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The review summarises the data of the last 50 years on the effectiveness of the amino acid L-arginine in therapeutic practice in conditions accompanied by different-origin hypoxia. The aim of this review was to analyse the literature and our research data on the role of nitric oxide in the modulation of individual physiological reactivity to hypoxi...
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... the reaction to the effects of different-origin hypoxia (intense physical activity, acute stress, etc.) reflects the reserve compensatory capabilities of the body under the influence of extreme environmental factors [22,23,57]. Figure 3 presents the main mechanisms of responses to oxygen deficiency. ...
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... It has been demonstrated that supplementing with L-arginine increases NO production, strengthening antioxidant defenses [8]. In a number of illness models, it has been discovered that L-arginine lowers oxidative stress indicators such protein oxidation and lipid peroxidation [9]. By enhancing blood vessel function, lowering inflammation, and inhibiting platelet aggregation, L-arginine exerts cardioprotective effects [4]. ...
... Supplementation with L-arginine or its derivatives has shown promising results in reducing apoptosis and improving clinical outcomes in these conditions. The antiapoptotic properties of L-arginine have therapeutic implications in various diseases characterized by increased apoptosis, such as: Sepsis, Ischemia-reperfusion injury and Neurodegenerative disorders [9]. L-arginine metabolism can activate the Akt pathway, a signaling cascade that promotes cell survival and inhibits apoptosis [105]. ...
L-Arginine is an essential amino acid that plays a crucial role in various physiological processes. It serves as a precursor for nitric oxide (NO), which has potent antioxidant and anti-inflammatory properties. This review aims to comprehensively examine the medicinal importance of L-arginine as a natural antioxidant in preventing human health disorders. A comprehensive literature search was conducted using PubMed, Google Scholar, and other databases. Studies investigating the antioxidant effects of L-arginine and its potential role in preventing various diseases were included. L-Arginine has been shown to mediate NO production with strong antioxidant properties, scavenging free radicals and reducing oxidative stress. It has demonstrated therapeutic potential in preventing and mitigating various health conditions, including: Cardiovascular diseases, Neurodegenerative diseases, Metabolic disorders, Immune function and Anti-aging effects. L-Arginine is a potent natural antioxidant with significant medicinal importance. Its ability to scavenge free radicals, improve endothelial function, and support immune function makes it a promising therapeutic agent for preventing and treating a wide range of human health disorders. Further research is warranted to fully elucidate the mechanisms of action and optimal dosage for specific conditions.
... As a functional amino acid, L-arginine serves not only as a building block of protein but also as an essential substrate for the synthesis of nitric oxide (NO), creatine, polyamines, homoarginine. NO (a major vasodilator) increases blood flow to tissues and contributes to a moderate reduction of systolic (SBP) and diastolic blood pressure (DBP) [7,8]. ...
Background. Population aging has become a leading demographic feature of Ukraine. According to the World Health Organization, the number of elderly and senile people will increase to almost 40 % in the coming decades. Hypertension and type 2 diabetes mellitus (DM) are among the leading factors of cardiovascular risk. It is known that excessive oxidant stress and low-grade subclinical chronic systemic inflammation are determining factors of endothelial dysfunction, vascular reactivity disorders, increased peripheral vascular resistance, carbohydrate, and lipid metabolism disorders, which leads to increased blood pressure and plasma glucose levels. Hypertension and type 2 DM are among the leading cardiovascular risk factors. The purpose of the study was to increase the effectiveness of treatment and improve the quality of life of elderly patients with combined pathology of hypertension and type 2 DM by additional inclusion of empagliflozin and L-arginine in the basic therapy. Materials and methods. Fifty elderly patients with comorbid pathology were under our observation for second stage hypertension, coronary heart disease (functional class II) and type 2 DM in the stage of subcompensation. Participants were divided into two groups: the first one, controls (n = 25), received generally accepted basic therapy. In the second group (n = 25), the following drugs were added to the basic therapy: empagliflozin 10 mg/day, L-arginine 300 mg/day. Results. Clinical observation in outpatient conditions lasted for 3 months. Comprehensive therapy in the elderly patients with comorbid pathology of hypertension and type 2 diabetes, with the additional inclusion of empagliflozin and L-arginine to the basic therapy, contributes to a significant positive effect on the clinical course, reduces the risk of progression of this constellation. Conclusions. The application of the proposed comprehensive therapy in outpatient conditions under the control of a family doctor will significantly improve the quality of life of patients and prevent the development of complications
... Arginine has many functions in human physiology and pathology. Many disorders mediated by arginine and its metabolites have been intensively studied recently [63][64][65][66][67][68][69]. The equilibrium of arginine production in the human body by physiological adaption or by pharmacological therapies could be an efficient method for the prevention or treatment of L-arginine-NO pathway metabolic alteration-associated diseases [63][64][65][66][67][68][69]. ...
