L-arginine Group Research Articles

Mitigative Effects of l-Arginine and N-Acetyl Cysteine against Cisplatin-Induced Testicular Dysfunction and Toxicity through the Regulation of Antioxidant, Anti-inflammatory, and Antiapoptotic Markers: Role of miR-155 and miR-34c Expression.

Testicular dysfunction is a common adverse effect of cisplatin (CIS) administration as a chemotherapeutic drug. The current study has outlined the role of micro-RNAs (miR-155 and 34c) in CIS-induced testicular dysfunction and evaluated the protective effect of N-acetyl cysteine (NAC) and/or l-arginine (LA). Seven groups of Albino rats were used for this study. The control (C) group received physiological saline; the CIS group was injected CIS (7 mg/kg IP, once) on day 21 of the experiment; the NAC group was administered NAC (150 mg/kg intragastric, for 28 days); and the LA group was injected LA (50 mg/kg IP, for 28 days). NAC+CIS, LA+CIS, and NAC+LA+CIS groups received the above regime. CIS significantly reduced serum testosterone, LH, and FSH concentrations with decline of testicular enzyme activities. CIS caused significant elevation in testicular oxidative-stress biomarkers, inflammation-associated cytokines, and apoptosis markers, along with overexpression of miR-155 and low miR-34c expression. Additionally, marked testicular degenerative changes were observed in the examined histological section; a significant decrease in the expression of PCNA with significant increase in expressions of F4/80 and BAX was confirmed. The administration of NAC or LA upregulated testicular functions and improved histopathological and immunohistochemical changes as well as miRNA expression compared with the CIS-administered group. Rats receiving both NAC and LA showed a more significant ameliorative effect compared with groups receiving NAC or LA alone. In conclusion, NAC or LA showed an ameliorative effect against CIS-induced testicular toxicity and dysfunction through the regulation of antioxidant, anti-inflammatory, and antiapoptotic markers and via modulating miR-155 and miR-34c expression.

Determining the Effect of L-arginine and Physical Activity on the Plasma Levels of Endothelin-1 and Tissue Inhibitor of Metalloproteinase-1 in Postmenopausal Women with Hypertension

Background and Objectives Exercise and L-arginine supplementation are known as effective strategies for treating hypertension. The aim of the present study was to determine the effect of aerobic exercise and L-arginine consumption on tissue inhibitor of metalloproteinase-1 (TIMP-1) and endothelin-1 (ET-1) levels in postmenopausal women with hypertension. Subjects and Methods In this quasi-experimental research, 40 postmenopausal women with hypertension were divided into four equal groups including exercise, exercise + L-arginine, L-arginine, and placebo groups. Interventions of aerobic exercise (60-75% of maximum heart rate) and L-arginine supplementation (6 g/day) were completed for 12 weeks. Forty-eight hours after the last intervention session, blood samples similar to the pre-test were collected to measure TIMP-1 and ET-1 levels using ELISA method. Results Plasma ET-1 levels in the training and training + L-arginine groups were significantly reduced compared to the placebo and L-arginine groups. In addition, plasma TIMP-1 increased significantly in the exercise group and exercise + L-arginine group compared to the placebo group. No synergistic effect was observed on TIMP-1 and ET-1 levels, despite the greater effect of exercise combined with L-arginine supplementation. Conclusion According to the results of the present research, improved blood pressure in adaptation to aerobic exercises is associated with reduced ET-1 and increased TIMP-1. L-arginine supplement, either alone or in combination with aerobic exercise, has no significant effect on TIMP-1 and ET-1 changes.

Endurance training and L-arginine intake: Their effect on antioxidant indices in the heart muscles of rats.

