Protective Effect Of Nitric Oxide Research Articles

Protective effect of nitric oxide on lettuce plants subjected to salt stress in semi-hydroponic system

Protective effect of nitric oxide on lettuce plants subjected to salt stress in semi-hydroponic system

Alpha Globin Gene Copy Number Is Associated with Prevalent Chronic Kidney Disease and Incident End-Stage Kidney Disease among Black Americans.

α-Globin is expressed in endothelial cells of resistance arteries, where it limits endothelial nitric oxide signaling and enhances α-adrenergic-mediated vasoconstriction. α-Globin gene (HBA) copy number is variable in people of African descent and other populations worldwide. Given the protective effect of nitric oxide in the kidney, we hypothesized that HBA copy number would be associated with kidney disease risk. Community-dwelling Black Americans aged ≥45 years old were enrolled in a national longitudinal cohort from 2003 through 2007. HBA copy number was measured using droplet digital PCR. The prevalence ratio (PR) of CKD and the relative risk (RR) of incident reduced eGFR were calculated using modified Poisson multivariable regression. The hazard ratio (HR) of incident ESKD was calculated using Cox proportional hazards multivariable regression. Among 9908 participants, HBA copy number varied from 2 to 6. In analyses adjusted for demographic, clinical, and genetic risk factors, a one-copy increase in HBA was associated with 14% greater prevalence of CKD (PR, 1.14; 95% CI, 1.07 to 1.21; P<0.0001). While HBA copy number was not associated with incident reduced eGFR (RR, 1.06; 95% CI, 0.94 to 1.19; P=0.38), the hazard of incident ESKD was 32% higher for each additional copy of HBA (HR, 1.32; 95% CI, 1.09 to 1.61; P=0.005). Increasing HBA copy number was associated with a greater prevalence of CKD and incidence of ESKD in a national longitudinal cohort of Black Americans.

Role of Nitric Oxide and Protein S-Nitrosylation in Ischemia-Reperfusion Injury.

Ischemia-reperfusion injury (IRI) is a process in which damage is induced in hypoxic tissue when oxygen supply is resumed after ischemia. During IRI, restoration of reduced nitric oxide (NO) levels may alleviate reperfusion injury in ischemic organs. The protective mechanism of NO is due to anti-inflammatory effects, antioxidant effects, and the regulation of cell signaling pathways. On the other hand, it is generally known that S-nitrosylation (SNO) mediates the detrimental or protective effect of NO depending on the action of the nitrosylated target protein, and this is also applied in the IRI process. In this review, the effect of each change of NO and SNO during the IRI process was investigated.

Nitric oxide restores peripheral blood mononuclear cell adhesion against hypoxia via NO-cGMP signalling.

Hypoxia is the most detrimental threat to humans residing at high altitudes, affecting multifaceted cellular responses that are crucial for normal homeostasis. Inhalation of nitric oxide has been successfully implemented to combat the hypoxia effect in the high altitude patients. We hypothesize that nitric oxide (NO) restores the peripheral blood mononuclear cell-matrix deadhesion during hypoxia. In the present study, we investigate the cellular action of exogenous NO in the hypoxia-mediated diminution of cell-matrix adhesion of PBMNC and NO bioavailability in vitro. The result showed that NO level and cell-matrix adhesion of PBMNC were significantly reduced in hypoxia as compared with normoxia, as assessed by the DAF-FM and cell adhesion assay, respectively. In contrast, cellular oxidative damage response was indeed upregulated in hypoxic PBMNC. Further, gene expression analysis revealed that mRNA transcripts of cell adhesion molecules (Integrin α5 and β1) and eNOS expressions were significantly downregulated. The mechanistic study revealed that administration of NO and 8-Br-cGMP and overexpression of eNOS-GFP restored the basal NO level and recovers cell-matrix adhesion in PBMNC via cGMP-dependent protein kinase I (PKG I) signalling. In conclusion, NO-cGMP/PKG signalling may constitute a novel target to recover high altitude-afflicted cellular deadhesion. SIGNIFICANCE OF THIS STUDY: Cellular adhesion is a complex multistep process. The ability of cells to adhere to extracellular matrix is an essential physiological process for normal homeostasis and function. Hypoxia exposure in the PBMNC culture has been proposed to induce oxidative damage and cellular deadhesion and is generally believed to be the key factor in the reduction of NO bioavailability. In the present study, we demonstrated that NO donor or overexpression of eNOS-GFP has a protective effect against hypoxia-induced cellular deadhesion and greatly improves the redox balance by inhibiting the oxidative stress. Furthermore, this protective effect of NO is mediated by the NO-cGMP/PKG signal pathway, which may provide a potential strategy against hypoxia.

