L-arginine Supplementation Research Articles

Effect of l-arginine and l-lysine supplementation in low-protein feeds on the growth of native chickens in the starter phase

Some feeds that are used as protein sources, such as fish meal and soybean meal, have a relatively high cost. Therefore, synthetic amino acids, such as arginine and lysine, can be used as alternative protein sources. This study determined the effect of L-arginine and L-lysine in low-protein feed on the growth of one- to six-week-old native chickens. A total of 250 one-week-old native chickens were divided into five treatments and five replications based on a completely randomized design. The treatments were T-2 (0.46% L-arginine + 0.42% L-lysine + 19% crude protein), T-1 (0.56% L-arginine + 0.51% L-lysine + 18% crude protein), T0 (0.66% L-arginine + 0.60% L-lysine + 17% crude protein), T+1 (0.76% L-arginine + 0.69% L-lysine + 16% crude protein), and T+2 (0.86% L-arginine + 0.78% L-lysine + 15% crude protein). The highest feed consumption occurred in the T0 and T+1 treatments (612.81±4.82 and 609.00±8.75 g/chick), and the T+1 group had the highest body weight and weight gain (296.08±1.09 kg/chick and 265.48±1.57 g/chick). The highest carcass weight and percentage at T+1 was 177.57±2.04 g/chick and 59.97±0.55%/chick, respectively. The best feed conversion was at T+1 (2.29±0.40). Statistical analysis showed that the treatment had a significant effect on feed consumption, body weight, weight gain, feed conversion, carcass weight, and carcass weight percentage (P<0.05). The levels of 0.76% arginine + 0.69% lysine increased the feed consumption, weight gain, feed conversion, and carcass percentage of native chickens. The increase in L-arginine and L-lysine of 0.76 and 0.69% from 0.46 and 0.42%, respectively, suppressed the use of crude protein by 19.00% to 16.00% in the starter phase.

Putrescine supplementation shifts macrophage L-arginine metabolism related-genes reducing Leishmania amazonensis infection.

Leishmania is a protozoan that causes leishmaniasis, a neglected tropical disease with clinical manifestations classified as cutaneous, mucocutaneous, and visceral leishmaniasis. In the infection context, the parasite can modulate macrophage gene expression affecting the microbicidal activity and immune response. The metabolism of L-arginine into polyamines putrescine, spermidine, and spermine reduces nitric oxide (NO) production, favoring Leishmania survival. Here, we investigate the effect of supplementation with L-arginine and polyamines in infection of murine BALB/c macrophages by L. amazonensis and in the transcriptional regulation of genes involved in arginine metabolism and proinflammatory response. We showed a reduction in the percentage of infected macrophages upon putrescine supplementation compared to L-arginine, spermidine, and spermine supplementation. Unexpectedly, deprivation of L-arginine increased nitric oxide synthase (Nos2) gene expression without changes in NO production. Putrescine supplementation increased transcript levels of polyamine metabolism-related genes Arg2, ornithine decarboxylase (Odc1), Spermidine synthase (SpdS), and Spermine synthase (SpmS), but reduced Arg1 in L. amazonensis infected macrophages, while spermidine and spermine promoted opposite effects. Putrescine increased Nos2 expression without leading to NO production, while L-arginine plus spermine led to NO production in uninfected macrophages, suggesting that polyamines can induce NO production. Besides, L-arginine supplementation reduced Il-1b during infection, and L-arginine or L-arginine plus putrescine increased Mcp1 at 24h of infection, suggesting that polyamines availability can interfere with cytokine/chemokine production. Our data showed that putrescine shifts L-arginine-metabolism related-genes on BALB/c macrophages and affects infection by L. amazonensis.

Dietary Arginine and Citrulline Supplements for Cardiovascular Health and Athletic Performance: A Narrative Review.