Background: One of the side effects of doing sports activities is the increase of free radicals and oxidative stress. Aim: The present study aimed to investigate the effect of 8 weeks of increasing endurance training with L-arginine supplementation on oxidative indices in the cardiac organ of male Wistar rats. Methods: 32 male Wistar rats were divided into four groups control, L-arginine, endurance training, and L-arginine plus endurance training. Animals in the endurance training groups completed increasing endurance training on a motorized treadmill (60-min/session, 5 times/week) for 8 weeks. Animals in the L-arginine groups consumed an L-arginine solution daily (4 mg/kg/body weight). In the supplement group, L-arginine was given to the mice as a solution in water and as a gavage. Forty- eight hours after the last endurance training session, a heart tissue sample was taken and placed in an RNAlater liquid. Spectrophotometry and an ELISA kit were used to calculate the concentrations of glutathione peroxidase (GPX), malondialdehyde (MDA), and superoxide dismutase (SOD). Results: The present study showed that endurance training and L-arginine consumption did not affect SOD activity. L-arginine intake increased GPX. Endurance training caused a significant increase in MDA compared to the supplemented group (p = 0.01). Also, the consumption of L-arginine significantly increased the total antioxidant capacity TAC in the supplement group compared to the control group (p = 0.001). Conclusion: It seems that taking an L-arginine supplement can increase antioxidant enzymes.

Effect of adropin on seizure activity in rats with penicillin-induced epilepsy

BackgroundEpilepsy is a nervous system disease that affects millions of individuals worldwide, and up to 25% of patients have seizures that are resistant to antiepileptic drugs. Therefore, there is a need for the discovery of tolerable, effective antiepileptic agents. This study was aimed to electrophysiologically investigate the effects of the peptide hormone adropin, which was discovered in recent years and whose expression was determined in many organs, on penicillin-induced epileptiform activity in rats. MethodsForty 16–18 weeks old 280–300 g female Wistar albino rats were divided into 5 groups, 8 in each group. 250 min of ECoG recordings were taken from the first group only under anesthesia. Penicillin was given to the second group, L-arginine to the third group, adropin to the fourth group, and these three substances to the fifth group, and records were taken for 250 min and statistically evaluated. ResultsMeasurements were made as spike frequency, amplitude values, spike percent change, amplitude percent change. It was determined that the substances given on penicillin-induced acute epilepsy reduced both the number and severity of epileptic seizures. The lowest values were obtained from the L-arginine group, second from the mixture group, and third from the adropin group. ConclusionsAlthough the hormone adropin was not as effective as L-arginine on seizure activity, it can be said that it has a positive effect in terms of antiepileptic activity.

The Effect of L-Arginine Oral Supplementation on the Improvement of Cardiovascular Function and Pulmonary Artery Pressure in Patients with Major and Intermedia β-Thalassemia.

Thalassemia is the most common inherited anemia in worldwide. Heart failure is the most common cause of mortality and morbidity in patients with major and intermedia β-thalassemia. This study aimed to evaluate the effect of oral administration of L-arginine on the improvement of systolic Pulmonary Artery Pressure (PAP) and cardiac function in patients with major and intermedia β-thalassemia. This randomized clinical trial was done on 88 patients with β-thalassemia admitted to Ali Asghar Hospital, Tehran, Iran between 2020 and 2021. Echocardiography was performed for all the patients before the intervention. Afterwards, the patients were randomly divided into two groups of placebo and L-arginine. The patients underwent echocardiography after eight weeks and were compared with respect to the results. The mean blood transfusion interval was 20.21 d in the placebo group and 17.14 d in the L-arginine group (P=0.082). The results revealed no significant difference between the two groups regarding the mean levels of Hemoglobin (Hb) and ferritin, frequency of splenectomy. However, the mean PAP significantly decreased from 32.88 to 26.02 in the L-arginine group (P=0.009), but did not change in the placebo group. Nonetheless, no significant change was observed in the mean Ejection Fraction (EF) before and after L-arginine administration. L-arginine administration prevented the increase of PAP and was effective in preventing cardiovascular disorders including increased systolic PAP in patients with major and intermedia B-thalassemia. However, the results have to be confirmed in further studies with larger sample sizes.