Антиоксидантная система в реализации защитного действия оксида азота на растения пшеницы в условиях дефицита влаги

We studied the effect of a nitric oxide donor - SNP (sodium nitroprusside,) - on the growth and state of the components of the antioxidant system of wheat seedlings under conditions of dehydration modeled by 12% PEG. The protective effect of 200 µM SNP pretreatment on wheat plants was revealed, as evidenced by an increased content of reduced glutathione (GSH), a decrease in stress-induced accumulation of MDA, and glutathione S-transferase (GST) activity, which is reflected in maintaining a high level of growth processes. For the first time, the role of wheat germ agglutinin protein (WGA) in the manifestation of the protective effect of nitric oxide on wheat plants under stressful conditions is shown.

Protective effect of nitric oxide on QOL and mucosal injury induced by a constitutive administration of methotrexate to rats.

Protective effect of nitric oxide on QOL and mucosal injury induced by a constitutive administration of methotrexate to rats.

Does nitric oxide protect Eucalyptus urophylla seeds under salt stress conditions?

Abstract: The germination response of seeds under artificial stress conditions is a tool for better understanding of the survival and adaptation ability of species under natural stress conditions. The aims of this study were to evaluate the protective effect of nitric oxide during germination as well as seed vigor and seedling development of Eucalyptus urophylla under salt stress conditions. The experimental design was completely randomized, with five replications, in a 3 × 3 + 1 factorial arrangement, with three priming factors [water, sodium nitroprusside (SNP), and potassium nitrate (KNO3)], three germination conditions (distilled water, and the water potentials of -0.6 and -1.2 MPa), and an additional control treatment (unprimed seeds). The following determinations were made: germination count at seven and fourteen days, germination speed index, primary root length, shoot length, and total length. SNP protects seeds, leading to a higher percentage of germination, as well as greater root growth and total seedling size, whereas KNO3 is not effective in protecting seeds that suffer from salt stress, which affects their physiological and morphological characteristics. E. urophylla seeds are sensitive to salt stress, and physiological priming with SNP leads to an increase in the percentage of germination, vigor, and seedling development under salinity conditions.

CGMP-dependent protein kinase I in vascular smooth muscle cells improves ischemic stroke outcome in mice

Recent works highlight the therapeutic potential of targeting cyclic guanosine monophosphate (cGMP)-dependent pathways in the context of brain ischemia/reperfusion injury (IRI). Although cGMP-dependent protein kinase I (cGKI) has emerged as a key mediator of the protective effects of nitric oxide (NO) and cGMP, the mechanisms by which cGKI attenuates IRI remain poorly understood. We used a novel, conditional cGKI knockout mouse model to study its role in cerebral IRI. We assessed neurological deficit, infarct volume, and cerebral perfusion in tamoxifen-inducible vascular smooth muscle cell-specific cGKI knockout mice and control animals. Stroke experiments revealed greater cerebral infarct volume in smooth muscle cell specific cGKI knockout mice (males: 96 ± 16 mm3; females: 93 ± 12 mm3, mean±SD) than in all control groups: wild type (males: 66 ± 19; females: 64 ± 14), cGKI control (males: 65 ± 18; females: 62 ± 14), cGKI control with tamoxifen (males: 70 ± 8; females: 68 ± 10). Our results identify, for the first time, a protective role of cGKI in vascular smooth muscle cells during ischemic stroke injury. Moreover, this protective effect of cGKI was found to be independent of gender and was mediated via improved reperfusion. These results suggest that cGKI in vascular smooth muscle cells should be targeted by therapies designed to protect brain tissue against ischemic stroke.