The global market for nutritional supplements (NS) is growing rapidly, and the use of L-arginine (Arg), L-citrulline (Cit), and citrulline malate (CitMal) supplements has been shown to enhance cardiovascular health and athletic performance. Over the past decade, Arg, Cit, and CitMal supplements have received considerable attention from researchers in the field of exercise nutrition, who have investigated their potential effects on hemodynamic function, endothelial function, aerobic and anaerobic capacity, strength, power, and endurance. Previous studies were reviewed to determine the potential impact of Arg, Cit, and CitMal supplements on cardiovascular health and exercise performance. By synthesizing the existing literature, the study aimed to provide insight into the possible uses and limitations of these supplements for these purposes. The results showed that both recreational and trained athletes did not see improved physical performance or increased nitric oxide (NO) synthesis with 0.075 g or 6 g doses of Arg supplement per body weight. However, 2.4 to 6 g of Cit per day for 7 to 16 days of various NSs had a positive impact, increasing NO synthesis, enhancing athletic performance indicators, and reducing feelings of exertion. The effects of an 8 g acute dose of CitMal supplement were inconsistent, and more research is needed to determine its impact on muscle endurance performance. Based on the positive effects reported in previous studies, further testing is warranted in various populations that may benefit from nutritional supplements, including aerobic and anaerobic athletes, resistance-trained individuals, elderly people, and clinical populations, to determine the impact of different doses, timing of ingestion, and long-term and acute effects of Arg, Cit, and CitMal supplements on cardiovascular health and athletic performance.

Effects of dietary supplementation of tomato pomace (Solanum lycopersicum L.) and L-Arg on reproductive performance of aged male broiler breeders

This study aimed to investigate the effects of different dietary supplementation of tomato pomace (TP) and L-arginine (L-Arg) supplementation on sperm characteristics, reproductive performance, and semen biochemical components of aged commercial male broiler breeders. Thirty Ross 308 male broiler breeders (58 wk old) were provided and assigned to 5 dietary treatment groups, including control (CON), 5% TP (TPS-5), 10% TP (TPS-10), 15% TP (TPS-15), and L-Arg supplemented (10% above the recommendation, LAS-10). The results indicated that the semen volume increased in the TPS-15 group compared to that of the LAS-10 (and CON on wk 9) throughout the study (P < 0.05). The sperm concentration significantly increased in TPS-10 and TPS-15 groups in comparison to the other experimental groups. On wk 5 and 7, the sperm viability increased in all TPS groups compared to the CON and LAS-10, while on wk 9, it only increased in the TPS-10 group in comparison to the LAS-10 group (P < 0.05). The hypo-osmotic swelling test decreased in the LAS-10 group compared to the other experimental groups on wk 5 and all TPS groups on wk 7 and 9 (P < 0.05). The sperm total motility and forward progressive motility decreased in the LAS-10 group compared to the other experimental groups (P < 0.05). In contrast, unprogressive motility and immotile sperms were increased in the LAS-10 group compared to the other experimental groups (P < 0.05). In addition, the sperm penetration and fertility rate increased in TPS-10 and TPS-15 groups in comparison to CON and LAS-10 groups (P < 0.05). However, hatchability was reduced in the LAS-10 group (P < 0.05). The semen adenosine triphosphate increased in TPS-10, TPS-15, and LAS-10 groups compared to the CON (P < 0.05). Finally, the semen TAC and superoxidase dismutase decreased in the LAS-10 group (P < 0.05), while the glutathione peroxidase increased in the TPS-15 group (P < 0.05). In conclusion, 15% dietary TPS is recommended to improve the reproductive performance of aged commercial male broiler breeders.

L- Arginine and Nitric Oxide Levels Among Children with Sickle Cell Disease Presented With Vaso-Occlusive Crisis in Federal Teaching Hospital Gombe, North Eastern Nigeria.

Aim: The Aim of This Study Is To Evaluate The Level Of L- Arginine And Nitric Oxide Levels Among Children With Sickle Cell Disease presented with vaso-occlusive crisis in pediatric department, Federal Teaching Hospital Gombe, North Eastern Nigeria. Methology: The area selected for this study was Federal Teaching Hospital (FTH), Gombe, Nigeria. Gombe State is located in the North- estern part of Nigeria. This study included 60 children aged 1-14 years with a confirmed HbSS electrophoretic pattern presented to the sickle cell clinic unit of Federal Teaching Hospital Gombe, Gombe State. About 5 millilitres of blood sample was collected from each subject aseptically using the venepuncture technique. The blood was collected into tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA) anticoagulant and the remaining samples was left undisturbed at room temperature and later centrifuged at 3000rpm for 5minutes to obtain clear non- haemolysed plasma. The plasma was transferred into sterile labelled test tubes and assayed (in batches) for l-arginine and Nitric Oxide. Results: This study included children with a confirmed HbSS electrophoretic pattern aged 1-14 years with mean age 7.4500 ±0.50613 years, Presented to the sickle cell clinic unit of Federal Teaching Hospital Gombe, Gombe State. There was a statistically significant difference between the baseline and post L-arginine supplementation. The L-arginine and nitric oxide were significantly higher post supplementation compared to baseline levels among sickle cell disease subjects with vaso-occlusive crisis (p= 0.001and 0.01 respectively).

