Protective Effects Of L-arginine Research Articles

Administration of combined exogenous L-arginine and ascorbic acid attenuates potassium bromate-induced renal and hepatic toxicity

Background: The use of potassium bromate (KBrO3) as food additive is still widespread and there is need to search for agents with protective effect against KBrO3-induced toxicity.
 Objective: In this study, the protective effects of L-arginine, ascorbic acid, and their combined regimen on KBrO3-induced renal and hepatic toxicity were investigated in Wistar rats.
 Methods: Five groups of male rats were used for the study. Group A was given distilled water (control), and group B was treated with KBrO3 only. In addition to KBrO3, groups C, D, and E were given L-arginine, ascorbic acid, and combined L-arginine and ascorbic acid respectively. After 28-day treatment, blood samples were taken for biochemical analysis; liver and kidney were harvested for histological examination.
 Results: KBrO3 significantly (p < 0.05) raised serum levels of creatinine, urea, ALT, and AST compared to distilled water-treated control. Levels of SOD, CAT, and GPx were also significantly reduced. No significant changes in these parameters were observed with ascorbic acid and L-arginine given separately. Treatment with combined regimen of L-arginine and ascorbic acid resulted in significant (p < 0.05) reduction in the serum levels of creatinine, AST and ALT, and significant increase in the serum levels of SOD, CAT and GPx compared to the control. The distortions induced by KBrO3 in the structural architecture of renal and hepatic tissues were largely reduced in rats treated with combined ascorbic acid and L-arginine.
 Conclusion: The study showed that L-arginine and ascorbic acid synergistically attenuate KBrO3-induced renal and hepatic toxicity.

Protective effects of L-arginine on Alzheimer's disease: Modulating hippocampal nitric oxide levels and memory deficits in aluminum chloride-induced rat model

There is evidence that high daily intake of aluminum (Al) is associated with an increased risk of dementia or cognitive decline. We injected L-arginine into the dorsal hippocampus (DH) of an AlCl3-induced Alzheimer's model and studied memory deficit, β-amyloid (βA) accumulation, neurodegeneration, and molecular changes. Male Wistar rats were cannulated unilaterally in the DH under a stereotaxic apparatus and a dose of AlCl3 (1–200 μg/rat) was injected into the CA1. After recovery, L-arginine and L-NAME (0.05–25 μg/rat) were injected into CA1 and animals were tested in novelty seeking task. One group received βA (2 μg/rat, intra CA1) as a reference group. Control groups received saline (1 μL/rat, intra-CA1) and galantamine (25 μg/rat, intra-CA1), respectively. Finally, rats were anesthetized and hippocampal tissues were isolated on ice. Levels of neuronal NO synthase (nNOS), β-secretase and soluble guanylyl cyclase (sGC) were measured by western blotting. βA formation and the number of CA1 neurons were assessed by Congo red and Nissl staining. NOS activation by NADPH-diaphorase (NADPH-d) was investigated. All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. Like βA, AlCl3 (25 μg/rat) caused accumulation of βA in the DH and increased stopping of the animal on the novel side (indicating a recall deficit). CA1 neurons decreased, and nNOS and β-secretase, but not sGC, showed a change consistent with Alzheimer's. However, prophylactic intervention of L-arginine at 3–9 μg/rat was protective, probably by nNOS stimulation in DH, as shown by NADPH-d assay. L-arginine may protect against Alzheimer's by increasing hippocampal NO levels.