Nitric oxide protected against NADPH oxidase-derived superoxide generation in vascular endothelium: Critical role for heme oxygenase-1

NADPH oxidase-derived superoxide (O2−) generation is usually considered as an important factor to the pathogenesis of cardiovascular diseases. Nitric oxide (NO), previously viewed as a key regulator of cardiovascular function, is identified to induce expression of heme oxygenase-1 (HO-1), an antioxidant enzyme in blood vessels. In this study, we tested whether NO might modulate NADPH oxidase activity in vascular endothelium via HO-1. In vascular endothelial cells, NO donor (diethylenetriamine/nitric oxide adduct) significantly attenuated NADPH oxidase-derived O2− generation via a HO-1-dependent mechanism. Mechanistically, the protective effects of NO were (1) linked to increased expression of HO-1, (2) similar to the effects of NADPH oxidase inhibitor, (3) could be abolished by the specific siRNA against HO-1 expression or HO-1 activity inhibitor and (4) similar to the effects of HO-1 end product bilirubin. Moreover, bilirubin seemed to interrupt the assembly and activation of NADPH oxidase. In addition, NO inhibited H2O2-induced endothelial dysfunction through activation of HO-1. In agreement with these in vitro data, aortic NADPH oxidase activity was increased in NO-deficient mice while the endothelial function was simultaneously impaired. Our results suggested that suppression of NADPH oxidase-dependent oxidative stress may represent a novel mechanism underlying the cardiovascular protection of NO/HO-1 pathway.

Protective Effects of Nitric Oxide and Phycocyanin Against Oxidative Stress Induced by Hepatic Ischemia/Reperfusion Injuries

Protective Effects of Nitric Oxide and Phycocyanin Against Oxidative Stress Induced by Hepatic Ischemia/Reperfusion Injuries

Nitric Oxide Generated by Tumor-Associated Macrophages Is Responsible for Cancer Resistance to Cisplatin and Correlated With Syntaxin 4 and Acid Sphingomyelinase Inhibition.

Tumor microenvironment is fundamental for cancer progression and chemoresistance. Among stromal cells tumor-associated macrophages (TAMs) represent the largest population of infiltrating inflammatory cells in malignant tumors, promoting their growth, invasion, and immune evasion. M2-polarized TAMs are endowed with the nitric oxide (NO)-generating enzyme inducible nitric oxide synthase (iNOS). NO has divergent effects on tumors, since it can either stimulate tumor cells growth or promote their death depending on the source of it; likewise the role of iNOS in cancer differs depending on the cell type. The role of NO generated by TAMs has not been investigated. Using different tumor models in vitro and in vivo we found that NO generated by iNOS of M2-polarized TAMs is able to protect tumor cells from apoptosis induced by the chemotherapeutic agent cisplatin (CDDP). Here, we demonstrate that the protective effect of NO depends on the inhibition of acid sphingomyelinase (A-SMase), which is activated by CDDP in a pathway involving the death receptor CD95. Mechanistic insights indicate that NO actions occur via generation of cyclic GMP and activation of protein kinase G (PKG), inducing phosphorylation of syntaxin 4 (synt4), a SNARE protein responsible for A-SMase trafficking and activation. Noteworthy, phosphorylation of synt4 at serine 78 by PKG is responsible for the proteasome-dependent degradation of synt4, which limits the CDDP-induced exposure of A-SMase to the plasma membrane of tumor cells. This inhibits the cytotoxic mechanism of CDDP reducing A-SMase-triggered apoptosis. This is the first demonstration that endogenous NO system is a key mechanism through which TAMs protect tumor cells from chemotherapeutic drug-induced apoptosis. The identification of the pathway responsible for A-SMase activity downregulation in tumors leading to chemoresistance warrants further investigations as a means to identify new anti-cancer molecules capable of specifically inhibiting synt4 degradation.

Protective Effects of Nitric Oxide on Photosynthetic Stability and Performance of Silybum marianum under Water Deficit Conditions