The Dark Side of an Essential Amino Acid: L-Arginine in Spinal Cord Injury.

L-arginine is a semi-essential amino acid involved in a variety of physiological processes in the central nervous system (CNS). It is essential in the survival and functionality of neuronal cells. Nonetheless, L-arginine also has a dark side; it potentiates neuroinflammation and nitric oxide (NO) production, leading to secondary damage. Therefore, modulating the L-arginine metabolism is challenging because both detrimental and beneficial effects are dependent on this semi-essential amino acid. After spinal cord injury (SCI), L-arginine plays a crucial role in trauma-induced neuroinflammation and regenerative processes via the two key enzymes: nitric oxide synthase (NOS) and arginase (ARG). Studies on L-arginine metabolism using ARG and NOS inhibitors highlighted the conflicting role of this semi-essential amino acid. Similarly, L-arginine supplementation resulted in both negative and positive outcomes after SCI. However, new data indicate that arginine depletion substantially improves spinal cord regeneration after injury. Here, we review the challenging characteristics of L-arginine metabolism as a therapeutic target after SCI.

Dietary L-arginine supplementation influences the muscle fiber characteristics and meat quality of Mongolian sheep through the NO/AMPK/PGC-1α pathway

L-arginine serves as a substrate for the production of nitric oxide (NO) in animals, and it can also impact muscle fiber characteristics and meat quality in these animals. The present study was designed to explore the effects of adding 1% L-arginine to a basal diet regimen on the muscle fiber characteristics and meat quality of Mongolian sheep. Dietary L-arginine supplementation reduced shear force in the longissimus thoracis (LT) and increased a* in biceps femoris (BF) muscles (p < 0.05). L-arginine supplementation also increased the proportion of type IIA muscle fiber in the LT (p < 0.05) and type I muscle fiber in the BF (p < 0.05) while reducing both the diameter and CSA of type IIB muscle fiber in both the LT and BF (CSA in LT, p < 0.01; all others, p < 0.05). L-arginine treatment was also associated with the upregulation of MyHC IIa (LT), MyHC I (BF), nNOS (LT & BF), AMPKα1 (BF), PGC-1α (LT & BF) (PGC-1α in BF, p < 0.01; all others, p < 0.05), together with an increase in nNOS content (LT, p < 0.01; BF, p < 0.05). Dietary L-arginine supplementation was associated with a significant increase in the post-slaughter tenderness of lamb meat, which is related to transitions in muscle fiber types. The gene expression and nNOS analysis results generated herein further indicate that this effect is mediated by the NO/AMPK/PGC-1α pathway. Further studies are thus warranted to provide further insight into the role that NO signaling plays in controlling the associations between L-arginine, muscle fiber characteristics, and meat quality.

Impact of L-Arginine and L-Glutamine supplementation on growth performance and immune status in weanling pigs challenged with Escherichia coli F4.

Arginine (ARG) and Glutamine (GLN) have been reported to play significant roles in protein metabolism, immunity, and intestinal health in weanling pigs. The present study investigated the independent and interactive effect of supplementing ARG and GLN on pigs immune status and growth performance following an Escherichia coli F4 challenge. A total of 240 mixed-sex pigs (24 ± 2 d old; 7.3 ± 0.1 kg BW) were used in a 42-d experiment after selection for E. coli F4 susceptibility. The pigs were group-housed (3 pigs per pen), and pens were randomly assigned to five experimental treatments (N = 16 pens per treatment). Experimental treatments were: 1) a wheat-barley-soybean meal-based basal diet (CTRL), 2) a basal diet with 2500 mg/kg zinc oxide (ZnO), 3) a basal diet + 0.5% Glutamine (0.5% GLN), 4) basal diet + 0.5% Arginine (0.5% ARG), and 5) basal diet with 0.5% Glutamine + 0.5% Arginine (0.5% GLN + ARG). All Pigs were inoculated with E. coli F4 on days 7, 8, and 9 post-weaning. Rectal swabs were taken from each pig and plated on blood agar plates for E. coli F4 presence. Blood and fecal samples were taken to determine the acute phase response and selected fecal biomarkers for the immune response. Growth performance and fecal scores were recorded. Fecal swabs resulted in no positive pig for E. coli F4 before inoculation and 73.3% positive postinoculation. Diarrhea incidence during days 7 to 14 was significantly lower for the ZnO treatment (P < 0.05). The haptoglobin level on day 3 was lower than days 10 and 20, irrespective of treatment (P < 0.05). The albumin level was lower on day 20 compared to days 3 and 10 (P < 0.05). There was no treatment effect on albumin levels regardless of sampling day (P > 0.05). The PigMAP was lowest on day 3 and highest on day 10 (P < 0.05). We did not observe significant treatment differences (P > 0.05) in myeloperoxidase and calprotectin. Pancreatitis-associated protein was higher in the ZnO (P = 0.001) treatment than in the other treatments. Fecal IgA tended (P = 0.10) to be higher in the ZnO and 0.5% ARG treatments. There were no performance differences, except during days 0 to 7, where the ZnO treatment was lower in average daily gain and average daily feed intake (P < 0.001), while feed efficiency (G:F) FE was similar across treatments. In summary, no improved performance was observed with either ARG, glutamate, or both. The immune response results showed that the E. coli F4 challenge may have exacerbated the acute phase response; hence, the benefits of dietary treatments did not go beyond immune repair and reduction in inflammation.