... Many disorders mediated by arginine and its metabolites have been intensively studied recently [63][64][65][66][67][68][69]. The equilibrium of arginine production in the human body by physiological adaption or by pharmacological therapies could be an efficient method for the prevention or treatment of L-arginine-NO pathway metabolic alteration-associated diseases [63][64][65][66][67][68][69]. ...
Recently, arginine has been proven to play an important role in ADPKD physiopathology. Arginine auxotrophy in ADPKD induces cell hyperproliferation, blocking the normal differentiation of renal tube cells and causing cyst formation. We explored the L-arginine (Arg)–nitric oxide (NO) molecular pathway in ADPKD, a multisystemic arginine auxotrophe disease. We developed a prospective case–control study that included a group of 62 ADPKD subjects with an estimated filtration rate over 60 mL/min/1.73 mp, 26 subjects with chronic kidney disease with an eGFR > 60 mL/min/1.73 mp, and a group of 37 healthy subjects. The laboratory determinations were the serum level of arginine, the enzymatic activity of arginase 2 and inducible nitric oxide synthase, the serum levels of the stable metabolites of nitric oxide (nitrate, direct nitrite, and total nitrite), and the endogenous inhibitors of nitric oxide synthesis (asymmetric dimethylarginine and symmetric dimethylarginine). In the ADPKD group, the levels of the arginine and nitric oxide metabolites were low, while the levels of the metabolization enzymes were higher compared to the control group. Statistical analysis of the correlations showed a positive association between the serum levels of Arg and the eGFR and a negative association between Arg and albuminuria. ADPKD is a metabolic kidney disease that is auxotrophic for arginine. Exploring arginine reprogramming and L-Arg–NO pathways could be an important element in the understanding of the pathogenesis and progression of ADPKD.
... This system, opposite to succinate, is driven by the activation of aminotransferase reactions, while inhibiting the activity of SDH under functional loads of varied nature (hypoxia, stress, etc.). On the other hand, exogenous AKG has cholinomimetic properties, exerting an effect on the ACh-cholinesterase system [134][135][136]. These two multidirectional systems are important for determining individual adaptation to low-oxygen conditions in the environment, which has been convincingly demonstrated in animals and humans with different levels of initial resistance to hypoxic and other loading [16][17][18]20,133,136]. ...
... On the other hand, exogenous AKG has cholinomimetic properties, exerting an effect on the ACh-cholinesterase system [134][135][136]. These two multidirectional systems are important for determining individual adaptation to low-oxygen conditions in the environment, which has been convincingly demonstrated in animals and humans with different levels of initial resistance to hypoxic and other loading [16][17][18]20,133,136]. ...
... Precisely these mechanisms of the formation of effective nitric oxide depots provide effective preconditions for increasing metabolic reserves during the physical training of older people and prevent the onset of cardiovascular pathologies. The relationship between nitric oxide and vascular pathologies in older adults has been convincingly demonstrated in a number of studies [20,136] and is shown in Figure 3. Physical activity in older people is important for maintaining the correct physiological ageing process [10]. ...
Anti-ageing biology and medicine programmes are a focus of genetics, molecular biology, immunology, endocrinology, nutrition, and therapy. This paper discusses metabolic therapies aimed at prolonging longevity and/or health. Individual components of these effects are postulated to be related to the energy supply by tricarboxylic acid (TCA) cycle intermediates and free radical production processes. This article presents several theories of ageing and clinical descriptions of the top markers of ageing, which define ageing in different categories; additionally, their interactions with age-related changes and diseases related to α-ketoglutarate (AKG) and succinate SC formation and metabolism in pathological states are explained. This review describes convincingly the differences in the mitochondrial characteristics of energy metabolism in animals, with different levels (high and low) of physiological reactivity of functional systems related to the state of different regulatory systems providing oxygen-dependent processes. Much attention is given to the crucial role of AKG and SC in the energy metabolism in cells related to amino acid synthesis, epigenetic regulation, cell stemness, and differentiation, as well as metabolism associated with the development of pathological conditions and, in particular, cancer cells. Another goal was to address the issue of ageing in terms of individual characteristics related to physiological reactivity. This review also demonstrated the role of the Krebs cycle as a key component of cellular energy and ageing, which is closely associated with the development of various age-related pathologies, such as cancer, type 2 diabetes, and cardiovascular or neurodegenerative diseases where the mTOR pathway plays a key role. This article provides postulates of postischaemic phenomena in an ageing organism and demonstrates the dependence of accelerated ageing and age-related pathology on the levels of AKG and SC in studies on different species (roundworm Caenorhabditis elegans, Drosophila, mice, and humans used as models). The findings suggest that this approach may also be useful to show that Krebs cycle metabolites may be involved in age-related abnormalities of the mitochondrial metabolism and may thus induce epigenetic reprogramming that contributes to the senile phenotype and degenerative diseases. The metabolism of these compounds is particularly important when considering ageing mechanisms connected with different levels of initial physiological reactivity and able to initiate individual programmed ageing, depending on the intensity of oxygen consumption, metabolic peculiarities, and behavioural reactions.