Protective Effects of L-Arginine on Mitochondria of Rat Epididymis in Hyperhomocysteinemia Induced by Prolonged Methionine Load

INTRODUCTION: The study of markers of oxidative stress, metabolites of nitric oxide (II) (NOx) and the balance of carnitine fractions in mitochondria of rat epididymis, permits to evaluate the protective role of L-arginine in experimental hyperhomocysteinemia.
 AIM: To study the influence of L-arginine on the parameters of energy metabolism, level of NO metabolites, oxidative modification of proteins and balance of carnitine fractions in mitochondria of the head and tail of rat epididymis in hyperhomocysteinemia.
 MATERIALS AND METHODS: In animals of group 1 (n = 8), severe hyperhomocysteinemia (HHcy) was modeled by administration of methionine suspension at a dose of 1.5 g/kg twice daily for 21 days with addition of 1% methionine in drinking water; group 2 rats (n = 8) received suspension base without methionine; animals of group 3 (n = 8) were daily administered L-arginine solution at a dose of 500 mg/kg intragastrically against the background methionine load from day 11 to day 21; group 4 animals (n = 8) were administered L-arginine solution of at a dose of 500 mg/kg for 10 days; group 5 (n = 8) served as a control for group 4 and received drinking water intragastrically. Concentrations of total homocysteine and NOx were determined in serum. In the mitochondrial fraction of the homogenate of epididymis tissues, the level of oxidatively modified proteins (OMP), the concentration of NOx, lactate and carnitine fractions, the activity of lactate dehydrogenase (LDH), superoxide dismutase (SOD), H+-ATPase, succinate dehydrogenase (SDH) were evaluated.
 RESULTS: HHcy was accompanied by reduction of the level of NOx in blood serum and mitochondria of epididymis head tissues. In mitochondria of tissues of head and tail of epididymis, a marked reduction of all fractions of carnitine, activity of LDH, H+-ATPase, SDH, increase in the activity of SOD and in the level of OMP were observed. With modeled HHcy, L-arginine reduced the extent of hyperhomocysteinemia, prevented reduction of NOx level in the blood serum and epididymis head and reduced the content of OMP of the epididymis mitochondria.
 CONCLUSION: L-arginine introduced in combination with methionine, reduces the extent of severity of hyperhomocysteinemia. The positive effect of L-arginine on increase in the concentration of NOx metabolites in blood serum and mitochondria of epididymis in conditions of methionine load was also confirmed. L-arginine exhibits antioxidant properties, reducing the severity of oxidative stress induced by hyperhomocysteinemia. Differences in the adaptive response to oxidative stress of the mitochondria of the head and tail of epididymis were demonstrated.

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.

Protective effects of L-arginine on cognitive deficits and biochemical parameters in an experimental model of type-2 diabetes mellitus induced Alzheimer's disease in rats.

Alzheimer's disease (AD) has been closely linked to type 2 diabetes mellitus (T2DM) and insulin resistance plays a key role in the onset and development of AD. It has also been reported that NO donors play an important role in diabetes and have neuroprotective activity. The present study evaluated the effects NOS substrate, L-arginine and NOS-blocker, NG-nitro-L-arginine methyl ester (L-NAME) on cognitive functions, brain amyloid β levels and other associated biochemical markers in diabetes (T2DM)-induced AD in rats. T2DM was induced by a combination of high fat diet (HFD) and streptozotocin (STZ) (35 mg/kg, i.p.). Pretreatment with L-arginine (100 mg/kg/day) improved diabetes related biochemical parameters viz. plasma glucose, triglycerides and cholesterol. In addition, L-arginine also improved insulin levels and glucose tolerance. On the other hand, NO synthase inhibitor, L-NAME (10 mg/kg), did not have much influence on these parameters. Further, L-arginine treatment showed ameliorative effects on cognitive deficits seen in the Morris water maze (MWM) test when compared to the vehicle (saline) treated group and similar results were observed in the passive avoidance test. These neurobehavioural changes were associated with predictable modulations in Aβ levels in hippocampus and cortex in HFD + STZ + saline group, which were attenuated in the L-arginine, but not in the L-NAME-treated group. Our results indicate that L-arginine could be a considered a potential therapeutic strategy to attenuate the diabetes induced cognitive deficits in AD.