The Effects of an Acute Aerobic Exercise Session with L-arginine Supplementation on Selected Psychomotor and Physiological Parameters in Cyclists Recovered from COVID-19

Objective: The COVID-19 pandemic represents one of the major global crises of this century, bringing complications that can hinder the return to sport in infected athletes. Evidence suggests aerobic exercise and L-arginine supplementation may accelerate COVID-19 recovery. Hence, this study aimed to examine the effects of an acute aerobic exercise session with L-arginine supplementation on selected psychomotor and physiological parameters in cyclists recovered from COVID-19. Methods: Thirty-two male mountain bikers aged 18-25 years from Qazvin, Iran were randomized into four groups of eight: aerobic exercise + L-arginine supplementation, control, aerobic exercise + placebo, and L-arginine alone. Participants underwent pre- and post-testing surrounding an acute aerobic cycling session. The Shapiro-Wilk test assessed normality of data distribution. Analysis of covariance evaluated between-group differences. Statistical analyses were performed using SPSS version 26. Results: Analysis of covariance revealed significant between-group differences on psychomotor performance, maximal oxygen consumption, and peak anaerobic power variables (all p&lt;0.05). Post-hoc Bonferroni tests showed the aerobic exercise + L-arginine group had significantly greater improvements than aerobic + placebo and L-arginine groups (p&lt;0.05), with no differences between L-arginine and control. Conclusion: Aerobic exercise combined with L-arginine supplementation appears an effective strategy for enhancing psychomotor and physiological performance in cyclists recovered from COVID-19.

PS-B07-6: L-ARGININE SUPPLEMENTATION SUBSTANTIALLY ATTENUATES HYPERTENSION BUT NOT CARDIAC INJURY IN RATS WITH METABOLIC SYNDROME

Objective: L-arginine is not only a building block for protein but also a physiological substrate for the synthesis of nitric oxide (NO) and plays a regulatory role in signal transduction pathways in cells. Dietary L-arginine supplementation reduced fat mass both in Zucker diabetic fatty rats and in diet-induced obese rats. However, little is known about the effects of L-arginine on cardiac morphology and function in metabolic disorders. We have now examined the effects of L-arginine on cardiac pathology in DahlS.Z-Leprfa/Leprfa (DS/obese) rats, an animal model of metabolic syndrome (MetS). Design and method: DS/obese rats and their homozygous lean (DahlS.Z-Lepr+/Lepr+, or DS/lean) littermate controls were fed a purified control diet and were supplemented with 0.50% L-arginine-HCl or 0.85% L-alanine (isonitrogenous control) in drinking water from 13 to 17 weeks of age. Results: L-arginine supplementation did not affect body weight, visceral and subcutaneous fat mass, insulin resistance, or food and water intake in DS/obese rats, but substantially alleviated hypertension. However, left ventricular (LV) and cardiomyocyte hypertrophy and the upregulation of myocardial fetal-type gene expression, macrophage infiltration in the heart, and increased perivascular and interstitial fibrosis of the LV myocardium and the upregulation of fibrosis-related gene expression were not improved by such intervention. Additionally, L-arginine did not ameliorate impairments of Doppler- or micromanometer-derived indices of LV diastolic function. None of these parameters were influenced by L-arginine supplementation in DS/lean rats. Conclusions: L-arginine supplementation substantially ameliorated hypertension but did not attenuate LV remodeling or diastolic dysfunction in this model of MetS. These data suggest that in addition to its role as a precursor of NO, L-arginine may play a role as a functional amino acid that modulates growth and inflammation.