Core Ideas Milk thistle is a medicinal plant cultivating for production of silymarin and oil.The results our work showed that with the application of SNP photosynthesis, pigments content, and water status were improved in the drought stress condition and as a result significant increases in secondary metabolites production and grain yield was observed.Overall, this study suggest that application of 100 µM SNP and using Sari ecotype can be recommended for maximizing crop yield under drought stress in semiarid environment. Milk thistle is a medicinal plant cultivated for production of silymarin and oil. Nitric oxide as an active molecule, plays an important role in plant’s reaction to drought stress. In this study, we investigated the role of sodium nitroprusside (SNP) as a nitric oxide donor for tolerance enhancement of drought in two genotypes of milk thistle in a 2‐yr field experiment. With increasing drought severity, photosynthetic rate and stomatal conductance of milk thistle decreased significantly. The exogenous application of SNP significantly compensated for the negative effects of drought on photosynthetic rate by 40%, but also reduced stomatal conductance during 6 d after withholding irrigation. Drought stress significantly decreased pigments content and this affect was compensated by applying SNP in both genotypes. Among yield components, the number of heads per plant showed the highest sensitivity to drought stress followed by seed weight, while all yield components responded significantly to the application of SNP. Withholding irrigation significantly decreased seed yield in both genotypes and years. Averaged over 2 yr, application of 100 µM SNP in Sari ecotype at the stage of stem elongation and anthesis significantly improved seed yield by 38 and 33%, respectively, compared with the non‐application of SNP. However, in the Hungarian cultivar, SNP only led to a significant increase of 29% in seed yield during anthesis stress. Overall, this study suggest that application of SNP at a rate of 100 μM had potential to ameliorate the adverse effect of drought stress on photosynthetic rate and seed yield of milk thistle.

Cytokinins contribute to realization of nitric oxide growth-stimulating and protective effects on wheat plants

We investigated effects of sodium nitroprusside (SNP), the donor of nitric oxide (NO), on the growth and hormonal system of wheat plants (Triticum aestivum L.) in normal conditions and after salt stress (2% NaCl). During germination of seeds treated with SNP (50–500 μM), we obtained the SNP concentration (200 μM) optimal for stimulation of seedling growth estimated by increase in seed germination capacity and seedlings' linear sizes and their fresh and dry biomass. A comparative analysis of SNP (200 μM) effects, after seed germination in the medium with SNP or pretreatment of 3-day-old seedlings, showed SNP ability to increase the wheat plant resistance to subsequent effects of sodium chloride salinity at both treatment methods. Protective SNP effects appeared in the reduction of stress inhibitory action on seedling growth rates and significant reduction in the level of lipid peroxidation and exosmosis of electrolytes. An important contribution to realization of the growth-stimulating and protective effects of NO is associated with its ability to influence the state of the hormonal system of wheat plants due to an increase in the concentration of hormones of a cytokinin nature under normal conditions and the prevention of a decrease in their level under stress.

Low-Dose Sodium Nitrite Fluid Resuscitation Prevents Lethality From Crush Syndrome by Improving Nitric Oxide Consumption and Preventing Myoglobin Cytotoxicity in Kidney in A Rat Model.

Crush syndrome (CS) is a serious medical condition characterized by muscle cell damage resulting from pressure. CS has a high mortality, even when patients receive fluid therapy. We examined whether administration of NaNO2-containing fluid can improve survival in a rat model of CS. The CS model was generated by subjecting anesthetized rats to bilateral hind limb compression with a rubber tourniquet for 5 h. Rats were then randomly divided into six groups: sham; CS with no treatment; CS with normal saline treatment; CS with normal saline + 25 mEq/L bicarbonate treatment; and CS with normal saline + 200 or 500 μmol/kg NaNO2. Blood and tissue samples were collected for histological and biochemical analyses at predetermined time points before and after reperfusion. Ischemic compression of rat hind limbs reduced nitrite content in the crushed muscle, and subsequent reperfusion resulted in reactive oxygen species-induced circulatory dysfunction and systemic inflammation. Rats treated with 200 μmol/kg NaNO2 showed increased nitric oxide (NO) levels, blood circulation, and neoangiogenesis, decreased generation of reactive oxygen species, and suppression of the inflammatory response, leading to complete recovery. Treatment with 200 μmol/kg NaNO2 prevents muscle damage induced by ischemia reperfusion via the protective effects of NO and suppression of systemic inflammation, thereby increasing survival rates in CS.

Nitric oxide improves S-assimilation and GSH production to prevent inhibitory effects of cadmium stress on photosynthesis in mustard (Brassica juncea L.)