The Effects of L-Arginine and Nitric Oxide Donors on the Induction of Mitochondrial Permeability Transition Pore by Calcium Ions and Palmitoylcarnitine. Possible Involvement of Mitochondrial NO/cGMP/PKG Signaling System

This study was focused on the mechanisms of the protective effects of L-arginine and the nitric oxide donor SNAP under the induction of cyclosporine A-dependent mitochondrial permeability transition pore (MPTP) by excess of Ca2+ or D,L-palmitoylcarnitine (PC). The possible involvement of a signaling system that included mitochondrial enzymes NO-synthase (mtNOS), guanylate cyclase (GC), and cGMP-dependent protein kinase G (PKG) (mtNOS/GC/PKG-SS) in the regulation of MPTP was investigated. The experiments were performed on isolated liver mitochondria using inhibitory analysis. The results of the study have shown that L-arginine and SNAP caused a dose-dependent effects on the opening of MPTP. L‑Arginine and SNAP at low concentrations (5–100 μM) activated protective mechanisms, providing an increase in the mitochondrial calcium buffer capacity (CRC) and the critical (threshold) concentration of palmitoylcarnitine (PC*) required for MPTP induction. At higher concentrations, L-arginine (more than 500 μM) and SNAP (more than 100 μM) caused the opposite effect, that is, they suppressed respiration and promoted pore opening. Inhibitors of NOS, GC, and PKG eliminated the protective effects observed at low concentrations of L‑arginine and SNAP. The experiments conducted with a specific inhibitor of inducible NOS (W1400) showed that this calcium-independent enzyme did not participate in the regulation of MPTP in our experiments. Based on the results obtained, it can be assumed that the calcium-dependent mitochondrial signaling system mtNOS/GC/PKG-SS is involved in the regulation of MPTP, providing an increase in CRC and PC*. At high concentrations of L-arginine or SNAP, excess of NO overcame the protection provided by mtPKG and promoted pore opening.

Protective effects of l-arginine against testosterone synthesis decreased by T-2 toxin in mouse Leydig cells

The testosterone levels decreased by T-2 toxin in mouse Leydig cells were reported previously. It is not known, however, whether l-arginine improves the situation and what's the mechanism. Leydig cells were isolated and cultured with control, 10 nM T-2 toxin, 0.25, 0.5 or 1.0 mM l-arginine, and 10 nM T-2 toxin supplemented with 0.25, 0.5 or 1.0 mM l-arginine for 24 h. Cells and supernatants were collected to detect the mRNA expression and activities of P450scc (cholesterol side-chain cleavage enzyme), 3β-HSD-1 (3β-hydroxysteroid dehydrogenase/isomerase-1) and StAR (steroidogenic acute regulatory protein). Results revealed that l-arginine increased the testosterone levels declined by T-2 toxin and up-regulated the activities and mRNA expression of P450scc, 3β-HSD-1 and StAR down-regulated by T-2 toxin in Leydig cells. Therefore, we concluded that l-arginine ameliorated the testosterone levels decreased by T-2 Toxin via regulating the mRNA expression and activities of P450scc, 3β-HSD-1 and StAR in mouse Leydig cells.

Protective effect of L-arginine on gentamicin-induced nephrotoxicity in rats.

