiation, BET caused an increase of muscle-specific markers and IGF-1 R protein levels. Conclusions Our findings provide the first evidence that BET could promote muscle fibers differentiation and increase myotubes size by IGF-1 pathway activation, suggesting that BET might represent a possible new drug/integrator strategy, not only in sport performance but also in clinical conditions characterized by muscle function impairment. PMID:23870626

  15. In vitro activity of gentamicin, vancomycin or amikacin combined with EDTA or l-arginine as lock therapy against a wide spectrum of biofilm-forming clinical strains isolated from catheter-related infections.

    PubMed

    Lebeaux, David; Leflon-Guibout, Véronique; Ghigo, Jean-Marc; Beloin, Christophe

    2015-01-01

    Treatment of catheter-related bloodstream infections (CRBSI) is hampered by the characteristic tolerance of bacterial biofilms towards antibiotics. Our objective was to study the effect of the combination of antibiotics and the alkaline amino acid l-arginine or the cation chelator EDTA on the bacterial killing of in vitro biofilms formed by an array of clinical strains responsible for CRBSI and representative of epidemiologically relevant bacterial species. Among 32 strains described in a previous clinical study, we focused on the most antibiotic-tolerant strains including CoNS (n = 4), Staphylococcus aureus (n = 4), Enterococcus faecalis (n = 2), Pseudomonas aeruginosa (n = 4) and Enterobacteriaceae (n = 4). We used an in vitro biofilm model (96-well plate assay) to study biofilm tolerance and tested various combinations of antibiotics and non-antibiotic adjuvants. Gentamicin, amikacin or vancomycin was combined with disodium EDTA or l-arginine for 24 h to reproduce the antibiotic lock therapy (ALT) approach. Killing of biofilm bacteria was measured by cfu quantification after a vigorous step of pipetting up and down in order to detach all biofilm bacteria from the surface of the wells. Both of our adjuvant strategies significantly increased the effect of antibiotics against biofilms formed by Gram-positive and Gram-negative bacterial pathogens. The combination of gentamicin + EDTA was active against all tested strains apart from one P. aeruginosa. The combination of gentamicin + l-arginine was active against most of the tested strains with the notable exception of CoNS for which no potentiation was observed. We also demonstrated that amikacin + EDTA was active against Gram-negative bacteria and that vancomycin + EDTA was active against Gram-positive bacteria. The addition of EDTA enhanced the activity of gentamicin, amikacin and vancomycin against biofilms formed by a wide spectrum of bacterial strains responsible for CRBSI.

  16. Betaine supplement enhances skeletal muscle differentiation in murine myoblasts via IGF-1 signaling activation.

    PubMed

    Senesi, Pamela; Luzi, Livio; Montesano, Anna; Mazzocchi, Nausicaa; Terruzzi, Ileana

    2013-07-19

    Betaine (BET) is a component of many foods, including spinach and wheat. It is an essential osmolyte and a source of methyl groups. Recent studies have hypothesized that BET might play a role in athletic performance. However, BET effects on skeletal muscle differentiation and hypertrophy are still poorly understood. We examined BET action on neo myotubes maturation and on differentiation process, using C2C12 murine myoblastic cells. We used RT2-PCR array, Western blot and immunofluorescence analysis to study the BET effects on morphological features of C2C12 and on signaling pathways involved in muscle differentiation and hypertrophy. We performed a dose-response study, establishing that 10 mM BET was the dose able to stimulate morphological changes and hypertrophic process in neo myotubes. RT2-PCR array methodology was used to identify the expression profile of genes encoding proteins involved in IGF-1 pathway. A dose of 10 mM BET was found to promote IGF-1 receptor (IGF-1 R) expression. Western blot and immunofluorescence analysis, performed in neo myotubes, pointed out that 10 mM BET improved IGF-1 signaling, synthesis of Myosin Heavy Chain (MyHC) and neo myotubes length. Our findings provide the first evidence that BET could promote muscle fibers differentiation and increase myotubes size by IGF-1 pathway activation, suggesting that BET might represent a possible new drug/integrator strategy, not only in sport performance but also in clinical conditions characterized by muscle function impairment.

  17. Effect of selenium supplementation for protection of salivary glands from iodine-131 radiation damage in patients with differentiated thyroid cancer.

    PubMed

    Son, Haiyoung; Lee, Sang Mi; Yoon, Ra Gyoung; Lee, Hakmin; Lee, Ilkyun; Kim, Soon; Chung, Woong Youn; Lee, Jeong Won

    2017-01-01

    In the current study, we examined whether selenium supplementation during iodine-131 ( 131 I) treatment had a radio-protective effect on salivary glands. Sixteen patients with differentiated thyroid cancer were prospectively enrolled in the study. Patients after total thyroidectomy, before 131 I treatment, were divided into two groups; 8 patients in the selenium group and 8 patients in the control group. Patients in the selenium group received 300νg of selenium orally for 10 days, from 3 days before to 6 days after 131 I treatment. The control group received a placebo over the same period. To assess salivary gland function, salivary gland scintigraphy was performed before and 6 months after 131 I treatment. Serum amylase and whole blood selenium levels were measured before and 2 days and 6 months after 131 I treatment. Using salivary gland scintigraphy, maximum uptake ratio (MUR), maximum secretion percentage (MSP), and ejection fraction (EF) of each salivary gland were calculated. Baseline clinical characteristics, baseline amylase and selenium levels, and parameters of baseline salivary gland scintigraphy were not significantly different between selenium and control groups (P>0.05). On a blood test performed 2 days after 131 I treatment, the selenium group showed a significantly higher whole blood selenium level (P=0.008) and significantly lower serum amylase level (P=0.009) than the control group. On follow-up salivary gland scintigraphy, the control group showed significantly decreased, MUR of the bilateral parotid and left submandibular glands, MSP of the bilateral parotid and submandibular glands, and EF of the left submandibular glands (P<0.05), while the selenium group only had a significant decrease in MSP of the right submandibular gland and EF of the left submandibular gland (P<0.05). Selenium supplementation during 131 I treatment was effective to reduce salivary glands damage by 131 I radiation in patients with differentiated thyroid cancer.

  18. Modification of the electrical, optical and thermal properties of L-Arginine Perchlorate single crystals by 5 kGy and 8 kGy electron beam irradiation for optoelectronic devices

    NASA Astrophysics Data System (ADS)

    Thomas, Prince; Santhosh Kumar, R.; Sreekanth, G.; John, Bitto; Sanjeev, Ganesh; Joseph, Ginson P.

    2017-11-01

    This paper attempts to elucidate the effect of 5 kGy and 8 kGy electron irradiation on the optical, thermal and electrical properties of a prominent amino acid crystal, L-Arginine Perchlorate (LAPCl) grown by low-temperature solution growth technique. Optical absorption studies revealed that the UV lower cut-off wavelength shift towards the higher wavelength region (Red shift), the optical band gap of LAPCl were found to be decreasing while the Urbach energy was found to be increasing with increasing the dosage of irradiation. Fourier Transform Infrared (FT-IR) spectroscopic result showed that peak intensities corresponding to typical bonding increase with the increase in electron beam irradiation dosage. Electrical studies revealed that the dielectric constant, loss and conductivity of the sample increases with increasing the dosage of irradiation. The behaviour of electrical properties on temperature and thermal properties has also been investigated.