Beneficial effects of L-Arginine in patients hospitalized for COVID-19: New insights from a randomized clinical trial

We have recently demonstrated in a double-blind randomized trial the beneficial effects of L-Arginine in patients hospitalized for COVID-19. We hypothesize that one of the mechanisms underlying the favorable effects of L-Arginine is its action on inflammatory cytokines. To verify our hypothesis, we measured longitudinal plasma levels of pro-inflammatory and anti-inflammatory cytokines implied in the pathophysiology of COVID-19 in patients randomized to receive oral L-Arginine or placebo. The study was successfully completed by 169 patients. Patients in the L-Arginine arm had a reduced respiratory support evaluated at 10 and 20 days; moreover, the time to hospital discharge was significantly shorter in the L-Arginine group. The assessment of circulating cytokines revealed that L-Arginine significantly reduced the circulating levels of pro-inflammatory IL-2, IL-6, and IFN-γ and increased the levels of the anti-inflammatory IL-10. Taken together, these findings indicate that adding L-Arginine to standard therapy in COVID-19 patients markedly reduces the need of respiratory support and the duration of in-hospital stay; moreover, L-Arginine significantly regulates circulating levels of pro-inflammatory and anti-inflammatory cytokines.

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<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<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.

Effect of pancreatin on acute pancreatitis resulting from L-arginine administration in mice, a morpho-histopathological and biochemical study

Acute pancreatitis (AP) is a life-unpleasant situation with contradictory and inadequate treatments. In this regard, the present study evaluated the effect of the possible pretreatment of lipase-pancreatin on L-arginine-induced AP. Forty adult mice were selected and divided into five groups: I) control group, II and III) AP groups (i.p.) receiving L-arginine of 2×300 and 2×400 mg/100 g body weight (b.w.), IV) AP (2×300 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase), and V) AP (2×400 L-arginine) group + pancreatin (mice were i.p. injected by 350 U-lipase). All AP groups displayed a significant increase in serum levels of ALT, AST, TBARS, and TNF-alpha compared to the control group. Moreover, pancreatic tissue edema, inflammation, and vacuolization of acinar cells were significantly higher in the untreated L-arginine group compared to the control and pancreatin groups. Conversely, the diameter of pancreatic islets significantly declined after induction of pancreatitis compared with control and pancreatin groups. Pancreatin treatment can be used in pancreatic dysfunction, however, this medicine showed no protective effect against L-arginine-induced AP in the mouse model.

Effects of NO, H2S and CO on Thiol/Disulfide Balance and Advanced Oxidation Protein Products in Hippocampus and Serum

Introduction: Nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO) are known as gaseous autocoids. It is not clear how the application of exogenous NO, H2S and CO alters the thiol/disulfide balance and advanced oxidation protein products (AOPPs) in the hippocampus and serum. Materials and Methods: In the study, rats were exogenously injected with L-arginine (100 mg/kg) as a NO donor, NaHS (10 mg/ kg) as a H2S donor, and CORM-2 (10 mg/kg) as a CO donor (II) (a tricarbonyldichlororuthenium dimer). Thiol/disulfide balance and advanced protein oxidation products were analyzed in hippocampus and serum samples. Results: The native thiol level in the hippocampus of the L-arginine group was statistically decreased compared to the native thiol level of the control group (p≤0.0001). The disulfide level in the hippocampus of the L-arginine group was statistically increased compared to the control group (p=0.009). Hippocampal total thiol level of NaHS group and CORM-2 group increased statistically (p=0.008,p=0.0157, respectively), while serum disulfide level of CORM-2 group decreased (p=0.0005). Serum and hippocampus AOPPs levels of the NaHS group were statistically increased compared to the control group (***p=0.0006, **p=0.0047, respectively). Similarly, the hippocampal AOPP level in the CORM-2 group was found to be statistically increased compared to the AOPP level in the control group (p=0.0437). Conclusion: As NaHS can improve thiol/disulfide balance, new studies are needed for CORM-2 and L-Arginine. This study is the first to report the effects of NO, H2S and CO on thiol/disulfide balance and AOPPs in the hippocampus and serum. Keywords: NO, H2S, CO, AOPPs, Thiol/disulfide

L-Arginine is a feasible supplement to heal chronic anal fissure via reducing internal anal sphincter pressure: a randomized clinical trial study.