Introduction:L-arginine has a protective effect on gentamicin-induced renal failure and it may decrease the tubular reabsorption of another cationic substance, gentamicin due to its cationic structure. The aim of this study is to compare the possible protective effects of L-arginine and its inactive isomer D-arginine on gentamicin-induced nephrotoxicity in rats.Materials and Methods:Wistar albino rats were housed in metabolic cages and assigned to six groups as: control group, gentamicin (100 mg/kg), gentamicin + L-arginine (2 g/l), gentamicin + D-arginine (2 g/l), gentamicin + L-arginine + Nv-nitro-L-arginine methyl ester (L-NAME) (100 mg/l) and gentamicin + D-arginine + L-NAME. Gentamicin was administered by subcutaneous injections and the other drugs were added in drinking water for seven consecutive days. The animals were killed by decapitation and intracardiac blood and urine samples were obtained on the seventh day. Blood urea nitrogen, serum creatinine, sodium, potassium, urine gamma glutamyl transferase, creatinine, sodium, potassium and gentamicin levels were measured using High Performance Liquid Chromatography (HPLC) technique.Results:Gentamicin treated group had significant increase in blood urea nitrogen, serum creatinine, fractional Na excretion and urine gamma glutamyl transferase levels, and significant decrease in creatinine clearance compared to the control group. L-arginine and D-arginine reversed these findings. L-NAME abolished the nephroprotective effect of L-arginine. The urinary levels of gentamicin were significantly increased in rats treated with L-arginine or D-arginine compared to those treated with gentamicin. L-arginine and D-arginine reversed the advanced degenerative changes due to gentamicin administration in histopathological examination.Conclusion:Our study revealed the protective effect of L-arginine on gentamicin-induced nephrotoxicity, the contribution of the cationic feature of L-arginine, and the major role of NO in this protective effect.

The protective role of nitric oxide and nitric oxide synthases in whole-body hyperthermia-induced hepatic injury in rats

Purpose: The present study was designed to elucidate the role of endothelial nitric oxide (NO) synthase (eNOS), inducible NOS (iNOS)-derived NO and heat-shock protein (Hsp70) in a rat model of whole-body hyperthermia (WBH)-induced liver injury.Materials and methods: Real-time polymerase chain reaction, immunohistochemistry and western blot were used to observe the mRNA and protein expression of eNOS, iNOS and Hsp70. Rats were exposed to hyperthermia by immersion for 60 min at a conscious state in a water bath maintained at 41°C. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were used to assess liver injury 15 h after the hyperthermia challenge. Nitrosative and oxidative mediators, particularly NO and hydroxyl radical were measured.Results: Plasma AST, ALT, hydroxyl radical, and NO were significantly increased after WBH. There were 4.14 ± 0.42, 2.82 ± 0.34 and 2.91 ± 0.16-fold increases in the mRNA expression of eNOS, iNOS and Hsp70. Immunohistochemistry and western blot showed up-regulation of eNOS, iNOS and Hsp70 protein. An eNOS inhibitor (Nω-nitro-L-arginine methyl ester (L-NAME)), or an iNOS inhibitor (aminoguanidine (AG)), significantly aggravated the liver injury. On the contrary, administration of NO precursor, L-arginine (L-ARG), attenuated the liver injury. Hsp70 inhibitor quercetin reduced Hsp70, while aggravating the WBH-induced hepatic changes.Conclusions: WBH induces increases in eNOS, iNOS and Hsp70 expression with increase in NO release. The deleterious effects of L-NAME and AG and the protective effects of L-ARG and Hsp70 inhibitor on the liver function and pathology suggest that NO and heat shock protein play a beneficial role in the WBH-induced hepatic injury.

Curative and protective effects of l-arginine on carbon tetrachloride-induced hepatotoxicity in mice

l-arginine may aid in the liver detoxification and may benefit in the treatment of liver disorders such as liver injury. The present study was to investigate the possible protective and curative effects of l-arginine on carbon tetrachloride (CCl4) induced hepatotoxicity. Mice received a single dose of CCl4. l-arginine treatment was given for 6days prior or post to CCl4 injection. CCl4-intoxication caused marked liver cell necrosis with inflammatory and apoptotic lesions. l-arginine treatment reduced hepatic necrosis and inflammation. CCl4-intoxication also enhanced hepatic lipid peroxidation, decreased hepatic GSH level and inhibited the activities of antioxidant enzymes. Pre-treatment and post-treatment with l-arginine decreased lipid peroxidation and restored the antioxidant status to near normal levels. These results suggest that l-arginine administration has hepatoprotective and hepatocurative effects against CCl4 induced hepatotoxicity in mice.