  19. Safety and performance benefits of arginine supplements for military personnel: a systematic review.

    PubMed

    Brooks, James R; Oketch-Rabah, Hellen; Low Dog, Tieraona; Gorecki, Dennis K J; Barrett, Marilyn L; Cantilena, Louis; Chung, Mei; Costello, Rebecca B; Dwyer, Johanna; Hardy, Mary L; Jordan, Scott A; Maughan, Ronald J; Marles, Robin J; Osterberg, Robert E; Rodda, Bruce E; Wolfe, Robert R; Zuniga, Jorge M; Valerio, Luis G; Jones, Donnamaria; Deuster, Patricia; Giancaspro, Gabriel I; Sarma, Nandakumara D

    2016-11-01

    Dietary supplements are widely used by military personnel and civilians for promotion of health. The objective of this evidence-based review was to examine whether supplementation with l-arginine, in combination with caffeine and/or creatine, is safe and whether it enhances athletic performance or improves recovery from exhaustion for military personnel. Information from clinical trials and adverse event reports were collected from 17 databases and 5 adverse event report portals. Studies and reports were included if they evaluated the safety and the putative outcomes of enhanced performance or improved recovery from exhaustion associated with the intake of arginine alone or in combination with caffeine and/or creatine in healthy adults aged 19 to 50 years. Information related to population, intervention, comparator, and outcomes was abstracted. Of the 2687 articles screened, 62 articles meeting the inclusion criteria were analyzed. Strength of evidence was assessed in terms of risk of bias, consistency, directness, and precision. Most studies had few participants and suggested risk of bias that could negatively affect the results. l-Arginine supplementation provided little enhancement of athletic performance or improvements in recovery. Short-term supplementation with arginine may result in adverse gastrointestinal and cardiovascular effects. No information about the effects of arginine on the performance of military personnel was available. The available information does not support the use of l-arginine, either alone or in combination with caffeine, creatine, or both, to enhance athletic performance or improve recovery from exhaustion. Given the information gaps, an evidence-based review to assess the safety or effectiveness of multi-ingredient dietary supplements was not feasible, and therefore the development of a computational model-based approach to predict the safety of multi-ingredient dietary supplements is recommended. © The Author(s) 2016. Published by

  20. Fish oil and krill oil supplementations differentially regulate lipid catabolic and synthetic pathways in mice

    PubMed Central

    2014-01-01

    Background Marine derived oils are rich in long-chain polyunsaturated omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have long been associated with health promoting effects such as reduced plasma lipid levels and anti-inflammatory effects. Krill oil (KO) is a novel marine oil on the market and is also rich in EPA and DHA, but the fatty acids are incorporated mainly into phospholipids (PLs) rather than triacylglycerols (TAG). This study compares the effects of fish oil (FO) and KO on gene regulation that influences plasma and liver lipids in a high fat diet mouse model. Methods Male C57BL/6J mice were fed either a high-fat diet (HF) containing 24% (wt/wt) fat (21.3% lard and 2.3% soy oil), or the HF diet supplemented with FO (15.7% lard, 2.3% soy oil and 5.8% FO) or KO (15.6% lard, 2.3% soy oil and 5.7% KO) for 6 weeks. Total levels of cholesterol, TAG, PLs, and fatty acid composition were measured in plasma and liver. Gene regulation was investigated using quantitative PCR in liver and intestinal epithelium. Results Plasma cholesterol (esterified and unesterified), TAG and PLs were significantly decreased with FO. Analysis of the plasma lipoprotein particles indicated that the lipid lowering effect by FO is at least in part due to decreased very low density lipoprotein (VLDL) content in plasma with subsequent liver lipid accumulation. KO lowered plasma non-esterified fatty acids (NEFA) with a minor effect on fatty acid accumulation in the liver. In spite of a lower omega-3 fatty acid content in the KO supplemented diet, plasma and liver PLs omega-3 levels were similar in the two groups, indicating a higher bioavailability of omega-3 fatty acids from KO. KO more efficiently decreased arachidonic acid and its elongation/desaturation products in plasma and liver. FO mainly increased the expression of several genes involved in fatty acid metabolism, while KO specifically decreased the expression of genes involved in

  1. Nitrate supplementation and human exercise performance: too much of a good thing?

    PubMed

    Poortmans, Jacques R; Gualano, Bruno; Carpentier, Alain

    2015-11-01

    Ergogenic supplements in sport events are widely used by popular and competitive athletes to enhance performance and reduce oxygen cost. Beetroot juice and nitrate salts have been increasingly used for the past 5-6 years. The present review discusses the scientific background, the efficiency and potential adverse effects of excessive nitrate supplementation. There is clear evidence that nitrate from different food ingredients (such as beetroot juice and other vegetables) is converted into nitrite and possibly into nitric oxide, which may promote vasodilation, angiogenesis and mitochondrial biogenesis. The high affinity of nitric oxide towards different enzyme pathways inhibits excessive mitochondrial respiration and, therefore, tissue oxygen consumption. In addition, L-arginine supplements are proposed to stimulate nitric oxide synthesis in the endothelium. On the basis of these biochemical properties, nitrate supplementation has been suggested to athletes to enhance exercise performance. The recent publications in human individuals based on L-arginine, beetroot juice or nitrate supplementation revealed either a minor positive effect or no systematic effect on exercise performance, especially in trained athletes. Of note, the sugar content of whole beetroot juice might induce a slightly more pronounced effect. Although reasonable intake of nitrate salts (up to 1 g/day) has no detrimental effect on kidney function, the risk and benefit of higher nitrate intake needs to be evaluated to define the optimal range of supplementation.

  2. Inner-sphere oxidation of ternary iminodiacetatochromium(III) complexes involving DL-valine and L-arginine as secondary ligands. Isokinetic relationship for the oxidation of ternary iminodiacetato-chromium(III) complexes by periodate.

    PubMed

    Ewais, Hassan A; Dahman, Faris D; Abdel-Khalek, Ahmed A

    2009-02-04

    In this paper, the kinetics of oxidation of [CrIII(HIDA)(Val)(H2O)2]+ and [CrIII(HIDA)(Arg)(H2O)2]+ (HIDA = iminodiacetic acid, Val = DL-valine and Arg = L-arginine) were studied. The choice of ternary complexes was attributed to two considerations. Firstly, in order to study the effect of the secondary ligands DL-valine and L-arginine on the stability of binary complex [CrIII(HIDA)(IDA)(H2O)] towards oxidation. Secondly, transition metal ternary complexes have received particular focus and have been employed in mapping protein surfaces as probes for biological redox centers and in protein capture for both purification and study. The results have shown that the reaction is first order with respect to both [IO4(-)] and the complex concentration, and the rate increases over the pH range 2.62 - 3.68 in both cases. The experimental rate law is consistent with a mechanism in which both the deprotonated forms of the complexes [CrIII(IDA)(Val)(H2O)2] and [CrIII(IDA)(Arg)(H2O)2] are significantly more reactive than the conjugate acids. The value of the intramolecular electron transfer rate constant for the oxidation of [CrIII(HIDA)(Arg)(H2O)2]+, k3 (1.82 x 10(-3) s(-1)), is greater than the value of k1 (1.22 x 10(-3) s(-1)) for the oxidation of [CrIII(HIDA)(Val)(H2O)2]+ at 45.0 degrees C and I = 0.20 mol dm(-3). It is proposed that electron transfer proceeds through an inner-sphere mechanism via coordination of IO4(-) to chromium(III). The oxidation of [CrIII(HIDA)(Val)(H2O)2]+ and [CrIII(HIDA)(Arg)(H2O)2]+ by periodate may proceed through an inner-sphere mechanism via two electron transfer giving chromium(VI). The value of the intramolecular electron transfer rate constant for the oxidation of [CrIII(HIDA)(Arg)(H2O)2]+, k3, is greater than the value of k1 for the oxidation of [CrIII(HIDA)(Val)(H2O)2]+. A common mechanism for the oxidation of ternary iminodiacetatochromium(III) complexes by periodate is proposed, and this is supported by an excellent isokinetic