The hypertonicity of internal anal sphincter resting pressure is one of the main causes of chronic anal fissure. Therefore, the aim of this study was to assess the effect of oral administration of L-arginine on the improvement of the anal fissures by relaxing the internal anal sphincter. Seventy-six chronic anal fissure patients (aged 18-65years) who were referred to Rasoul-e-Akram Hospital, Tehran, Iran from February 2019 to October 2020 participated in this randomized, double-blind, placebo-controlled trial. Participants were allocated into treatment (L-arginine) and placebo groups. They took a 1000mg capsule three times a day for 1 month, and then we followed them at the end of the first and third months after the intervention. Clinical symptoms, anal sphincter resting pressure, and quality of life (QoL) were completed at baseline and the end of the study. The analysis of data showed a significant decrease in bleeding, fissure size, and pain for each group; however, in the L-arginine group was more than the control group at the end of the study (P values < 0.001). Following that, a significant increase in QoL was seen just in patients treated with L-arginine (P value = 0.006). In addition, the comparison of anal pressures at baseline and, between groups at the end of the study showed a significant reduction in sphincter pressure in patients treated with L-arginine (P value < 0.001, = 0.049; respectively). The oral administration of 3000mg L-arginine can heal chronic anal fissures by reducing internal anal sphincter pressure with more negligible side effects. However, we recommend long-term study with more extended follow-up.Clinical trial registry: IRCT20190712044182N1 at Iranian clinical trials, date: 2019-08-27.

Hepatic Histopathological Alterations induced by L-Arginine and/or Dexamethasone in Adult Male Albino Rats

The liver is critical organ for metabolic homeostasis and toxic substance clearance and plays an important role in the systemic response to critical illness. Acute panreatitis (AP) progresses with a local production of inflammatory mediators, eventually leading to systemic inflammatory response syndrome. Knowing that almost all pancreatic mediators released from the pancreas to the blood stream may pass through the liver before their dilution in the systemic circulation, it would be reasonable to assume a determinant role of this organ in development of the inflammatory response associated with acute pancreatitis. Objectives: The study aimed to investigate the time courses of the effects of the exogenous glucocorticoids agonist dexamethasone on microscopical changes occurring in the liver of rats used as a model of AP induced by L-Arginine. Materials and Methods: 60 adult male albino rats weighing 150-200 gm were used. They were divided into 3 groups: Control group: Which is also divided into 2 subgroups (a &amp; b) each of animals of the first were IM injected with 0.5ml/100gm B.W saline and those of second were injected by 0.5mg/100gm B.W dexamethasone. L-Arginine group: which received L-Arginine to induce AP. The animals of this group were divided into 3 subgroups a, b and c the animals of which were sacrificed 3 days, 2 weeks and 1 month after L-Arginine injection respectively. Dexamethasone and L-Arginine group: in which the animals were injected with both L-Arginine and dexamethasone. They were also divided into 3 subgroups a, b and c, the animals of which were sacrificed 3 days. 2 weeks, one month after the injection of the drugs. The liver of the scarified animals were dissected out and prepared for microscopical examination. Results: The histopathological changes that occurred in the livers of acute pancreatitis (AP) model animals started in the periphery of the classic hepatic lobules and progressively extended in a centripetal manner to involve all the cells of the lobules in the late period of the experiment. These changes were in the form of ballooning of the hepatocytes, progressive vacuolation of their cytoplasm most propably with fat globules and depletion of the PAS+ve glycogen granules. Injection of dexamethasone in AP model animals did not improve the case, but on the contrary it made the changes more intense, severe, and rapid. One month after injection of L-Arginine and dexamethasone, the hepatocytes all over the hepatic lobules were severely affected. They were markedly ballooned with severely vacuolated cytoplasm which was completely depleted from its PAS +ve glycogen granules, indicating severe fatty degeneration of the liver. Conclusion: From the previous data, it can be concluded that treatment of AP with dexamethasone is caused a late bad effect on the liver, where it causes its late fatty liver changes.

