scholarly journals N-acetylcysteine protects against diabetic nephropathy through control of oxidative and nitrosative stress by recovery of nitric oxide in rats

Nitric Oxide ◽  
2018 ◽  
Vol 78 ◽  
pp. 22-31 ◽  
Author(s):  
Guilherme B. Nogueira ◽  
Giovana R. Punaro ◽  
Clemerson S. Oliveira ◽  
Fabiane R. Maciel ◽  
Thamires O. Fernandes ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Diabetic Nephropathy ◽  
Nitrosative Stress ◽  
Oxidative And Nitrosative Stress

scholarly journals Protective effect of alpha lipoic acid on diabetic nephropathy in rats

2019 ◽  
Vol 20 (3) ◽  
pp. 19-23
Author(s):  
Samar Yabes ◽  
Mohamed EL-Adl ◽  
Mohamed Hamed ◽  
Gehad El-Sayed
Keyword(s):  
Diabetic Nephropathy ◽  
Lipoic Acid ◽  
Nitrosative Stress ◽  
Acid Group ◽  
Controlled Study ◽  
Alpha Lipoic Acid ◽  
Sprague Dawley ◽  
Glycemic Status ◽  
Oxidative And Nitrosative Stress ◽  
Tissue Samples

Objective: To evaluate the protective role of alpha lipoic acid in rats affected with experimentally-induced diabetes and secondarily complicated with nephropathy. Design: Randomized controlled study. Animals: Forty-eight Sprague Dawley rats. Procedures: Rats were allocated randomly into four groups (12 each); Control rats (Group 1); alpha lipoic acid (ALA) supplemented rats (Group 2); rats with induced diabetic nephropathy (Group 3), and rats with diabetic nephropathy and supplemented with alpha lipoic acid (Group 4). After one month of experimental induction, serum, plasma and renal tissue samples were harvested to determine glycemic status, renal damage markers, antioxidant status, oxidative and nitrosative stress markers, apoptotic marker and histopathology of kidney tissues. Results: In comparison with non-supplemented diabetic rats, alpha lipoic acid reduced renal malondialdehyde (5.74± 0.26 vs 11.3± 1.96 nmol/g. tissue) and renal nitric oxide (30.06± 2.07 vs 36.6± 1.07 nmol/g. tissue). ALA significantly improved the antioxidant enzyme activity (catalase and reduced glutathione), glycemic status, and decreased caspase 3 concentration (P<0.05). Conclusion and clinical relevance: Alpha lipoic acid may be an alternative intervention to alleviate nephropathy as a complication of diabetes. Further studies need to be done in naturally occurring cases.

scholarly journals Reduced oxidative and nitrosative damage in murine experimental colitis in the absence of inducible nitric oxide synthase

Gut ◽  
1999 ◽  
Vol 45 (2) ◽  
pp. 199-209 ◽  
Author(s):  
B Zingarelli ◽  
C Szabó ◽  
A L Salzman
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Experimental Colitis ◽  
Neutrophil Infiltration ◽  
Intercellular Adhesion Molecule ◽  
Myeloperoxidase Activity ◽  
Wild Type ◽  
Oxidative And Nitrosative Stress ◽  
Intense Staining ◽  
Genetic Ablation

BACKGROUNDOxidative and nitrosative stress have been implicated in the pathogenesis of inflammatory bowel diseases.AIMSTo study the role of nitric oxide (NO) derived from inducible NO synthase (iNOS) in an experimental model of murine enterocolitis.METHODSTrinitrobenzene sulphonic acid (TNBS) was instilled per rectum to induce a lethal colitis in iNOS deficient mice and in wild type controls. The distal colon was evaluated for histological evidence of inflammation, iNOS expression and activity, tyrosine nitration and malondialdehyde formation (as indexes of nitrosative and oxidative stress), myeloperoxidase activity (as index of neutrophil infiltration), and tissue localisation of intercellular adhesion molecule 1 (ICAM-1).RESULTSTNBS administration induced a high mortality and weight loss associated with a severe colonic mucosal erosion and ulceration, increased myeloperoxidase activity, increased concentrations of malondialdehyde, and an intense staining for nitrotyrosine and ICAM-1 in wild type mice. Genetic ablation of iNOS gene conferred to mice a significant resistance to TNBS induced lethality and colonic damage, and notably reduced nitrotyrosine formation and concentrations of malondialdehyde; it did not, however, affect neutrophil infiltration and intestinal ICAM-1 expression in the injured tissue.CONCLUSIONData show that activation of iNOS is required for nitrosative and oxidative damage in experimental colitis.