Aerobic exercise prevents cardiomyocyte damage caused by oxidative stress in early cardiovascular disease by increasing vascularity while L-arginine supplementation prevents it by increasing activation of the enzyme nitric oxide synthase.

L-Arginine and chronic exercise reduce oxidative stress. However, it is unclear how they affect cardiomyocytes during cardiovascular disease (CVD) development. The aim of this research was to investigate the possible effects of L-arginine supplementation and aerobic training on systemic oxidative stress and their consequences on cardiomyocytes during cardiometabolic disease onset caused by excess fructose. Wistar rats were allocated into four groups: control (C), fructose (F, 10% fructose in water), fructose training (FT; moderate running, 50-70% of the maximal velocity), and fructose arginine (FA; 880 mg/kg/day). Fructose was given for two weeks and fructose plus treatments for the subsequent eight weeks. Body composition, blood glucose, insulin, lipid profile, lipid peroxidation, nitrite, metalloproteinase-2 (MMP-2) activity, left ventricle histological changes, microRNA-126, -195, and -146, eNOS, p-eNOS, and TNF-α expressions were analyzed. Higher abdominal fat mass, triacylglycerol level, and insulin level were observed in the F group, and both treatments reversed these alterations. Myocardial vascularization was impaired in fructose-fed groups, except in FT. Cardiomyocyte hypertrophy was observed in all fructose-fed groups. TNF-α levels were higher in fructose-fed groups than in the C group, and p-eNOS levels were higher in the FA than in the C and F groups. Lipid peroxidation was higher in the F group than in the FT and C groups. During CVD onset, moderate aerobic exercise reduced lipid peroxidation, and both training and L-arginine prevented metabolic changes caused by excessive fructose. Myocardial vascularization was impaired by fructose, and cardiomyocyte hypertrophy appeared to be influenced by pro-inflammatory and oxidative environments.

Evaluation of dietary arginine supplementation to increase placental nutrient transporters in aged mares.

Nine pregnant mares (18.2 ± 0.7 yr; 493.82 ± 12.74 kg body weight [BW]) were used to test the hypothesis that dietary supplementation of l-arginine would enhance placental vascularity and nutrient transport throughout gestation in aged mares. Mares were balanced by age, BW, and stallion pairing, and assigned randomly to dietary treatments of either supplemental l-arginine (50 mg/kg BW; n = 7) or l-alanine (100 mg/kg BW; n = 6; isonitrogenous control). Mares were individually fed concentrate top-dressed with the respective amino acid treatment plus ad libitum access to Coastal Bermudagrass hay. Treatments began on day 14 of gestation and were terminated at parturition. Mare BW, body condition score (BCS), and rump fat were determined, and body fat percentage was calculated every 28 d and concentrate adjusted accordingly. Doppler blood flow measurements including resistance index (RI) and pulsatility index for uterine artery ipsilateral to the pregnant uterine horn were obtained beginning on day 21 and continued every 7 d until day 154 of gestation, and prior to parturition. Parturition was attended with foaling variables and placental measures recorded. Placental tissue from the pregnant horn was analyzed histologically to assess cell-specific localization of vascular endothelial growth factor (VEGF) and cationic amino acid transporter 1 (SLC7A1) proteins. Semiquantitative analyses were performed using 10 nonoverlapping images per sample fixed in a 10× field (Fiji ImageJ v1.2). Mare performance data were analyzed using PROC MIXED in SAS and foaling and placental data were analyzed using PROC GLM. Gestation length at parturition was not influenced (P > 0.05) by supplemental arginine. Compared with arginine-supplemented mares, control mares had a thicker rump fat layer (P < 0.01) and greater percent body fat (P = 0.03), and BCS (P < 0.01) at parturition. Arginine-supplemented mares had a lower RI than control mares prior to parturition (P < 0.01). Body length, height, and BW of foals at birth, as well as placental weight and volume, and immunohistochemical staining for VEGF and SLC7A1 at parturition, were not affected (P > 0.05) by maternal arginine supplementation. These results indicate that dietary arginine supplementation (50 mg/kg BW) is safe for gestating mares. A larger number of mares is required to extend knowledge of effects of supplemental arginine on embryonic/fetal survival and growth in mares.