Protective effects of L-arginine against aluminium chloride-induced testicular damage in rats.

Aluminium (Al) is a toxic metal with frequent exposure because it is a common element in nature and is found in many products used in daily life. L-arginine is a semi-essential amino acid that is involved in many biochemical pathways in the body and has antioxidant effects. The current research evaluated the possible protective effects of L-arginine against aluminium chloride (AlCl3 ) induced testicular damage. In this animal-based experimental study, 28 male Wistar Albino rats were separated into four groups: control, Al (20 mg/kg/day Al), Al + L-arginine (20 mg/kg/day Al + 50 mg/kg/day L-arginine), and L-arginine (50 mg/kg/day L-arginine). All applications were carried out intraperitoneally (i.p.) for 4 weeks. The histopathological changes caused by exposure to Al in the testicular tissue and the protective effects of L-arginine were investigated by using biochemical, histochemical, immunohistochemical [4-hydroxynonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG)] and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay techniques. The testicles in the AlCl3 group showed increased 4-HNE, 8-OHdG expressions, apoptotic index, and abnormal sperm content, while serum testosterone levels, sperm motility, and sperm number were decreased (p < 0.05). Furthermore, histomorphometric examinations of testicular tissue indicated significant structural impairments such as vacuolization in the seminiferous tubule epithelium, edema, and vascular congestion in the interstitial area (p < 0.05). However, the structural alterations were largely ameliorated in the Al + L-arginine group (p < 0.05). Thus, L-arginine, which is an antioxidant, may protect against the harmful effects of Al and may help improve male fertility.

Investigation of the Changes in Serum Intercellular and Vascular Adhesion Molecules (ICAM-1 and VCAM-1) and Nitric Oxide Levels in Response to Exercise Training and L-arginine Supplementation in Postmenopausal Hypertensive Women

Introduction: The positive effects of exercise training in modulating cardiovascular risk factors in individuals with hypertension have been reported. The present study aimed to investigate the effects of 8 weeks of combined training and L-arginine supplementation on the serum levels of intercellular and vascular adhesion molecules (ICAM-1 and VCAM-1) and nitric oxide (NO) in postmenopausal hypertensive women. Method: The postmenopausal women with hypertension were assigned into four groups consisting of 12 individuals, including placebo (P), L-arginine (L), training (T), and training+Larginine (TL) groups. The combined training program (resistance-endurance) was conducted 3 sessions per week for 8 weeks. The L-arginine ingestion was 6 g daily. Blood sampling was performed at the beginning and the end of 8 weeks of intervention, and the levels of ICAM-1, VCAM-1, and NO were measured. The collected data were analyzed in SPPSS software (version 24), one-way ANOVA, and Tukey post hoc test. Results: The levels of ICAM-1 and VCAM-1 in the T and TL groups compared to the P and L groups significantly decreased (P&lt;0.05). Significant increases of NO levels in the L (P=0.003), T (P&lt;0.001), and TL (P&lt;0.001) groups compared to the P group, and also a significant decrease in systolic and diastolic blood pressure were observed in all intervention groups in comparison to the P group (P&lt;0.05). Conclusion: Based on the findings of the present study, L-arginine ingestion and combined training alone or combined together are effective in the reduction of blood pressure in hypertensive patients. Moreover, L-arginine was associated with amplifying combined training effectiveness in decreasing systolic blood pressure. Blood pressure reduction in the above-mentioned groups is probably exerted partly by the upregulation of NO levels