Nitric oxide (NO) is an important gaseous signalling molecule that participates in many developmental and physiological processes, including defense responses against toxic metals in plants. The role of NO in cadmium (Cd)-induced toxic effects on photosynthesis was examined in mustard (Brassica juncea L.) plants. Exposure of plants to 50 μM Cd significantly enhanced oxidative stress (H2O2 content and lipid peroxidation) and impaired plant growth and photosynthesis, chlorophyll fluorescence and reduced chlorophyll content and stomatal conductance. However, the exogenous application of 100 μM sodium nitroprusside (SNP, a donor of NO) reversed the effects of Cd through its stimulation of ROS-scavenging compounds (superoxide dismutase, ascorbate peroxidase, glutathione reductase and reduced glutathione). Exogenous SNP significantly increased plant growth, photosynthesis and chlorophyll content and diminished the accumulation of reactive oxygen species (H2O2) and TBARS content. It also reduced the effects of Cd on thylakoid membrane of the chloroplasts. Application of SNP together with 1.0 mM SO42- showed better responses than SNP alone. The protective effect of NO was achieved through enhanced production of reduced glutathione (GSH). GSH biosynthesis in plants treated with buthionine sulfoximine (BSO), a GSH biosynthetic inhibitor, was not completely inhibited in presence of NO and S, suggesting that NO stimulated S-assimilation and GSH production of Cd exposed plants. This study concludes that NO counteracts Cd toxicity in B. juncea strongly by regulating S-assimilation and GSH production.

Electrolyte Leakage and the Protective Effect of Nitric Oxide on Leaves of Flooded Rice Exposed to Herbicides

ABSTRACT The nitric oxide acts on the antioxidant system of plants and can discontinue the damage of herbicides elicitors of oxidative stress that cause the disruption of membranes and leakage of cellular contents. In order to evaluate the protective effect of nitric oxide in electrolytes leakage, leaf segments of the Puita INTA CL rice cultivar were incubated with 0, 5, 50, 500 and 5,000 μM clomazone (360 g a.i. L-1), oxadiazon (250 g a.i. L-1), oxyfluorfen (240 g a.i. L-1) and the formulated mixture of paraquat (200 g a.i. L-1) + diuron (100 g a.i. L-1) to obtain the maximum potential conductivity of 50% (MPC50). Subsequently, leaf segments were pre-treated with 0, 200 and 2,000 μM of sodium nitroprusside (SNP) for four hours and further incubated for 48 hours with 0, 0.5, 1, 2 and 4 times the concentration of the herbicide that caused the CMP50, and the protective effect was reassessed in the presence of nitric oxide scavenger, cPTIO. The MPC50 was caused by exposure to 188.9, 273.4, 410.2 + 205.1 and 917.0 μM of Oxadiazon, Oxyfluorfen, Paraquat + Diuron and Clomazone. Pretreatment with 200 μM of SNP reduced electrolyte leakage in leaf segments exposed to 2 and 4 times the MPC50 to oxadiazon and paraquat + diuron, while 2,000 μM reduced the damage caused by oxyfluorfen, at the same concentrations. Also, 200 and 2,000 μM of SNP were efficient for clomazone, and the protection was confirmed by cPTIO in all cases.

Protective Effect of Nitric Oxide (NO) against Oxidative Damage in Larix gmelinii Seedlings under Ultraviolet-B Irradiation

Ultraviolet-B (UV-B) stress appears to be more striking than other research works because of the thin ozone layer. The protective influence of an exogenous nitric oxide donor and sodium nitroprusside (SNP) on the growth properties of Larix gmelinii seedlings was investigated under ultraviolet-B radiation conditions. The results indicated that 0.1 mM SNP could effectively alleviate the damage caused by ultraviolet-B radiation, and improved the seedling growth properties, the relative water content, and photosynthetic pigment content in leaves. Additionally, the photosynthetic capacity and antioxidant enzyme activity were increased during the exposure. On the contrary, the damage caused by active oxygen was decreased in SNP-treated seedling leaves. The damage caused by ultraviolet-B radiation was slightly reduced after treating with 0.01 mM SNP. Nevertheless, treatment with 0.5 mM SNP had a negative effect under ultraviolet-B radiation. Furthermore, supplementing NO (nitric oxide) improved the photosynthetic capacity and antioxidant enzyme activity and alleviated the damage of caused by active oxygen. The best effective concentration of SNP was 0.1 mM. Therefore, a suitable amount of exogenous NO can protect the Larix gmelinii seedlings and increase their tolerance to ultraviolet-B radiation.