  3. Inner-sphere oxidation of ternary iminodiacetatochromium(III) complexes involving DL-valine and L-arginine as secondary ligands. Isokinetic relationship for the oxidation of ternary iminodiacetato-chromium(III) complexes by periodate

    PubMed Central

    Ewais, Hassan A; Dahman, Faris D; Abdel-Khalek, Ahmed A

    2009-01-01

    Background In this paper, the kinetics of oxidation of [CrIII(HIDA)(Val)(H2O)2]+ and [CrIII(HIDA)(Arg)(H2O)2]+ (HIDA = iminodiacetic acid, Val = DL-valine and Arg = L-arginine) were studied. The choice of ternary complexes was attributed to two considerations. Firstly, in order to study the effect of the secondary ligands DL-valine and L-arginine on the stability of binary complex [CrIII(HIDA)(IDA)(H2O)] towards oxidation. Secondly, transition metal ternary complexes have received particular focus and have been employed in mapping protein surfaces as probes for biological redox centers and in protein capture for both purification and study. Results The results have shown that the reaction is first order with respect to both [IO4-] and the complex concentration, and the rate increases over the pH range 2.62 – 3.68 in both cases. The experimental rate law is consistent with a mechanism in which both the deprotonated forms of the complexes [CrIII(IDA)(Val)(H2O)2] and [CrIII(IDA)(Arg)(H2O)2] are significantly more reactive than the conjugate acids. The value of the intramolecular electron transfer rate constant for the oxidation of [CrIII(HIDA)(Arg)(H2O)2]+, k3 (1.82 × 10-3 s-1), is greater than the value of k1 (1.22 × 10-3 s-1) for the oxidation of [CrIII(HIDA)(Val)(H2O)2]+ at 45.0°C and I = 0.20 mol dm-3. It is proposed that electron transfer proceeds through an inner-sphere mechanism via coordination of IO4- to chromium(III). Conclusion The oxidation of [CrIII(HIDA)(Val)(H2O)2]+ and [CrIII(HIDA)(Arg)(H2O)2]+ by periodate may proceed through an inner-sphere mechanism via two electron transfer giving chromium(VI). The value of the intramolecular electron transfer rate constant for the oxidation of [CrIII(HIDA)(Arg)(H2O)2]+, k3, is greater than the value of k1 for the oxidation of [CrIII(HIDA)(Val)(H2O)2]+. A common mechanism for the oxidation of ternary iminodiacetatochromium(III) complexes by periodate is proposed, and this is supported by an excellent

  4. Bone marrow stromal cells on a three-dimensional bioactive fiber mesh undergo osteogenic differentiation in the absence of osteogenic media supplements: the effect of silanol groups.

    PubMed

    Rodrigues, Márcia T; Leonor, Isabel B; Gröen, Nathalie; Viegas, Carlos A; Dias, Isabel R; Caridade, Sofia G; Mano, João F; Gomes, Manuela E; Reis, Rui L

    2014-10-01

    Osteogenic differentiation is a tightly regulated process dependent on the stimuli provided by the micro-environment. Silicon-substituted materials are known to have an influence on the osteogenic phenotype of undifferentiated and bone-derived cells. This study aims to investigate the bioactivity profile as well as the mechanical properties of a blend of starch and poly-caprolactone (SPCL) polymeric fiber mesh scaffolds functionalized with silanol (Si-OH) groups as key features for bone tissue engineering strategies. The scaffolds were made from SPCL by a wet spinning technique. A calcium silicate solution was used as a non-solvent to develop an in situ functionalization with Si-OH groups in a single-step approach. We also explored the relevance of silicon incorporated in SPCL-Si scaffolds to the in vitro osteogenic process of goat bone marrow stromal cells (gBMSCs) with and without osteogenic supplements in the culture medium. We hypothesized that SPCL-Si scaffolds could act as physical and chemical millieus to induce per se the osteogenic differentiation of gBMSCs. Results show that osteogenic differentiation of gBMSCs and the production of a mineralized extracellular matrix on bioactive SPCL-Si scaffolds occur for up to 2weeks, even in the absence of osteogenic supplements in the culture medium. The omission of media supplements to induce osteogenic differentiation is a promising feature towards simplified and cost-effective cell culturing procedures of a potential bioengineered product, and concomitant translation into the clinical field. Thus, the present work demonstrates that SPCL-Si scaffolds and their intrinsic properties sustain gBMSC osteogenic features in vitro, even in the absence of osteogenic supplements to the culture medium, and show great potential for bone regeneration strategies. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  5. Poly-L-arginine synergizes with oligodeoxynucleotides containing CpG-motifs (CpG-ODN) for enhanced and prolonged immune responses and prevents the CpG-ODN-induced systemic release of pro-inflammatory cytokines.

    PubMed

    Lingnau, Karen; Egyed, Alena; Schellack, Carola; Mattner, Frank; Buschle, Michael; Schmidt, Walter

    2002-10-04

    This study describes an entirely synthetic vaccine composed of antigenic peptides (T cell epitopes), oligodeoxynucleotides containing CpG-motifs (CpG-ODN) and poly-L-arginine (pR). CpG-ODN are known to be potent inducers of predominantly type 1-like immune responses, while polycationic amino acids, like pR, facilitate the uptake of antigens into antigen presenting cells (APCs). We demonstrate that the application of peptides and pR/CpG-ODN results in strongly enhanced peptide-specific immune responses as compared to the application of peptides with either of the immunomodulators alone. High numbers of antigen-specific T cells can be observed even after only one injection of the vaccine for a remarkably long period of time (at least 372 days). Furthermore, the potentially harmful systemic release of pro-inflammatory cytokines induced upon injection of CpG-ODN is inhibited. Thus, the combined application of CpG-ODN and pR may represent a novel vaccine strategy in humans.

  6. Eight Weeks of Phosphatidic Acid Supplementation in Conjunction with Resistance Training Does Not Differentially Affect Body Composition and Muscle Strength in Resistance-Trained Men

    PubMed Central

    Andre, Thomas L.; Gann, Joshua J.; McKinley-Barnard, Sarah K.; Song, Joon J.; Willoughby, Darryn S.

    2016-01-01

    not different between supplement groups. In response to eight weeks resistance training and PLC and PA (375 mg and 250 mg) supplementation, similar increases in muscle mass (RF CSA) occurred in all three groups; however, the increases were not different between supplement groups. Supplementation of PA in conjunction with RT does not impose a differential benefit; however, regarding trends in the data magnitude-based inferences indicate that PA has a more than likely impact on improving lower-body strength, whereas a likely impact for increasing muscle mass when combined with resistance training. PMID:27803633

  7. No differential effects of divergent isocaloric supplements on signaling for muscle protein turnover during recovery from muscle-damaging eccentric exercise.