Comparative evaluation of the effect of L-Arginine and L-Homoarginine supplementation on reproductive physiology in ewes

L-Arginine (LA) is a well-known amino acid involved in vital physiological processes. However, the physiological function of its methylated form known as L-Homoarginine (LHA), is not well understood. The aim of this study was to study the comparative effects of LA and LHA treatment on selected metabolites and parameters of reproductive physiology in non-pregnant ewes. Twelve Deccani ewes were selected and randomly distributed into 3 groups: Control, LA treated group and LHA group. Blood samples were collected for the evaluation of blood indices and hormone levels. Overall, nitrite, ovary weight, surface follicle number, estrogen, insulin like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF) showed an increase in the LA and LHA treated animals. On the other side, the levels of progesterone, inteleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α) were found to be decreased in LA and LHA group. Ovary size was not affected by LA and LHA treatment groups. In comparison with LA, the ovary weight, surface follicle number, estrogen levels and IL-6 expression were higher in LHA treated animals. The expression of VEGF indicated improved angiogenesis in the treated animals. Further, the expression of heat shock protein-27 (HSP-27) and HSP-70 were differentially modulated by LA and LHA. This data reinforces the beneficial role of LA and its metabolites LHA on the ovarian physiology and functionality and also reveals the potent role of LHA as an alternative to LA treatment in enhancing the reproductive ability in non-pregnant ewes.

Use of sildenafil and l-arginine in an experimental rat model for the prevention of neonatal necrotizing enterocolitis

Necrotizing enterocolitis (NEC) has a 45% mortality in neonatal intensive care units. This paper aimed to evaluate the isolated and combined effects of sildenafil and l-arginine in the prevention of necrotizing enterocolitis. Neonatal rats were fed formula milk and submitted to hypoxia under a 100% N2 atmosphere for 70 s. Then, animals were subjected to hypothermia (4 °C for 10 min), twice a day for 3 days. Forty neonatal rats were divided into five groups: negative control—not submitted to the protocol (n = 5), sildenafil group—NEC protocol (n = 9), l-arginine group—NEC protocol (n = 9), l-arginine and sildenafil group—NEC protocol (n = 9) and positive control—NEC protocol and intraperitoneal saline solution (n = 8). Jejunum and terminal ileus were removed for histopathologic and immunohistochemical Ki-67 analysis. Kruskal–Wallis test was used to analyze mortality, survival, body weight, intestinal injury score and Ki-67 proliferation index. All animals submitted to the protocol developed enterocolitis. Mortality rate was higher in group that received only l-arginine (p = 0.0293). The Ki-67 analysis showed a higher proliferative index in groups that received interventional drugs (p = 0.017). In conclusion, sildenafil and l-arginine were not effective to reduce intestinal injury.

L-Arginine Enhances the Effects of Cardiac Rehabilitation on Physical Performance: New Insights for Managing Cardiovascular Patients During the COVID-19 Pandemic.