Cadmium stress tolerance in wheat seedlings induced by ascorbic acid was mediated by NO signaling pathways

Ascorbic acid (AsA) and nitric oxide (NO) are well known and widespread antioxidants and gaseous molecules that regulate plant tolerance to several stresses. However, the relationship between them in plant response to stress, especially heavy stress, is largely unclear. This study demonstrated that both AsA and NO could enhance the tolerance of wheat seedlings to cadmium stress evidenced by root length change, which resulted from their roles in maintaining the balance in reactive oxygen species (ROS) and reducing the absorption of Cd. Furthermore, exogenous AsA led to a significant increase of NO content and endogenous AsA content in wheat roots, which could be weakened by the NO scavenger c-PTIO. In addition, c-PTIO also inhibits the NO-induced production of endogenous AsA. Although the AsA synthesis inhibitor lycorine significantly inhibited the inductive effect of exogenous AsA on endogenous AsA production, it has little effect on NO content. In addition, we found that the protective effects of NO and AsA on Cd stress were removed by c-PTIO and lycorine. These results indicated that NO accumulation could be necessary for exogenous AsA-induced cadmium tolerance and endogenous AsA production, and the exogenous AsA-induced endogenous AsA production was likely mediated by NO signaling pathways and together they induced the tolerance of wheat to cadmium stress.

Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species.

There is increasing evidence that the permeability of the glomerular filtration barrier (GFB) is partly regulated by a balance between the bioavailability of nitric oxide (NO) and that of reactive oxygen species (ROS). It has been postulated that normal or moderately elevated NO levels protect the GFB from permeability increases, whereas ROS, through reducing the bioavailability of NO, have the opposite effect. We tested the tentative antagonism between NO and ROS on glomerular permeability in anaesthetized Wistar rats, in which the left ureter was cannulated for urine collection while simultaneously blood access was achieved. Rats were systemically infused with either l-NAME or l-NAME together with the superoxide scavenger Tempol, or together with l-arginine or the NO-donor DEA-NONOate, or the cGMP agonist 8-bromo-cGMP. To measure glomerular sieving coefficients (theta, θ) to Ficoll, rats were infused with FITC-Ficoll 70/400 (mol/radius 10-80 Å). Plasma and urine samples were analyzed by high-performance size-exclusion chromatography (HPSEC) for determination of θ for Ficoll repeatedly during up to 2 h. l-NAME increased θ for Ficoll70Å from 2.27 ± 1.30 × 10-5 to 8.46 ± 2.06 × 10-5 (n = 6, P < 0.001) in 15 min. Tempol abrogated these increases in glomerular permeability and an inhibition was also observed with l-arginine and with 8-bromo-cGMP. In conclusion, acute NO synthase inhibition in vivo by l-NAME caused rapid increases in glomerular permeability, which could be reversed by either an ROS antagonist or by activating the guanylyl cyclase-cGMP pathway. The data strongly suggest a protective effect of NO in maintaining normal glomerular permeability in vivo.

Protective effect of nitric oxide in aristolochic acid-induced toxic acute kidney injury: an old friend with new assets.

Aristolochic acid (AA) nephropathy (AAN), a progressive tubulointerstitial injury of toxic origin, is characterized by early and transient acute tubular necrosis. This process has been demonstrated to be associated with reduced nitric oxide (NO) production, which can disrupt the regulation of renal function. In this study, we tested the hypothesis that L-arginine (L-Arg) supplementation could restore renal function and reduce renal injury after AA intoxication. C57BL/6 J male mice were randomly subjected to daily i.p. injection of either sterile saline solution or AA (2.5 mg kg(-1)) for 4 days. To determine whether AA-induced renal injuries were linked to reduced NO production, L-Arg, a substrate for NO synthase, was supplemented (5%) in drinking water. Mice intoxicated with AA exhibited features of rapid-onset acute kidney injury, including polyuria, significantly increased plasma creatinine concentrations, proteinuria and fractional excretion of sodium (P < 0.05), along with severe proximal tubular cell injury and increased NADPH oxidase 2 (Nox2)-derived oxidative stress (P < 0.05). This was associated with a significant reduction in NO bioavailability. L-Arg supplementation in AA-treated mice significantly increased NO bioavailability, which in turn improved renal function (creatininaemia, polyuria, proteinuria, fractional excreted sodium and N-acetyl-β-D-glucosaminidase enzymuria) and renal structure (tubular necrosis and tubular cell apoptosis). These changes were associated with significant reductions in Nox2 expression and in production of reactive oxygen species and with an increase in antioxidant concentrations. Our results demonstrate that preservation of NO bioavailability leads to renal protection in AA-induced acute kidney injury by reducing oxidative stress and maintaining renal function.