    PubMed

    Rahbek, Stine Klejs; Farup, Jean; de Paoli, Frank; Vissing, Kristian

    2015-04-01

    Unaccustomed high-intensity eccentric exercise (ECC) can provoke muscle damage including several days of muscle force loss. Post-exercise dietary supplementation may provide a strategy to accelerate rate of force regain by affecting mechanisms related to muscle protein turnover. The aim of the current study was to investigate if protein signaling mechanisms involved in muscle protein turnover would be differentially affected by supplementation with either whey protein hydrolysate and carbohydrate (WPH+CHO) versus isocaloric carbohydrate (CHO) after muscle-damaging ECC. Twenty-four young healthy participants received either WPH+CHO (n = 12) or CHO supplements (n = 12) during post-exercise recovery from 150 maximal unilateral eccentric contractions. Prior to, at 3 h and at 24, 48, 96 and/or 168 h post-exercise, muscle strength, muscle soreness, and Akt-mTOR and FOXO signaling proteins, were measured in an ECC exercising leg and in the contralateral non-exercise control leg (CON). After ECC, muscle force decreased by 23-27 % at 24 h post-exercise, which was followed by gradual, although not full recovery at 168 h post-exercise, with no differences between supplement groups. Phosphorylation of mTOR, p70S6K and rpS6 increased and phosphorylation of FOXO1 and FOXO3 decreased in the ECC leg, with no differences between supplement groups. Phosphorylation changes were also observed for rpS6, FOXO1 and FOXO3a in the CON leg, suggesting occurrence of remote tissue effects. In conclusion, divergent dietary supplementation types did not produce differences in signaling for muscle turnover during recovery from muscle-damaging exercise.

  8. Application of a Salt Coformer in a Co-Amorphous Drug System Dramatically Enhances the Glass Transition Temperature: A Case Study of the Ternary System Carbamazepine, Citric Acid, and l-Arginine.

    PubMed

    Ueda, Hiroshi; Wu, Wenqi; Löbmann, Korbinian; Grohganz, Holger; Müllertz, Anette; Rades, Thomas

    2018-05-07

    The use of co-amorphous systems containing a combination of low molecular weight drugs and excipients is a relatively new technology in the pharmaceutical field to improve the solubility of poorly water-soluble drugs. However, some co-amorphous systems show a lower glass transition temperature ( T g ) than many of their polymeric solid dispersion counterparts. In this study, we aimed at designing a stable co-amorphous system with an elevated T g . Carbamazepine (CBM) and citric acid (CA) were employed as the model drug and the coformer, respectively. co-amorphous CBM-CA at a 1:1 molar ratio was formed by ball milling, but a transition from the glassy to the supercooled melt state was observed under ambient conditions, due to the relatively low T g of 38.8 °C of the co-amorphous system and moisture absorption. To improve the T g of the coformer, salt formation of a combination of l-arginine (ARG) with CA was studied. First, ball milling of CA-ARG at molar ratios of 1:1, 1:2, and 1:3 forming co-amorphous systems was performed and led to a dramatic enhancement of the T g , depending on the CA-ARG ratio. Salt formation between CA and ARG was observed by infrared spectroscopy. Next, ball milling of CBM-CA-ARG at molar ratios of 1:1:1, 1:1:2, and 1:1:3 resulted in co-amorphous blends, which had a single T g at 77.8, 105.3, and 127.8 °C, respectively. These ternary co-amorphous samples remained in a solid amorphous form for 2 months at 40 °C. From these results, it can be concluded that blending of the salt coformer with a drug is a promising strategy to design stable co-amorphous formulations.

  9. Development of a Transnasal Delivery System for Recombinant Human Growth Hormone (rhGH): Effects of the Concentration and Molecular Weight of Poly-L-arginine on the Nasal Absorption of rhGH in Rats.

    PubMed

    Kawashima, Ryo; Uchida, Masaki; Yamaki, Tsutomu; Ohtake, Kazuo; Hatanaka, Tomomi; Uchida, Hiroyuki; Ueda, Hideo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

    2016-01-01

    A novel system for delivering recombinant human growth hormone (rhGH) that is noninvasive and has a simple method of administration is strongly desired to improve the compliance of children. The aim of this study was to investigate the potential for the intranasal (i.n.) co-administration of rhGH with poly-L-arginine (PLA) as a novel delivery system by evaluating the effects of the concentration and molecular weight of PLA on the nasal absorption of rhGH. The influence of the formation of insoluble aggregates and a soluble complex in the dosage formulation on nasal rhGH absorption was also evaluated by size-exclusion chromatography and ultrafiltration. PLA enhanced the nasal absorption of rhGH at each concentration and molecular weight examined. Nasal rhGH absorption increased dramatically when the PLA concentration was 1.0 % (w/v) due to the improved solubility of rhGH in the formulation. A delay in rhGH absorption was observed when the molecular weight of PLA was increased. This appeared to be because the increase in molecular weight caused the formation of a soluble complex. It seems that the PLA concentration affects the absorption-enhancing effect on rhGH, while the molecular weight of PLA affects the time when the maximum plasma rhGH concentration was reached (Tmax) of rhGH after i.n. administration, mainly because of the interactions among rhGH, PLA, and additives. Therefore, the transnasal rhGH delivery system using PLA is considered to be a promising alternative to subcutaneous (s.c.) injection if these interactions are sufficiently controlled.

  10. Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with NG-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2.

    PubMed

    Jin, Li; Lin, Ming Quan; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Ryu, Yuhee; Sun, Simei; Kee, Hae Jin; Jeong, Myung Ho

    2017-07-01

    Gallic acid, a natural chemical found in plants, has been reported to show antioxidant, anticancer, and anti-inflammatory effects. We investigated the efficacy of a short-term or long-term treatment with gallic acid in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive mice and the underlying regulatory mechanism. Hypertension was sufficiently induced after 2 weeks of L-NAME administration. Cardiac remodeling was assessed by echocardiography. Hypertrophic markers, transcription factors, and fibrosis-related gene expression were evaluated by quantitative real-time polymerase chain reaction and western blotting. Gallic acid effectively lowered SBP, regardless of the administration route (intraperitoneal or oral). L-NAME increased the left ventricular (LV) thickness without an increase in the total heart weight. Weekly echocardiography demonstrated that gallic acid significantly reduced LV posterior wall and septum thickness in chronic L-NAME mice from 3 to 7 weeks. The administration of gallic acid to mice showed a dual preventive and therapeutic effect on the L-NAME-induced LV remodeling. The effect was associated with the suppression of the gene expression of hypertrophy markers and the GATA-binding factor 6 (GATA6) transcription factor. Short-term or long-term treatment with gallic acid attenuated cardiac fibrosis and reduced the expression of histone deacetylase 1 and 2 in H9c2 cells and in rat primary cardiac fibroblasts, as well as in vivo. Small interfering RNA knockdown confirmed the association of these enzymes with L-NAME-induced cardiac remodeling and fibrosis. These results suggested that gallic acid may be a potential therapeutic agent for the treatment of cardiovascular diseases with hypertension and cardiac fibrosis.

  11. Protective effects on vascular endothelial cell in N'-nitro-L-arginine (L-NNA)-induced hypertensive rats from the combination of effective components of Uncaria rhynchophylla and Semen Raphani.

    PubMed

    Li, Yunlun; Yang, Wenqing; Zhu, Qingjun; Yang, Jinguo; Wang, Zhen

    2015-08-01

    Endothelial dysfunction is closely associated with hypertension. Protection of vascular endothelial cell is the key to prevention and treatment of hypertension. Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid, isolated from traditional Chinese medicine Uncaria rbyncbopbylla and Semen Raphani respectively, exhibit properties of anti-hypertension and protection of blood vessels. In the present study, we observed the protective effect of the combined use of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid to the vascular endothelial cell in N'-nitro-L-arginine-induced hypertensive rats and investigate the preliminary mechanism. Blood pressure was detected by non-invasive rats tail method to observe the anti-hypertension effect of drugs. Scanning electron microscopy was used to observe the integrity or shedding state of vascular endothelial cell. The amount of circulating endothelial cells and CD54 and CD62P expression on circulating endothelial cells were tested to evaluate the endothelium function. In this study, we found that the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility can effectively lower the blood pressure, improve the structural integrity of vascular endothelium, and significantly reduce the number of circulating endothelial cells. Furthermore, the mean fluorescence intensity of CD54 and CD62P expressed showed decrease after the intervention of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility. In conclusion, the combination of effective components of the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid demonstrated good antihypertension effect and vascular endothelium protective effect. The preliminary mechanism of the protective effect may attribute to relieve the overall low-grade inflammation.