Cardiac rehabilitation (CR) following acute myocardial infarction (AMI) improves physical capacities and decreases hospitalizations and cardiovascular mortality. L-arginine is the substrate used by nitric oxide (NO) synthase to generate NO and it has been shown to exert its beneficial effects on endothelium driving vasodilatation, reducing inflammation, and ameliorating physical function. We hypothesized that L-arginine could enhance physical capacities in patients who underwent CR after AMI. We designed a study aimed to assess the effects of L-arginine administration on the physical capacity of patients who underwent coronary revascularization after AMI. The trial was carried out amid the COVID-19 pandemic. Patients were assigned, with a 2:1 ratio, to add to their standard therapy one bottle containing 1.66 g of L-arginine or one bottle of identical aspect apart from not containing L-arginine, twice a day orally for 3 weeks. Patients performed a 6-minute walking test (6MWT), and their Borg modified 0-10 rating of perceived exertion (BRPE) was assessed before starting and at the end of the treatment. Seventy-five patients receiving L-arginine, and 35 receiving placebo successfully completed the study. The 6MWT distance increased significantly in the L-arginine group compared with both baseline and placebo (P < 0.0001). Additionally, we observed a significant improvement in the BRPE in patients treated with L-arginine but not in the placebo group. Taken together, our data indicate that L-arginine potentiates the response to CR independently of age, sex, baseline functional capacity, and comorbid conditions. SIGNIFICANCE STATEMENT: This study shows for the first time that oral supplementation of L-arginine potentiates the response to cardiac rehabilitation after myocardial infarction and cardiac revascularization. Indeed, we observed a significant improvement in two fundamental parameters, namely, the 6-minute walking test and the Borg modified 0-10 rating of perceived exertion. Strikingly, the beneficial effects of L-arginine were independent of age, sex, comorbid conditions, and baseline functional capacity.

Comparative Study of Metformin, N-Acetylcysteine and L-Arginine on Hyperglycemia in Streptozotocin-Induced Diabetic Rats

Diabetes mellitus (DM) is a chronic metabolic syndrome which results from deficiencies/defects in the pancreatic insulin secretions or insulin action on the target tissues. Purpose: To compare the beneficial effects of Metformin, N -acetylcysteine and L-arginine on dyslipidemia and hyperglycemia in Streptozotocin-induced diabetic rats. Study Design: Randomized controlled trial. Methodology: A total of 35 rats were used with 5 rats randomly allocated in 7 groups. Diabetic model was created by using streptozotocin (35 mg/kg) single dose intraperitoneal (IP). After 48 hours the animals with blood sugar concentration more than 300 mg/dl were considered diabetic. First group and second group were controls with Diabetic Mellitus (DM) rats. The group three, four and five with diabetic rats were given Metformin, N -acetylcysteine (NAC) and L-arginine (L-Arg) respectively. The sixth group of diabetic rats was given combination of Metformin and NAC while the seventh group of diabetic rats was given Metformin and L-Arg. All groups were treated for four weeks. At the end of the experimental period, groups were compared for fasting blood glucose. Statistical analysis: SPSS 25.0 statistical software was used to analyze the whole data. The difference between all the groups was analyzed using One-Way Analysis of Variance (ANOVA). Results: Significant improvement, with regards to the BSF test in L-Arginine Group, Metformin plus L-Arginine Group and the Metformin plus N-acetylcysteine group. Conclusion: It was concluded that in streptozotocin induced diabetic model, hyperglycaemia was significantly attenuated by the use of novel antioxidants; L-Arginine and N-acetylcysteine. Keywords: Hyperglycemia, L-arginine, Metformin, N-acetylcysteine and Streptozotocin.

Antioxidant and Neuroprotective Effects of L-arginine Administration After Traumatic Brain Injury and Hemorrhagic Shock in Rats.

To investigate the effect of fluid resuscitation and L-arginine administration on oxidant status markers, blood gases, lactate and apoptosis in the brain tissue of a rat model of TBI with hemorrhagic shock. A total of 60 rats were divided into six groups: control, isotonic saline-treated, 7.5% NaCl-treated (hypertonic saline), L-arginine-treated (100 mg/kg), saline + L-arginine-treated and 7.5% NaCl + L-arginine-treated groups. Closed head contusive weight-drop injuries were performed with hemorrhagic shock in all of the groups. Mean arterial pressure (MAP), pulse rate, lactate, malondialdehyde (MDA), total antioxidant capacity (TAC) and apoptosis were investigated. In a total of 48 rats, MAP levels remained higher than 60 mmHg for 3 hours in all of the treatment groups. The highest MAP values in each group were recorded. Higher MDA and lower TAC levels were observed in the control group than in all of the treatment groups (all p < 0.05). The number of apoptotic cells was highest in the control group and lowest in the L-arginine group. L-arginine administration may be an alternative treatment option for individualized fluid resuscitation in patients with TBI and hemorrhagic shock.