Protective effects of L-Arginine in the diabetic vascular dysfunction

Objective To explore the effects of L-Arginine on diabetic vascular endothelial function. Methods 60 patients with Diabetes were randomly divided into two group:placebo control group(30 patients)and L-Arginine group(30 patients). Patients in L-Arginine group were taken L-Arginine 7g a day. All patients were treated for 28days and other 7days for elution. The plasma concentration of nitric oxide(NO) and endothelin (ET), vWF were measured in each group before and after the experiment. Flow Mediated Dilation(FMD) function of brachial artery of all patients were measured by high resolution vascular ultrasound. Results After the experiment, the plasma concentration of NO in L-Arginine group was higher than that of placebo group, meanwhile the plasma concentration of ET and vWF were lower than placebo group (P ＜ 0. 05). Moreover, FDM in L-Arginine group were significant higher than placebo group(P ＜ 0. 05). Conclusion L-Arginine could protect the vascular function in the diabetic patients. Key words: L-Arginine; Vascular function, diabetes

Protective effects of L-arginine on pulmonary oxidative stress and anti-oxidant defenses during exhaustive exercise in rats1

To assess the effects of L-arginine (L-Arg) supplementation on pulmonary oxidative stress and antioxidant defenses in rats after exhaustive exercise. Rats were randomly divided into four groups: sedentary control (SC), sedentary control with L-Arg treatment (SC+Arg), exhaustive exercise with control diet (E) and exhaustive exercise with L-Arg treatment (E+Arg). Rats in groups SC+Arg and E+Arg received a 2% L-Arg diet. Rats in groups E and E+Arg underwent an exhaustive running test on a motorized treadmill. Pulmonary oxidative stress indices [xanthine oxidase (XO), myeloperoxidase (MPO), and malondialdehyde (MDA)] and antioxidant defense systems [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione (GSH)] were investigated in this study. L-Arg supplementation significantly reduced exercise-induced elevations of XO and MPO activities in lung. L-Arg reversed the exercise-induced increase in SOD and GR activities, but increased CAT and GPX activities. L-Arg administration also significantly increased the GSH levels in plasma. L-Arg supplementation can prevent elevations of XO and MPO activities in the lung and favorably influence pulmonary antioxidant defense systems after exhaustive exercise.

The protective effects of L-arginine on the peripheral vascular functions in rabbits exposed to vibration

目的 探讨L-精氨酸对后肢接振家兔外周血管功能的保护作用及意义.方法将家兔随机分为单纯接振组(A组),L-精氨酸组(B组)和对照组(C组),并进行接振试验.从试验第11天起,每隔2d给予B组L-精氨酸20mg/kg,分别测定各组血浆一氧化氮(NO)、内皮素(ET)浓度进行测定分析.结果试验前及试验后第10天、20天、30天,A组NO浓度分别为(172.400±12.350)μmol/L、(167.915±7.879)μmol/L、(150.088±7.453)μmol/L、(132.313±8.747)μmol/L,ET浓度分别为(43.575±8.166)μg/L、(46.213±5.448)μg/L、(53.788±6.037)μg/L、(66.613±9.485)μg/L;B组浓度分别为(172.850±13.323)μmol/L、(167.788±10.531)μmol/L、(164.125±8.380)μmol/L、(161.813±7.639)μmol/L,ET浓度分别为(43.513±4.901)μg/L、(47.175±7.481)μg/L、(47.025±5.026)μg/L、(47.600±4.883)μg/L.随接振时间延长,A组NO浓度有明显降低、ET浓度有明显升高趋势(P<0.01);B组也有类似变化,但变化幅度较小. 结论 L-精氨酸可通过影响接振家兔血管内皮活性物质而保护外周血管功能。

Effect of Oral Administration of L-Arginine and L-Lysine on Lipid Metabolism against Isoproterenol-induced Myocardial Infarction in Rats