... Supplements containing arginine and citrulline may be safe for healthy individuals to consume when used cautiously and in accordance with a doctor's approval. When contemplating supplements, especially for those with health difficulties, it is critical to exercise caution and only purchase them from reputable vendors (Kurhaluk et al., 2023 andGrimble et al., 2007). ...
The use of nutritional supplements (NS) for improving sports performance and health has become popular, and Citrulline and Arginine are the most frequently used supplements in these fields. The global market for dietary supplements has had consistent growth in sales in the last decades. More than half of the individuals use dietary supplement extensively. Present systematic review aims to understand the role of dietary arginine and Citrulline supplements for cardiovascular health and sports performance. The complicated connection between the control of hemodynamic and overall homeostasis and Citrulline and Arginine have been established. Citrulline and Arginine play important role in protecting skeletal as well as health of cardiac muscles and structural integrity and also are involved in many metabolic processes. Arginine has successfully mediated the release of the synthesis of creatinine growth hormone, which significantly increases strength and muscle mass. Also, Arginine is necessary to produce nitric oxide, which promotes skeletal muscle growth and also enhances vascular function. Overall, arginine supplements have a reasonable positive effect on the health of the heart, muscles and bones, as well as on maintaining and escalate exercise capacity. On the other hand, Citrulline can possibly converted into Arginine in many cell types and can effectively make up shortages of Arginine and nitric oxide in various pathological and physiological circumstances. Moreover, Citrulline helps to detoxify ammonia while decreasing stress levels and fatigue and promoting performance of exercise. In order to increase and enhance human athletic activities, both arginine and Citrulline are required
... The other dominant amino acid in the present study was arginine. L-arginine is a nitric oxide (NO) precursor [81,82]. In the present study, the group of endogenous acids was dominated by glutamic and aspartic acids. ...
Raspberry fruits are an important source of many biologically active chemical compounds exerting nutritional and pro-health effects. The study presents a comparative analysis of nutritionally important bioactive chemical compounds—polyphenols; flavonoids, including anthocyanins; vitamin C; amino acids; fatty acids; and primary metabolites—contained in the fruits of three biennial fruiting cultivars, R. idaeus ‘Glen Ample’, ‘Laszka’, and ‘Radziejowa’, i.e., common cultivars in Poland and Europe. The antioxidant activity of fresh fruits and juice was determined with five methods. The analyses revealed the strong free radical scavenging potential of the fruits and juice, confirmed by the high concentration of nutrients, e.g., polyphenols, anthocyanins, vitamin C, amino acids, and fatty acids. The antioxidant activity of the juice determined with the ferric reducing antioxidant power (FRAP) and OH radical methods was from 2.5 to 4.0 times higher than that of the fruits. The following orders of total polyphenol contents were established in the analyzed cultivars: ‘Glen Ample’ < ‘Laszka’ < ‘Radziejowa’ in the fruits and ‘Glen Ample’ < ‘Radziejowa’ < ‘Laszka’ in the juice. The highest antioxidant activity was exhibited by the ‘Radziejowa’ fruits. Given their high content of dietary fiber, the fruits of the analyzed raspberry cultivars can be consumed by dieting subjects. The concentrations of vitamin C (28–34 mg/100 g) and anthocyanins (20–34 mg/100 g) indicate the biological and pharmacological activity of these fruits. The main unsaturated fatty acids in the fruits were gamma-linoleic acid (C18:2n6c) and alpha-linolenic acid (C18:3n3), which neutralize excess free radicals. The amino acids nutritionally essential to humans were dominated by leucine, arginine, and phenylalanine. This is the first comparative analysis of the antioxidant activity of fruits and juice and the contents of selected active compounds in the fruits of biennial fruiting cultivars of R. idaeus, i.e., a highly commercialized crop in Europe.