  12. Dietary betaine supplementation to gestational sows enhances hippocampal IGF2 expression in newborn piglets with modified DNA methylation of the differentially methylated regions.

    PubMed

    Li, Xi; Sun, Qinwei; Li, Xian; Cai, Demin; Sui, Shiyan; Jia, Yimin; Song, Haogang; Zhao, Ruqian

    2015-10-01

    The adequate supply of methyl donors is critical for the normal development of brain. The purpose of the present study was to investigate the effects of maternal betaine supplementation on hippocampal gene expression in neonatal piglets and to explore the possible mechanisms. Gestational sows were fed control or betaine-supplemented (3 g/kg) diets throughout the pregnancy. Immediately after birth, male piglets were killed, and the hippocampus was dissected for analyses. The mRNA abundance was determined by reverse transcription real-time polymerase chain reaction. Protein content was measured by Western blot, and DNA methylation was detected by methylated DNA immunoprecipitation assay. Prenatal betaine supplementation did not alter the body weight or the hippocampus weight, but increased the hippocampal DNA content as well as the mRNA expression of proliferation-related genes. Prenatal betaine supplementation increased serum level of methionine (P < 0.05) and up-regulated (P < 0.05) the mRNA and protein expression of betaine-homocysteine methyltransferase, glycine N-methyltransferase and DNA methyltransferase 1 in the neonatal hippocampus. Hippocampal expression of insulin growth factor II (IGF2) and its receptors IGF1R and IGF2R were all significantly up-regulated (P < 0.05) in betaine-treated group, together with a significant activation (P < 0.01) of the downstream extracellular signal-regulated kinase 1/2. Moreover, the differentially methylated region (DMR) 1 and 2 on IGF2 locus was found to be hypermethylated (P < 0.05) in the hippocampus of betaine-treated piglets. These results indicate that maternal betaine supplementation enhances betaine/methionine metabolism and DNA methyltransferase expression, causes hypermethylation of DMR on IGF2 gene, which was associated with augmented expression of IGF2 and cell proliferation/anti-apoptotic markers in the hippocampus of neonatal piglets.

  13. Differential Benefits of Attending Supplemental Instruction for Introductory, Large-Section, University U.S. History Courses

    ERIC Educational Resources Information Center

    Summers, Emily J.; Acee, Taylor W.; Ryser, Gail R.

    2015-01-01

    We investigated students' academic achievement in three high-enrollment, introductory-level history sections at a large, public, Hispanic-serving university. Using a conditional indirect-effects model, we analyzed supplemental instruction (SI) attendance and class absences as predictors of course success, after accounting for sex, ethnicity/race,…

  14. Determinants of DHA levels in early infancy: differential effects of breast milk and direct fish oil supplementation.

    PubMed

    Meldrum, S J; D'Vaz, N; Casadio, Y; Dunstan, J A; Niels Krogsgaard-Larsen, N; Simmer, K; Prescott, S L

    2012-06-01

    Although omega (n)-3 long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), intakes are important during infancy, the optimal method of increasing infant status remains unclear. We hypothesized that high-dose infant fish oil supplementation would have greater relative effects upon n-3 LCPUFA status at six months of age than breast milk fatty acids. Infants (n=420) were supplemented daily from birth to six months with fish oil or placebo. In a subset of infants, LCPUFA levels were measured in cord blood, breast milk and in infant blood at 6 months. DHA levels increased in the fish oil group relative to placebo (p<05). Breast milk DHA was the strongest predictor of infant erythrocyte DHA levels (p=<001). This remained significant after adjustment for cord blood DHA, supplementation group and adherence. In this cohort, breast milk DHA was a greater determinant of infant erythrocyte n-3 LCPUFA status, than direct supplementation with fish oil. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Prenatal choline supplementation alters the timing, emotion, and memory performance (TEMP) of adult male and female rats as indexed by differential reinforcement of low-rate schedule behavior

    PubMed Central

    Cheng, Ruey-Kuang; MacDonald, Christopher J.; Williams, Christina L.; Meck, Warren H.

    2008-01-01

    Choline availability in the maternal diet has a lasting effect on brain and behavior of the offspring. To further delineate the impact of early nutritional status, we examined effects of prenatal-choline supplementation on timing, emotion, and memory performance of adult male and female rats. Rats that were given sufficient choline (CON: 1.1 g/kg) or supplemental choline (SUP: 5.0 g/kg) during embryonic days (ED) 12–17 were trained with a differential reinforcement of low-rate (DRL) schedule that was gradually transitioned through 5-, 10-, 18-, 36-, and 72-sec criterion times. We observed that SUP-females emitted more reinforced responses than CON-females, which were more efficient than both groups of males. In addition, SUP-males and SUP-females exhibited a reduction in burst responding (response latencies <2 sec) compared with both groups of CON rats. Furthermore, despite a reduced level of burst responding, the SUP-males made more nonreinforced responses prior to the DRL criterion as a result of maintaining the previous DRL criterion following transition to a new criterion. In summary, long-lasting effects of prenatal-choline supplementation were exhibited by reduced frustrative DRL responding in conjunction with the persistence of temporal memory in SUP-males and enhanced temporal exploration and response efficiency in SUP-females. PMID:18323570

  16. Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice.

    PubMed

    Kelley, Christy M; Powers, Brian E; Velazquez, Ramon; Ash, Jessica A; Ginsberg, Stephen D; Strupp, Barbara J; Mufson, Elliott J

    2014-04-15

    Down syndrome (DS), trisomy 21, is a multifaceted condition marked by intellectual disability and early presentation of Alzheimer's disease (AD) neuropathological lesions including degeneration of the basal forebrain cholinergic neuron (BFCN) system. Although DS is diagnosable during gestation, there is no treatment option for expectant mothers or DS individuals. Using the Ts65Dn mouse model of DS that displays age-related degeneration of the BFCN system, we investigated the effects of maternal choline supplementation on the BFCN system in adult Ts65Dn mice and disomic (2N) littermates at 4.3-7.5 months of age. Ts65Dn dams were maintained on a choline-supplemented diet (5.1 g/kg choline chloride) or a control, unsupplemented diet with adequate amounts of choline (1 g/kg choline chloride) from conception until weaning of offspring; post weaning, offspring were fed the control diet. Mice were transcardially perfused with paraformaldehyde, and brains were sectioned and immunolabeled for choline acetyltransferase (ChAT) or p75-neurotrophin receptor (p75(NTR) ). BFCN number and size, the area of the regions, and the intensity of hippocampal labeling were determined. Ts65Dn-unsupplemented mice displayed region- and immunolabel-dependent increased BFCN number, larger areas, smaller BFCNs, and overall increased hippocampal ChAT intensity compared with 2N unsupplemented mice. These effects were partially normalized by maternal choline supplementation. Taken together, the results suggest a developmental imbalance in the Ts65Dn BFCN system. Early maternal-diet choline supplementation attenuates some of the genotype-dependent alterations in the BFCN system, suggesting this naturally occurring nutrient as a treatment option for pregnant mothers with knowledge that their offspring is trisomy 21. Copyright © 2013 Wiley Periodicals, Inc.