Evidence-based interventions for reducing sickle cell disease-associated morbidity and mortality in sub-Saharan Africa: A scoping review.

Sickle cell disease is a lifelong illness affecting millions of people globally, but predominantly burdensome in sub-Saharan Africa, where most affected children do not live to adulthood, despite available evidence-based interventions that reduce the disease burden in high-income countries. We reviewed studies evaluating evidence-based interventions that decrease sickle cell disease-related morbidity and mortality among children living in sub-Saharan Africa. We used the Joanna Briggs scoping review methodological framework and grouped identified evidence-based interventions into preventative pharmacotherapeutic agents, newborn screening and comprehensive healthcare, disease-modifying agents, nutritional supplementation, systemic treatment, supportive agents and patient/carer/population education. We included 36 studies: 18 randomized controlled trials, 11 observational studies, 5 before-and-after studies and 2 economic evaluation studies, with most of the studies performed in West African countries. Included studies suggest evidence-based interventions effectively to reduce the common morbidities associated with sickle cell disease such as stroke, vaso-occlusive crisis, acute chest syndrome, severe anaemia and malaria infection. Evidence-based interventions also improve survival among study participants. Specifically, our review shows hydroxyurea increases haemoglobin and foetal haemoglobin levels, a finding with practical implications given the challenges with blood transfusion in this setting. The feasibility of implementing individual interventions is hampered by challenges such as affordability, accessibility and the availability of financial and human resources. Our review suggests that regular use of low-dose hydroxyurea therapy, sulphadoxine-pyrimethamine chemoprophylaxis, L-arginine and Omega-3 fatty acid supplementation and establishment of specialist stand-alone sickle cell clinics could reduce the sickle cell disease-associated morbidity and mortality in sub-Saharan Africa countries.

Exogenous L-arginine and light-emitting diode light supplementation to enhance growth, quality and antioxidant activity in green perilla microgreens

Exogenous L-arginine and light-emitting diode light supplementation to enhance growth, quality and antioxidant activity in green perilla microgreens

PS-C30-8: PREGNANT WOMEN WITH STRUGGLING WITH HIGH BLOOD PRESSURE IN PREGNANCY AND ROLE OF NITRIC OXIDE SUPPLEMENTS L-ARGININE FOR PROLONG PERIOD

Nitric oxide is a compound in the body to relax and widen blood vessels Some scientists believe that nitric oxide stimulates the release of certain hormones, such as insulin and human growth hormone. Researchers have performed multiple clinical trials related to nitric oxide supplements that includes L-citrulline and L-arginine and their effectiveness, often with mixed results. Taking nitric oxide supplements offers several heart boosting effects. Reducing arterial stiffness, blood pressure, and improving carotid artery blood flow, by enhancing blood flow in the body they improve performance in sports, promote healing, enhance heart health, and provide many other potential benefits. Preeclampsia, which is a form of high blood pressure that can occur in pregnancy, can be dangerous for both the woman and baby. A 2005 study in the European Journal of Clinical Investigation Trusted Source found that pregnant women who took L-arginine supplements for a prolonged period had lower blood pressure readings than pregnant women who did not take L-arginine. Although researchers need to conduct more studies, the results are promising for women struggling with high blood pressure in pregnancy. However, there are no studies that establish how much nitric oxide supplements people should take to achieve the results.

L-Arginine supplementation regulates energy-substrate metabolism in skeletal muscle and adipose tissue of diet-induced obese rats.

Dietary supplementation with l-arginine has been reported to reduce white fat mass in diet-induced obese rats and in obese humans. This study was conducted to test the hypothesis that the arginine treatment regulates glucose and fatty acid metabolism in insulin-sensitive tissues. Male Sprague-Dawley rats (4-week-old) were fed either low- or high-fat diets for 15 weeks (n = 16/diet). Thereafter, lean or obese rats were fed their respective diets and received drinking water containing either 1.51% l-arginine-HCl or 2.55% alanine (isonitrogenous control) (n = 8/treatment group). After 12 weeks of treatment, rats were euthanized and tissue samples were collected for biochemical assays. High-fat feeding increased the size of adipocytes isolated from retroperitoneal (RP) adipose tissue, while arginine treatment reduced their size. The total number of adipocytes in the adipose tissue did not differ among the four groups of rats. Glucose oxidation in extensor digitorum longus (EDL) muscle, soleus muscle, and RP adipose tissue were reduced in response to high-fat feeding. On the contrary, oleic acid oxidation in RP adipose tissue was enhanced in rats fed the high-fat diet. Arginine treatment stimulated both glucose and oleic acid oxidation in EDL and soleus muscles, while having no effect on glucose oxidation, oleic acid oxidation, or basal lipolysis per 106 adipocytes in RP adipose tissue. Collectively, these results indicate that oral supplementation with arginine to diet-induced obese rats promoted the oxidation of energy substrates in skeletal muscle, thereby reducing white fat in the body.