... The neurotoxic effects of arginine (Arg) and its metabolites, including guanidine compounds such as N-acetylarginine, homoarginine, and argic acid, are well known. In oxidative stress, an increase in Arg and its metabolites can lead to increased production of nitric oxide (NO), increased free radical levels, impaired antioxidant protection (due to decreased activity of superoxide dismutase and glutathione peroxidase), oxidation of proteins, and induction of lipid peroxidation in cell membranes [70,71]. Elevated levels of ROS prove to be one of the most critical factors contributing to neuronal cell death [72]. ...
A study was performed to determine early metabolomic markers of ischemic hypoxic encephalopathy (HIE) using a Rice–Vannucci model for newborn rats. Dried blood spots from 7-day-old male and female rat pups, including 10 HIE-affected animals and 16 control animals, were analyzed by liquid chromatography coupled with mass spectrometry (HPLC-MS) in positive and negative ion recording modes. Multivariate statistical analysis revealed two distinct clusters of metabolites in both HPLC-MS modes. Subsequent univariate statistical analysis identified 120 positive and 54 negative molecular ions that exhibited statistically significant change in concentration, with more than a 1.5-fold difference after HIE. In the HIE group, the concentrations of steroid hormones, saturated mono- and triglycerides, and phosphatidylcholines (PCs) were significantly decreased in positive mode. On the contrary, the concentration of unsaturated PCs was increased in the HIE group. Among negatively charged molecular ions, the greatest variations were found in the categories of phosphatidylcholines, phosphatidylinositols, and triglycerides. The major metabolic pathways associated with changed metabolites were analyzed for both modes. Metabolic pathways such as steroid biosynthesis and metabolism fatty acids were most affected. These results underscored the central role of glycerophospholipid metabolism in triggering systemic responses in HIE. Therefore, lipid biomarkers’ evaluation by targeted HPLC-MS research could be a promising approach for the early diagnosis of HIE.
... Вплив аргініну на базальний тонус був практично від сутнім (рис. 2,6,8). ...
... Додавання таурину (25 µmol/l) до перфузату з аргініном у разі нормаль ної оксигенації не призводило до змін активності серцевого м'яза (рис. 3,6,8). Тобто, таурин не впливав на ефек ти аргініну. ...
... В умовах депривації кисню (гіпок сія) негативний з точки зору функціо нування клітин вплив аргініну на Рис. 8 базальний тонус, який значно підви щувався майже до розвитку конт рактури, та різке зниження сили скорочення потребують додаткового пояснення. Відомо про неоднознач ність ролі системи NO у реалізації системних і локальних ефектів за гіпоксії [6]. Однак вважають, що NO має позитивну інотропну дію на ско ротливу здатність серцевого м'яза, особливо в умовах активації β 1 рецепторів [7]. ...
Добре відомо, що гіпоксія є універсальним чинником розвитку багатьох патологічних процесів, що так чи інакше призводить до зміни метаболічного забезпечення клітин з наступним порушенням їхніх функцій. Спрямована корекція таких патологічних змін є важливою в розумінні раціонального застосування комбінацій фармакологічних препаратів. З моменту вивчення визначальної ролі аргініну в утворенні оксиду азоту вважається, що сам по собі аргінін є корисним та абсолютно безпечним, але його багатогранний вплив на організм і клітини, особливо за умов нестачі кисню, вивчений не повністю.Мета дослідження – вивчити вплив аргініну та таурину на скоротливу активність серцевого м’яза щура в умовах нормальної та зниженої оксигенації й оцінити можливість використання комбінації цих двох сполук для корекції порушень скоротливої активності міокарда в умовах нестачі кисню.Дослідження було проведено на ізольованих смужках папілярних м’язів міокарда щурів. Смужки поміщали в експериментальну камеру та перфузували розчином Тироде. Для активації скорочень смужки папілярного м’яза міокарда використовували надпорогову польову стимуляцію електричними імпульсами прямокутної форми. Тривалість подразнюючих імпульсів складала 2,5–3,0 мс, амплітуда 15–20 В. Базова частота стимуляції складала 0,33 Гц.За умов нормальної оксигенації вплив аргініну на амплітуду скорочень ізольованого серцевого м’яза та його базальний тонус спостерігався у вигляді зниження амплітуди (сили) фазних скорочень, але був практично відсутнім його вплив на базальний тонус. Встановлено, що в умовах депривації кисню (гіпоксія) має місце помітне зниження амплітуди (сили) фазних скорочень серцевого м’яза та незначні коливання рівня базального тонусу. Встановлено, що за умов гіпоксії додавання в перфузат аргініну (100 μmol/l) призводить до розвитку вкрай небажаного різкого підвищення рівня тонічного напруження (базального тонусу) серцевого м’яза, що в умовах цілого організму може спровокувати стан зупинки серця в систолі. Важливо, що цей ефект повністю нівелювався при поєднаній дії аргі- ніну (100 μmol/l) та таурину (25 μmol/l), що підтверджує доцільність їхнього сумісного застосування в клінічній практиці.