  17. Maternal choline supplementation differentially alters the basal forebrain cholinergic system of young-adult Ts65Dn and disomic mice

    PubMed Central

    Kelley, Christy M.; Powers, Brian E.; Velazquez, Ramon; Ash, Jessica A.; Ginsberg, Stephen D.; Strupp, Barbara J.; Mufson, Elliott J.

    2014-01-01

    Down syndrome (DS), trisomy 21, is a multifaceted condition marked by intellectual disability and early presentation of Alzheimer’s disease (AD) neuropathological lesions including degeneration of the basal forebrain cholinergic neuron (BFCN) system. While DS is diagnosable during gestation, there is no treatment option for expectant mothers or DS individuals. Using the Ts65Dn mouse model of DS that displays age-related degeneration of the BFCN system, we investigated the effects of maternal choline supplementation on the BFCN system in adult Ts65Dn mice and disomic (2N) littermates at 4.3–7.5 mos of age. Ts65Dn dams were maintained on a choline supplemented diet (5.1 g/kg choline chloride) or a control, unsupplemented diet with adequate amounts of choline (1 g/kg choline chloride) from conception until weaning of offspring; postweaning, offspring were fed the control diet. Mice were transcardially perfused with paraformaldehyde, brains were sectioned, and immunolabeled for choline acetyltransferase (ChAT) or p75-neurotrophin receptor (p75NTR). BFCN number and size, the area of the regions, and the intensity of hippocampal labeling were determined. Ts65Dn unsupplemented mice displayed region- and immunolabel-dependent increased BFCN number, larger areas, smaller BFCNs, and overall increased hippocampal ChAT intensity compared with 2N unsupplemented mice. These effects were partially normalized by maternal choline supplementation. Taken together, the results suggest a developmental imbalance in the Ts65Dn BFCN system. Early maternal-diet choline supplementation attenuates some of the genotype-dependent alterations in the BFCN system, suggesting this naturally occurring nutrient as a treatment option for pregnant mothers with knowledge that their offspring is trisomy 21. PMID:24178831

  18. Docosahexaenoic acid (DHA) supplementation in pregnancy differentially modulates arachidonic acid and DHA status across FADS genotypes in pregnancy.

    PubMed

    Scholtz, S A; Kerling, E H; Shaddy, D J; Li, S; Thodosoff, J M; Colombo, J; Carlson, S E

    2015-03-01

    Some FADS alleles are associated with lower DHA and ARA status assessed by the relative amount of arachidonic acid (ARA) and docosahexaenoic acid (DHA) in plasma and red blood cell (RBC) phospholipids (PL). We determined two FADS single nucleotide polymorphisms (SNPs) in a cohort of pregnant women and examined the relationship of FADS1rs174533 and FADS2rs174575 to DHA and ARA status before and after supplementation with 600mg per day of DHA. The 205 pregnant women studied were randomly assigned to placebo (mixed soy and corn oil) (n=96) or 600mg algal DHA (n=109) in 3 capsules per day for the last two trimesters of pregnancy. Women homozygous for the minor allele of FADS1rs174533 (but not FADS2rs174575) had lower DHA and ARA status at baseline. At delivery, minor allele homozygotes of FADS1rs174533 in the placebo group had lower RBC-DHA compared to major-allele carriers (P=0.031), while in the DHA-supplemented group, all genotypes had higher DHA status compared to baseline (P=0.001) and status did not differ by genotype (P=0.941). Surprisingly, DHA but not the placebo decreased ARA status of minor allele homozygotes of both FADS SNPs but not major allele homozygotes at delivery. Any physiological effects of changing the DHA to ARA ratio by increasing DHA intake appears to be greater in minor allele homozygotes of some FADS SNPs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Supplementation with RRR- or all-rac-α-Tocopherol Differentially Affects the α-Tocopherol Stereoisomer Profile in the Milk and Plasma of Lactating Women.

    PubMed

    Gaur, Shashank; Kuchan, Matthew J; Lai, Chron-Si; Jensen, Soren K; Sherry, Christina L

    2017-07-01

    Background: The naturally occurring α-tocopherol stereoisomer RRR- α-tocopherol is known to be more bioactive than synthetic α-tocopherol ( all-rac -α-tocopherol). However, the influence of this difference on the α-tocopherol stereoisomer profile of human milk is not understood. Objective: We investigated whether supplemental RRR- α-tocopherol or all-rac -α-tocopherol differentially affected the distribution of α-tocopherol stereoisomers in milk and plasma from lactating women. Methods: Eighty-nine lactating women aged 19-40 y and with a body mass index (in kg/m 2 ) ≤30 were randomly assigned at 4-6 wk postpartum to receive a daily supplement containing 45.5 mg all-rac -α-tocopherol acetate (ARAC), 22.8 mg all-rac -α-tocopherol acetate + 20.1 mg RRR -α-tocopherol (MIX), or 40.2 mg RRR- α-tocopherol (RRR). Milk and plasma were analyzed for α-tocopherol structural isomers and α-tocopherol stereoisomers at baseline and after 6 wk supplementation with the use of chiral HPLC. Results: There were no significant treatment group or time-dependent changes in milk or plasma α, γ, or δ-tocopherol. RRR- α-tocopherol was the most abundant stereoisomer in both milk and plasma in each group. Supplementation changed both milk and plasma percentage RRR- α-tocopherol (RRR > MIX > ARAC) ( P < 0.05) and percentage non- RRR- α-tocopherol (ARAC > MIX > RRR) ( P < 0.05). In the RRR group, percentage RRR- α-tocopherol increased in milk (mean ± SEM: 78% ± 2.3% compared with 82% ± 1.7%) ( P < 0.05) and plasma (mean ± SEM: 77% ± 1.8% compared with 87% ± 1%) ( P < 0.05). In contrast, the percentage RRR- α-tocopherol decreased in the MIX and ARAC groups (MIX, P < 0.05; ARAC, P < 0.0001), and percentage non- RRR- α-tocopherol stereoisomers increased (MIX, P < 0.05; ARAC, P < 0.0001) commensurate with an accumulation of 2S- α-tocopherol stereoisomers ( P < 0.05) in both milk and plasma. Milk and plasma RRR- α-tocopherol was positively correlated at baseline ( r

  20. Supplemental Citrulline Is More Efficient Than Arginine in Increasing Systemic Arginine Availability in Mice.

    PubMed

    Agarwal, Umang; Didelija, Inka C; Yuan, Yang; Wang, Xiaoying; Marini, Juan C

    2017-04-01

    Background: Arginine is considered to be an essential amino acid in various (patho)physiologic conditions of high demand. However, dietary arginine supplementation suffers from various drawbacks, including extensive first-pass extraction. Citrulline supplementation may be a better alternative than arginine, because its only fate in vivo is conversion into arginine. Objective: The goal of the present research was to determine the relative efficiency of arginine and citrulline supplementation to improve arginine availability. Methods: Six-week-old C57BL/6J male mice fitted with gastric catheters were adapted to 1 of 7 experimental diets for 2 wk. The basal diet contained 2.5 g l-arginine/kg, whereas the supplemented diets contained an additional 2.5, 7.5, and 12.5 g/kg diet of either l-arginine or l-citrulline. On the final day, after a 3-h food deprivation, mice were continuously infused intragastrically with an elemental diet similar to the dietary treatment, along with l-[ 13 C 6 ]arginine, to determine the splanchnic first-pass metabolism (FPM) of arginine. In addition, tracers were continuously infused intravenously to determine the fluxes and interconversions between citrulline and arginine. Linear regression slopes were compared to determine the relative efficiency of each supplement. Results: Whereas all the supplemented citrulline (105% ± 7% SEM) appeared in plasma and resulted in a marginal increase of 86% in arginine flux, supplemental arginine underwent an ∼70% FPM, indicating that only 30% of the supplemental arginine entered the peripheral circulation. However, supplemental arginine did not increase arginine flux. Both supplements linearly increased ( P < 0.01) plasma arginine concentration from 109 μmol/L for the basal diet to 159 and 214 μmol/L for the highest arginine and citrulline supplementation levels, respectively. However, supplemental citrulline increased arginine concentrations to a greater extent (35%, P < 0.01). Conclusions: Citrulline