Dietary vasodilator and vitamin C/L-arginine/choline blend improve broiler feed efficiency during finishing and reduce woody breast severity at 6 and 7 wks

Woody breast has become a considerable economic concern to the poultry industry. This myopathy presents rigid, pale breasts characterized by replacement of lean muscle protein with connective tissue, a result of hypoxia and oxidative stress in a metabolically starved muscle with inadequate circulation. Hence, the objectives were to supplement broiler diets with ingredients specifically aimed to improve circulation and oxidative status. About 1,344 male Ross 708 broilers were assigned to 1 of 4 diets: 1) a basal diet (control), 2) basal diet plus a blend of 0.2% supplemental L-arginine, 0.17% choline bitartrate, and 0.03% vitamin C (blend), 3) 0.1% vasodilator ingredient (vasodilator), or 4) 0.02% Astaxanthin ingredient (AsX). At d 14, 28, 42, and 49, performance outcomes were collected on all birds and serum from 16 broilers/diet (n=64) was analyzed for creatine kinase and myoglobin. Once weekly beginning on d 28, a subset of 192 broilers were measured for breast width. On d 42 and 49, breast fillets from 16 broilers/diet (n=64) were palpated for woody breast severity, weighed, and analyzed for compression force at 1-day postmortem and water-holding capacity at 2-day postmortem. mRNA was isolated from 15 breast fillets/timepoint for qPCR quantification of myogenic gene expression. Data were analyzed using Proc Mixed (SAS Version 9.4) with the fixed effect of diet. Feed conversion ratio was improved in the blend and vasodilator-fed birds d 42 to 49, each by over 2 points (P < 0.05). Breast width was increased in the control on d 42 compared to the vasodilator and AsX-fed broilers (P < 0.05). At d 42, there were 12% greater normal fillets in blend diet-fed birds and 13% more normal scores in vasodilator-fed birds at d 49 compared to the control. At d 49, myogenin expression was upregulated in the AsX diet compared to blend and control diets (P < 0.05), and muscle regulatory factor-4 expression was increased by 6.5% in the vasodilator diet compared to the blend and AsX diets (P < 0.05). Blend and vasodilator diets simultaneously improved feed efficiency in birds approaching market weight while reducing woody breast severity.

L-Arginine supplementation enhanced expression of glucose transporter (GLUT 1) in sickle cell anaemia subjects in the steady state

L-Arginine may have therapeutic value in the management of sickle cell disease and diabetes mellitus. There is very little information on the interaction of GLUT 1 and L-Arginine in sickle cell disease subjects. This study compared the blood levels of Glut 1, fasting blood glucose (FBG) and fasting insulin (FIns) in non-sickle cell anaemia (HbAA) and sickle cell anaemia (HbSS) subjects in the steady state before and following L-Arginine supplementation (1 g/day for 6 weeks). Nitric oxide metabolites, (NOX), catalase, superoxide dismutase and glutathione peroxidase were also measured in each group of subjects. Correlation coefficients between change (Δ) in Glut 1 and change (Δ) in FBG, Fins, NOX and antioxidant enzymes respectively were calculated. Before supplementation, Glut 1, NOX, GPX and CAT were significantly higher in HbAA subjects while FIns, FBG and MDA were higher in HbSS subjects. In both groups, supplementation significantly increased NOX, Glut 1 and antioxidant enzymes but decreased MDA. Supplementation increased FIns in HbAA but decreased FBG and FIns in HbSS subjects. In both groups of subjects, ΔGLUT 1 correlated positively with ΔNOX, antioxidant enzymes and Δ[R] but negatively with ΔMDA. ΔGLUT 1 correlated negatively with ΔFBG and ΔFins in HbSS but positively in HbAA. Study thus showed that in the steady state HbSS subjects had lower GLUT 1 but elevated FBG and Fins levels than HbAA subjects. Additionally, L-Arginine increased GLUT I and antioxidant enzymes but decreased Fins, FBG and MDA in HbSS subjects.