The protective effects of L-arginine in combination with L-lysine on lipid metabolism were examined against isoproterenol-induced myocardial infarction in rats. The levels of cholesterol, triacylglycerols and free fatty acids were estimated both in serum and the myocardial tissue.The levels of LDL- and HDL-cholesterol in serum and phospholipids in the myocardial tissues were also estimated in the normal and experimental rats. The rats administered isoproterenol (150mg kg-1 daily, intraperitoneally) showed significant changes in the lipid components. Prior oral treatment with L-arginine (250mg kg-1 daily) along with L-lysine (5mg kg-1 daily) in alleviating isoproterenol-induced biochemical disturbances with respect to lipid metabolism has been the hallmark of the study.

The role of the L-arginine/nitric oxide pathway in myocardial ischaemic and reperfusion injury.

Myocardial ischaemia followed by reperfusion (I/R) is associated with impaired endothelial function including diminished release and/or effects of nitric oxide (NO) which may contribute to the development of I/R injury. The aim of the present study was to investigate the role of the L-arginine/NO pathway in myocardial I/R injury. In isolated rat hearts subjected to global ischaemia followed by reperfusion L-arginine and the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP), but not D-arginine, significantly enhanced the recoveries of mycardial performance and coronary flow, and reduced the area of no-reflow and creatine kinase outflow. The NO synthase inhibitor NG-nitro-L-arginine (L-NNA) abolished the protective effects of L-arginine. Endothelium-dependent vasodilatation after I/R was preserved in L-arginine treated but not in vehicle hearts. Following I/R Ca2+-dependent NO synthase activity was reduced by 90% in comparison with non-ischaemic hearts. L-arginine but not D-arginine significantly increased NO synthase activity. In anaesthetized pigs, L-arginine given by local coronary venous retroinfusion reduced myocardial infarct size induced by 45 min of coronary artery ligation and 4 h of reperfusion to 35% of the area at risk from 76% in controls. The protective effect of L-arginine was blocked by L-NNA. Acetylcholine-induced coronary vasodilatation following I/R was attenuated in controls but not in L-arginine treated pigs. It is concluded that L-arginine or the NO donor SNAP reduces I/R-induced myocardial and endothelial injury. The protective effect of L-arginine seems to be mediated through maintained production of NO by preserving the function of Ca2+-dependent NO synthase in the heart.

Protective Effects of L-Arginine on Experimental Myocardial Injury Induced by .BETA.-Adrenergic Stimulation in Rats.

Changes in the activities of lysosomal enzymes (β-D-galactosidase, β-D-glucosidase, β-D-N-acetyl glucosaminidase, and β-fucosidase), mitochondrial enzymes (isocitrate dehydrogenase, malate dehydrogenase, succinate dehydrogenase, α-ketoglutarate dehydrogenase, and NADH dehydrogenase) and marker enzymes of cardiac function (LDH, AST, ALT, and CK) during isoproterenol-induced myocardial infarction and the effect of L-arginine pre-treatment were studied in male albino rats. In the rats given isoproterenol, there were significant increases in serum activities of LDH, CK, AST, and ALT and significant reductions in the myocardial tissue. Activity of the lysosomal enzyme β-D-N-acetyl glucosaminidase was considerably increased, and β-galactosidase was considerably decreased in the isoproterenol-treated rats as compared with that in those given isoproterenol after pre-treatment with L-arginine. The activities of the mitochondrial enzymes in the isoproterenol-intoxicated group were significantly lower as compared with those of the L-arginine supplemented rats given isoproterenol. These results confirm the efficacy of L-arginine as a potent cardioprotective agent and the protective effect of L-arginine against isoproterenol-induced mitochondrial and lysosomal damage.

The protective effects of L-arginine after liver ischaemia/reperfusion injury in a pig model

The protective effects of L-arginine after liver ischaemia/reperfusion injury in a pig model