  1. Supplemental Citrulline Is More Efficient Than Arginine in Increasing Systemic Arginine Availability in Mice123

    PubMed Central

    Agarwal, Umang; Didelija, Inka C; Yuan, Yang; Wang, Xiaoying; Marini, Juan C

    2017-01-01

    Background: Arginine is considered to be an essential amino acid in various (patho)physiologic conditions of high demand. However, dietary arginine supplementation suffers from various drawbacks, including extensive first-pass extraction. Citrulline supplementation may be a better alternative than arginine, because its only fate in vivo is conversion into arginine. Objective: The goal of the present research was to determine the relative efficiency of arginine and citrulline supplementation to improve arginine availability. Methods: Six-week-old C57BL/6J male mice fitted with gastric catheters were adapted to 1 of 7 experimental diets for 2 wk. The basal diet contained 2.5 g l-arginine/kg, whereas the supplemented diets contained an additional 2.5, 7.5, and 12.5 g/kg diet of either l-arginine or l-citrulline. On the final day, after a 3-h food deprivation, mice were continuously infused intragastrically with an elemental diet similar to the dietary treatment, along with l-[13C6]arginine, to determine the splanchnic first-pass metabolism (FPM) of arginine. In addition, tracers were continuously infused intravenously to determine the fluxes and interconversions between citrulline and arginine. Linear regression slopes were compared to determine the relative efficiency of each supplement. Results: Whereas all the supplemented citrulline (105% ± 7% SEM) appeared in plasma and resulted in a marginal increase of 86% in arginine flux, supplemental arginine underwent an ∼70% FPM, indicating that only 30% of the supplemental arginine entered the peripheral circulation. However, supplemental arginine did not increase arginine flux. Both supplements linearly increased (P < 0.01) plasma arginine concentration from 109 μmol/L for the basal diet to 159 and 214 μmol/L for the highest arginine and citrulline supplementation levels, respectively. However, supplemental citrulline increased arginine concentrations to a greater extent (35%, P < 0.01). Conclusions: Citrulline

  2. Water maze experience and prenatal choline supplementation differentially promote long-term hippocampal recovery from seizures in adulthood

    PubMed Central

    Wong-Goodrich, Sarah J.E.; Glenn, Melissa J.; Mellott, Tiffany J.; Liu, Yi B.; Blusztajn, Jan K.; Williams, Christina L.

    2010-01-01

    Status epilepticus (SE) in adulthood dramatically alters the hippocampus and produces spatial learning and memory deficits. Some factors, like environmental enrichment and exercise, may promote functional recovery from SE. Prenatal choline supplementation (SUP) also protects against spatial memory deficits observed shortly after SE in adulthood, and we have previously reported that SUP attenuates the neuropathological response to SE in the adult hippocampus just 16 days after SE. It is unknown whether SUP can ameliorate longer-term cognitive and neuropathological consequences of SE, whether repeatedly engaging the injured hippocampus in a cognitive task might facilitate recovery from SE, and whether our prophylactic prenatal dietary treatment would enable the injured hippocampus to more effectively benefit from cognitive rehabilitation. To address these issues, adult offspring from rat dams that received either a control (CON) or SUP diet on embryonic days 12–17 first received training on a place learning water maze task (WM) and were then administered saline or kainic acid (KA) to induce SE. Rats then either remained in their home cage, or received three additional WM sessions at 3, 6.5, and 10 weeks after SE to test spatial learning and memory retention. Eleven weeks after SE, the brains were analyzed for several hippocampal markers known to be altered by SE. SUP attenuated SE-induced spatial learning deficits and completely rescued spatial memory retention by 10 weeks post-SE. Repeated WM experience prevented SE-induced declines in glutamic acid decarboxylase (GAD) and dentate gyrus neurogenesis, and attenuated increased glial fibrilary acidic protein (GFAP) levels. Remarkably, SUP alone was similarly protective to an even greater extent, and SUP rats that were water maze trained after SE showed reduced hilar migration of newborn neurons. These findings suggest that prophylactic SUP is protective against the long-term cognitive and neuropathological effects of

  3. Addition of bone morphogenetic protein type 2 to ascorbate and β-glycerophosphate supplementation did not enhance osteogenic differentiation of human adipose-derived stem cells.

    PubMed

    Cruz, Ariadne Cristiane Cabral; Silva, Mariana Lúcia; Caon, Thiago; Simões, Cláudia Maria Oliveira

    2012-01-01

    Bone morphogenetic protein type 2 (BMP-2) is a potent local factor, which promotes bone formation and has been used as an osteogenic supplement for mesenchymal stem cells. This study evaluated the effect of a recombinant BMP-2 as well as the endogenous BMP-4 and BMP-7 in the osteogenic differentiation of adipose-derived stem cells (ASCs) in medium supplemented with ascorbate and β-glycerophosphate. Human ASCs were treated with osteogenic medium in the presence (ASCs+OM+BMP-2) or absence (ASCs+OM) of BMP-2. The alkaline phosphatase (ALP) activity was determined and the extracellular matrix mineralization was evaluated by Von Kossa staining and calcium quantification. The expressions of BMP-4, BMP-7, Smad1, Smad4, and phosphorylated Smad1/5/8 were analyzed by western blotting. Relative mRNA expressions of Smad1, BMP receptor type II (BMPR-II), osteonectin, and osteocalcin were evaluated by qPCR. ASCs+OM demonstrated the highest expression of BMP-4 and BMP-7 at days 21 and 7, respectively, the highest levels of BMPR-II mRNA expression at day 28, and the highest levels of Smad1 mRNA at days 14 and 28. ASCs+OM+BMP-2 demonstrated the highest levels of Smad1 mRNA expression at days 1, 7, and 21, the highest expression of Smad1 at day 7, the highest expression of Smad4 at day 14, the highest ALP activity at days 14 and 21, and expression of phosphorylated Smad1/5/8 at day 7. ASCs+OM and ASCs+OM+BMP2 showed similar ALP activity at days 7 and 28, similar osteonectin and osteocalcin mRNA expression at all time periods, and similar calcium depositions at all time periods. We concluded that human ASCs expressed endogenous BMP-4 and BMP-7. Moreover, the supplementation of ASCs with BMP-2 did not increase the level of osteogenic markers in the initial (ALP activity), intermediate (osteonectin and osteocalcin), or final (calcium deposition) phases, suggesting that the exogenous addition of BMP-2 did not improve the in vitro osteogenesis process of human ASCs.