... L-Arginine is a substrate for the production of nitric oxide (NO) via nitric oxide synthase (NOS). NO is a key signaling molecule in cardiovascular physiology and pathology, with negative chronotropic, negative, or positive inotropic effects, as well as positive gonadotropin effects [44,45]. NOS is a double-plus oxidase consisting of reductase and oxidase domains. ...
Augmented Renal Clearance (ARC) refers to the increased renal clearance of circulating solute in critically ill patients. In this study, the analytical research method of transcriptomics combined with metabolomics was used to study the pathogenesis of ARC at the transcriptional and metabolic levels. In transcriptomics, 534 samples from 5 datasets in the Gene Expression Omnibus database were analyzed and 834 differential genes associated with ARC were obtained. In metabolomics, we used Ultra-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry to determine the non-targeted metabolites of 102 samples after matching propensity scores, and obtained 45 differential metabolites associated with ARC. The results of the combined analysis showed that purine metabolism, arginine biosynthesis, and arachidonic acid metabolism were changed in patients with ARC. We speculate that the occurrence of ARC may be related to the alteration of renal blood perfusion by LTB4R, ARG1, ALOX5, arginine and prostaglandins E2 through inflammatory response, as well as the effects of CA4, PFKFB2, PFKFB3, PRKACB, NMDAR, glutamate and cAMP on renal capillary wall permeability.
Background/Aims: Important benefits of intermittent hypoxic training (IHT) have emerged as an effective tool for enhancing adaptive potential in different pathological states, among which acute hypoxia dominates. Therefore, the aim of our study was to evaluate the mechanisms related to the effects of the nitric oxide system (nitrites, nitrates, carbamide, and total polyamine content) on ADP-stimulated oxygen consumption and oxidative phosphorylation in heart and liver mitochondria and biomarkers of oxidative stress in the blood, heart, and liver of rats exposed to the IHT method and acute hypoxia and treated with the amino acid L-arginine (600 mg/kg, 30 min) or the NO synthase inhibitor L-NNA (35 mg/kg, 30 min) prior to each IHT session. Methods: We analysed the modulation of the system of oxygen-dependent processes (mitochondrial respiration with the oxygraphic method, microsomal oxidation, and lipoperoxidation processes using biochemical methods) in tissues during IHT in the formation of short-term and long-term effects (30, 60, and 180 days after the last IHT session) with simultaneous administration of L-arginine. In particular, we investigated how mitochondrial functions are modulated during intermittent hypoxia with the use of oxidation substrates (succinate or α-ketoglutarate) in bioenergetic mechanisms of cellular stability and adaptation. Results: The IHT method is associated with a significant increase in the production of endogenous nitric oxide measured by the levels of its stable metabolite, nitrite anion, in both plasma (almost 7-fold) and erythrocytes (more than 7-fold) of rats. The intensification of nitric oxide-dependent pathways of metabolic transformations in the energy supply processes in the heart and liver, accompanied by oscillatory mechanisms of adaptation in the interval mode, causes a probable decrease in the production of urea and polyamines in plasma and liver, but not in erythrocytes. The administration of L-arginine prior to the IHT sessions increased the level of the nitrite-reducing component of the nitric oxide cycle, which persisted for up to 180 days of the experiment. Conclusion: Thus, the efficacy of IHT and its nitrite-dependent component shown in this study is associated with the formation of long-term adaptive responses by preventing the intensification of lipoperoxidation processes in tissues due to pronounced changes in the main enzymes of antioxidant defence and stabilisation of erythrocyte membranes, which has a pronounced protective effect on the system of regulation of oxygen-dependent processes as a whole.