Treatment optimization of the age-related cardiovascular and neurological pathology using known metabolic, cytoprotective, vasodilatory action substances. Review

Stressful situations that accompany us during military operations provoke a significant increase in the incidence of cardiovascular and psychoneurological pathology, especially among the elderly. Therefore, there is a need for a complex approach to treatment, in particular, with the use of combined drugs. The review presents data from preclinical and clinical studies on drugs with metabolic action - meldonium (trimethylhydrazinium propionate), L-arginine, and inosine. It has been shown that, apart from the general pharmacotherapeutic action, these drugs have a significant clinical effect on various illnesses in the form of adjunctive therapy. Antioxidant, neuroprotective, vasodilatory, and several pleiotropic effects of meldonium have been established. The use of meldonium as part of combined therapy improves the prognosis in cardiovascular and neurological disease treatment. Most reports ascribe the clinical benefits of L-arginine in cardiovascular diseases to the provision of NO. L-arginine is the only precursor for the NO-synthase reaction. NO is produced by all tissues of the body and plays particularly important roles in cardiovascular homeostasis. Very few articles examine the effects of L-arginine supplementation on central nervous system (CNS) function. However, accumulating evidence indicates that NO plays a role in memory formation. The possible role of L-arginine in Alzheimer's disease was investigated, taking into account the known functions of L-arginine in atherosclerosis, redox stress and inflammation, regulation of synaptic plasticity and neurogenesis, as well as modulation of glucose metabolism and insulin activity. Evidence is provided that L-arginine may play a prominent role in protecting against age-related degenerative diseases such as Alzheimer's disease. L-arginine has been demonstrated to improve peripheral circulation, renal function, and immune function. It also possesses anti-stress and adaptogenic capabilities. L-arginine stimulates the release of growth hormone as well as the release of pancreatic insulin and glucagon and pituitary prolactin. The antioxidant property of L-arginine has been well documented in several reports. As well known that inosenhancesance the myocardial energy potential improvesrove coronary circulation. At the same time over the past two decades, inosine has been shown to evoke significant improvements in motor function and visceral organ control in preclinical models of neurologic injury including spinal cord injury, stroke, traumatic brain injury, multiple sclerosis, and Parkinson`s disease through its ability to enhance the growth of axon collaterals from undamaged neurons. The basis of these beneficial effects stems from its antioxidant, anti-inflammatory, anxiogenic and neuroprotective properties. Keywords: age-related pathology; combined drugs; meldonium; L-arginine; inosine, endothelial dysfunction.

A modulatory effect of L-arginine supplementation on anticancer effects of chemoimmunotherapy in colon cancer-bearing aged mice.

Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are increased in cancer-bearing aged hosts. Arginase-I in MDSCs degrades L-arginine, an amino acid required for T cell activation and proliferation. In this study, we compared the therapeutic efficacy of 5-fluorouracil (5-FU)/oxaliplatin (L-OHP) and cyclophosphamide (CP) between young and aged colon cancer-bearing mice. Therapy with 5-FU/L-OHP and CP significantly suppressed the in vivo growth of CT26 and MC38 colon carcinomas in syngeneic young mice, whereas this effect was attenuated in aged mice. L-arginine monotherapy showed no effect in aged mice. However, additional therapy with anti-programmed cell death (PD)-1 antibody and L-arginine supplementation boosted the effect of chemoimmunotherapy in aged mice, and some mice were cured. During all combination therapy, tumor-specific cytotoxic T lymphocytes (CTLs) were generated from mice with non-progressing tumor, but not from those with progressing tumor. Plasma L-arginine levels were lower in aged than young mice, and chemotherapy tended to decrease the plasma L-arginine levels in aged mice. Compared to young mice, CT26-bearing aged mice decreased arginase activity, arginase-I expression, and the proportion of monocytic MDSCs in tumor tissues, whereas contrasting results were observed in MC38-bearing aged mice. Importantly, the induction of tumor-specific CTLs was impaired at lower doses of L-arginine in vitro, and the infiltration of CTLs into CT26 tissues after chemoimmunotherapy was promoted by L-arginine administration in vivo. These results indicate that chemoimmunotherapy was less effective in cancer-bearing aged mice, but that L-arginine supplementation can modulate its therapeutic efficacy via its effect on tumor-specific CTLs.