  4. Addition of bone morphogenetic protein type 2 to ascorbate and β-glycerophosphate supplementation did not enhance osteogenic differentiation of human adipose-derived stem cells

    PubMed Central

    CRUZ, Ariadne Cristiane Cabral; SILVA, Mariana Lúcia; CAON, Thiago; SIMÕES, Cláudia Maria Oliveira

    2012-01-01

    Bone morphogenetic protein type 2 (BMP-2) is a potent local factor, which promotes bone formation and has been used as an osteogenic supplement for mesenchymal stem cells. Objectives This study evaluated the effect of a recombinant BMP-2 as well as the endogenous BMP-4 and BMP-7 in the osteogenic differentiation of adipose-derived stem cells (ASCs) in medium supplemented with ascorbate and β-glycerophosphate. Material and Methods Human ASCs were treated with osteogenic medium in the presence (ASCs+OM+BMP-2) or absence (ASCs+OM) of BMP-2. The alkaline phosphatase (ALP) activity was determined and the extracellular matrix mineralization was evaluated by Von Kossa staining and calcium quantification. The expressions of BMP-4, BMP-7, Smad1, Smad4, and phosphorylated Smad1/5/8 were analyzed by western blotting. Relative mRNA expressions of Smad1, BMP receptor type II (BMPR-II), osteonectin, and osteocalcin were evaluated by qPCR. Results: ASCs+OM demonstrated the highest expression of BMP-4 and BMP-7 at days 21 and 7, respectively, the highest levels of BMPR-II mRNA expression at day 28, and the highest levels of Smad1 mRNA at days 14 and 28. ASCs+OM+BMP-2 demonstrated the highest levels of Smad1 mRNA expression at days 1, 7, and 21, the highest expression of Smad1 at day 7, the highest expression of Smad4 at day 14, the highest ALP activity at days 14 and 21, and expression of phosphorylated Smad1/5/8 at day 7. ASCs+OM and ASCs+OM+BMP2 showed similar ALP activity at days 7 and 28, similar osteonectin and osteocalcin mRNA expression at all time periods, and similar calcium depositions at all time periods. Conclusions We concluded that human ASCs expressed endogenous BMP-4 and BMP-7. Moreover, the supplementation of ASCs with BMP-2 did not increase the level of osteogenic markers in the initial (ALP activity), intermediate (osteonectin and osteocalcin), or final (calcium deposition) phases, suggesting that the exogenous addition of BMP-2 did not improve the in vitro

  5. The Topology of the l-Arginine Exporter ArgO Conforms to an Nin-Cout Configuration in Escherichia coli: Requirement for the Cytoplasmic N-Terminal Domain, Functional Helical Interactions, and an Aspartate Pair for ArgO Function.

    PubMed

    Pathania, Amit; Gupta, Arvind Kumar; Dubey, Swati; Gopal, Balasubramanian; Sardesai, Abhijit A

    2016-12-01

    ArgO and LysE are members of the LysE family of exporter proteins and ordinarily mediate the export of l-arginine (Arg) in Escherichia coli and l-lysine (Lys) and Arg in Corynebacterium glutamicum, respectively. Under certain conditions, ArgO also mediates Lys export. To delineate the arrangement of ArgO in the cytoplasmic membrane of E. coli, we have employed a combination of cysteine accessibility in situ, alkaline phosphatase fusion reporters, and protein modeling to arrive at a topological model of ArgO. Our studies indicate that ArgO assumes an N in -C out configuration, potentially forming a five-transmembrane helix bundle flanked by a cytoplasmic N-terminal domain (NTD) comprising roughly its first 38 to 43 amino acyl residues and a short periplasmic C-terminal region (CTR). Mutagenesis studies indicate that the CTR, but not the NTD, is dispensable for ArgO function in vivo and that a pair of conserved aspartate residues, located near the opposing edges of the cytoplasmic membrane, may play a pivotal role in facilitating transmembrane Arg flux. Additional studies on amino acid substitutions that impair ArgO function in vivo and their derivatives bearing compensatory amino acid alterations indicate a role for intramolecular interactions in the Arg export mechanism, and some interactions are corroborated by normal-mode analyses. Lastly, our studies suggest that ArgO may exist as a monomer in vivo, thus highlighting the requirement for intramolecular interactions in ArgO, as opposed to interactions across multiple ArgO monomers, in the formation of an Arg-translocating conduit. The orthologous proteins LysE of C. glutamicum and ArgO of E. coli function as exporters of the basic amino acids l-arginine and l-lysine and the basic amino acid l-arginine, respectively, and LysE can functionally substitute for ArgO when expressed in E. coli Notwithstanding this functional equivalence, studies reported here show that ArgO possesses a membrane topology that is distinct

  6. The Topology of the l-Arginine Exporter ArgO Conforms to an Nin-Cout Configuration in Escherichia coli: Requirement for the Cytoplasmic N-Terminal Domain, Functional Helical Interactions, and an Aspartate Pair for ArgO Function

    PubMed Central

    Pathania, Amit; Gupta, Arvind Kumar; Dubey, Swati; Gopal, Balasubramanian

    2016-01-01

    ABSTRACT ArgO and LysE are members of the LysE family of exporter proteins and ordinarily mediate the export of l-arginine (Arg) in Escherichia coli and l-lysine (Lys) and Arg in Corynebacterium glutamicum, respectively. Under certain conditions, ArgO also mediates Lys export. To delineate the arrangement of ArgO in the cytoplasmic membrane of E. coli, we have employed a combination of cysteine accessibility in situ, alkaline phosphatase fusion reporters, and protein modeling to arrive at a topological model of ArgO. Our studies indicate that ArgO assumes an Nin-Cout configuration, potentially forming a five-transmembrane helix bundle flanked by a cytoplasmic N-terminal domain (NTD) comprising roughly its first 38 to 43 amino acyl residues and a short periplasmic C-terminal region (CTR). Mutagenesis studies indicate that the CTR, but not the NTD, is dispensable for ArgO function in vivo and that a pair of conserved aspartate residues, located near the opposing edges of the cytoplasmic membrane, may play a pivotal role in facilitating transmembrane Arg flux. Additional studies on amino acid substitutions that impair ArgO function in vivo and their derivatives bearing compensatory amino acid alterations indicate a role for intramolecular interactions in the Arg export mechanism, and some interactions are corroborated by normal-mode analyses. Lastly, our studies suggest that ArgO may exist as a monomer in vivo, thus highlighting the requirement for intramolecular interactions in ArgO, as opposed to interactions across multiple ArgO monomers, in the formation of an Arg-translocating conduit. IMPORTANCE The orthologous proteins LysE of C. glutamicum and ArgO of E. coli function as exporters of the basic amino acids l-arginine and l-lysine and the basic amino acid l-arginine, respectively, and LysE can functionally substitute for ArgO when expressed in E. coli. Notwithstanding this functional equivalence, studies reported here show that ArgO possesses a membrane topology

  7. Dietary Supplements

    MedlinePlus

    ... For Consumers Consumer Information by Audience For Women Dietary Supplements: Tips for Women Share Tweet Linkedin Pin it ... or 10877-382-4357. To Learn More about Dietary Supplements Information for Consumers on Using Dietary Supplements NIH ...

  8. Intestinal Barrier Function and the Gut Microbiome Are Differentially Affected in Mice Fed a Western-Style Diet or Drinking Water Supplemented with Fructose.

    PubMed

    Volynets, Valentina; Louis, Sandrine; Pretz, Dominik; Lang, Lisa; Ostaff, Maureen J; Wehkamp, Jan; Bischoff, Stephan C

    2017-05-01

    Background: The consumption of a Western-style diet (WSD) and high fructose intake are risk factors for metabolic diseases. The underlying mechanisms are largely unclear. Objective: To unravel the mechanisms by which a WSD and fructose promote metabolic disease, we investigated their effects on the gut microbiome and barrier function. Methods: Adult female C57BL/6J mice were fed a sugar- and fat-rich WSD or control diet (CD) for 12 wk and given access to tap water or fructose-supplemented water. The microbiota was analyzed with the use of 16S rRNA gene sequencing. Barrier function was studied with the use of permeability tests, and endo