Role of l-arginine in the prevention of pre eclampsia in high-risk pregnancies.

Objective: To compare the efficacy of L-Arginine versus placebo in the prevention of pre eclampsia in high-risk pregnancies. Study Design: Randomized Control Trial. Setting: Department of Obstetrics and Gynecology, Nishtar Hospital Multan. Period: November 2019 to February 2019. Material &amp; Methods: A total of 130 women were included in the study. 65 patients were in L-arginine group or Group A while 65 patients were in placebo group or Group B. In group A, women were prescribed L-arginine 300 grams (Amino Whey Sachet) once a day until delivery and in group B; women were given homologated placebo (starch) once a day until delivery. Efficacy (no preeclampsia occurs during pregnancy) was noted from both groups and recorded. Mean ±SD was presented for quantitative variables like age, gestational age, parity, duration of chronic hypertension, weight, height and BMI. Variables such as age, parity, hypertension, body mass index, gestational age and duration of hypertension were stratified to assess their effect on efficacy. Chi square test was used to make comparison of the efficacy in both groups as well as for post-stratification for both groups. A p value of less than or equal to 0.05 was taken as significant. Results: In L-arginine group efficacy was 92.3% as compared to 69.2% in placebo group (p&lt; 0.000) Table-IV. Conclusion: It can be concluded that L-arginine when given orally at the dose of 300g daily has a considerable role in prevention of pre-eclampsia in pregnant patients with high risk and also has a role in reduction of severity of pre-eclampsia.

Effects of adding L-arginine orally to standard therapy in patients with COVID-19: A randomized, double-blind, placebo-controlled, parallel-group trial. Results of the first interim analysis.

BackgroundWe and others have previously demonstrated that the endothelium is a primary target of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and L-arginine has been shown to improve endothelial dysfunction. However, the effects of L-arginine have never been evaluated in coronavirus disease 2019 (COVID-19).MethodsThis is a parallel-group, double-blind, randomized, placebo-controlled trial conducted on patients hospitalized for severe COVID-19. Patients received 1.66 g L-arginine twice a day or placebo, administered orally. The primary efficacy endpoint was a reduction in respiratory support assessed 10 and 20 days after randomization. Secondary outcomes were the length of in-hospital stay, the time to normalization of lymphocyte number, and the time to obtain a negative real-time reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 on nasopharyngeal swab. This clinical trial had been registered at ClinicalTrials.gov, identifier: NCT04637906.FindingsWe present here the results of the initial interim analysis on the first 101 patients. No treatment-emergent serious adverse events were attributable to L-arginine. At 10-day evaluation, 71.1% of patients in the L-arginine arm and 44.4% in the placebo arm (p < 0.01) had the respiratory support reduced; however, a significant difference was not detected 20 days after randomization. Strikingly, patients treated with L-arginine exhibited a significantly reduced in-hospital stay vs placebo, with a median (interquartile range 25th,75th percentile) of 46 days (45,46) in the placebo group vs 25 days (21,26) in the L-arginine group (p < 0.0001); these findings were also confirmed after adjusting for potential confounders including age, duration of symptoms, comorbidities, D-dimer, as well as antiviral and anticoagulant treatments. The other secondary outcomes were not significantly different between groups.InterpretationIn this interim analysis, adding oral L-arginine to standard therapy in patients with severe COVID-19 significantly decreases the length of hospitalization and reduces the respiratory support at 10 but not at 20 days after starting the treatment.FundingBoth placebo and L-arginine were kindly provided by Farmaceutici Damor S.p.A., Naples