Renoprotective and antihypertensive effects of S-allylcysteine in 5/6 nephrectomized rats

2007 ◽  
Vol 293 (5) ◽  
pp. F1691-F1698 ◽  
Author(s):  
Cristino Cruz ◽  
Ricardo Correa-Rotter ◽  
Dolores Javier Sánchez-González ◽  
Rogelio Hernández-Pando ◽  
Perla D. Maldonado ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Inducible Nitric Oxide Synthase ◽  
Renal Damage ◽  
Nitrosative Stress ◽  
Antioxidant Properties ◽  
Oxidative And Nitrosative Stress ◽  
Nitric Oxide Synthase 3 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Progressive renal damage and hypertension are associated with oxidative and nitrosative stress. On the other hand, S-allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract (AG), has antioxidant properties. The effects of SAC and AG on blood pressure, renal damage, and oxidative and nitrosative stress were studied in five-sixths nephrectomized rats treated with SAC (200 mg/kg ip) and AG (1.2 ml/kg ip) every other day for 30 days. Proteinuria and serum creatinine and blood urea nitrogen concentrations were measured on days 0, 5, 10, 15, and 30, and systolic blood pressure was recorded on days 0, 15, and 30. The degree of glomerulosclerosis and tubulointerstitial damage, the immunostaining for inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), and the subunits of NADPH oxidase p22phox and gp91phox, and the activity of SOD were determined on day 30. SAC and AG reduced hypertension, renal damage, and the abundance of inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), p22phox, and gp91phox and increased SOD activity. Our data suggest that the antihypertensive and renoprotective effects of SAC and AG are associated with their antioxidant properties and that they may be used to ameliorate hypertension and delay the progression of renal damage.

scholarly journals Roles of Nitric Oxide and Prostaglandins in the Sustained Antihypertensive Effects of Acanthospermum hispidum DC. on Ovariectomized Rats with Renovascular Hypertension

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Rhanany Alan Calloi Palozi ◽  
Maysa Isernhagen Schaedler ◽  
Cleide Adriane Signor Tirloni ◽  
Aniely Oliveira Silva ◽  
Francislaine Aparecida dos Reis Lívero ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renovascular Hypertension ◽  
Vascular Reactivity ◽  
Nitrosative Stress ◽  
Folk Medicine ◽  
Thiobarbituric Acid ◽  
Ovariectomized Rats ◽  
Oxidative And Nitrosative Stress ◽  
Antihypertensive Response

Although Acanthospermum hispidum is used in Brazilian folk medicine as an antihypertensive, no study evaluated its effects on a renovascular hypertension and ovariectomy model. So, this study investigated the mechanisms involved in the antihypertensive effects of an ethanol-soluble fraction obtained from A. hispidum (ESAH) using two-kidney-one-clip hypertension in ovariectomized rats (2K1C plus OVT). ESAH was orally administered at doses of 30, 100, and 300 mg/kg, daily, for 28 days, after 5 weeks of surgery. Enalapril (15 mg/kg) and hydrochlorothiazide (25 mg/kg) were used as standard drugs. Diuretic activity was evaluated on days 1, 7, 14, 21, and 28. Systolic, diastolic, and mean blood pressure and heart rate were recorded. Serum creatinine, urea, thiobarbituric acid reactive substances, nitrosamine, nitrite, aldosterone, vasopressin levels, and ACE activity were measured. The vascular reactivity and the role of nitric oxide (NO) and prostaglandins (PG) in the vasodilator response of ESAH on the mesenteric vascular bed (MVB) were also investigated. ESAH treatment induced an important saluretic and antihypertensive response, therefore recovering vascular reactivity in 2K1C plus OVT-rats. This effect was associated with a reduction of oxidative and nitrosative stress with a possible increase in the NO bioavailability. Additionally, a NO and PG-dependent vasodilator effect was observed on the MEV.

Oxidative and nitrosative stress in acute renal ischemia

2001 ◽  
Vol 281 (5) ◽  
pp. F948-F957 ◽  
Author(s):  
Eisei Noiri ◽  
Akihide Nakao ◽  
Koji Uchida ◽  
Hirokazu Tsukahara ◽  
Minoru Ohno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lipid Peroxidation ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Nitrosative Stress ◽  
Oxidative And Nitrosative Stress ◽  
Reperfusion Period ◽  
Series Of Experiments ◽  
Acute Renal Ischemia ◽  
Oxide Synthase

First Published July 12, 2001; 10.1152/ajprenal.0071.2001.—Generation of reactive oxygen species and nitric oxide in hypoxia-reperfusion injury may form a cytotoxic metabolite, peroxynitrite, which is capable of causing lipid peroxidation and DNA damage. This study was designed to examine the contribution of oxidative and nitrosative stress to the renal damage in ischemic acute renal failure (iARF). iARF was initiated in rats by 45-min renal artery clamping. This resulted in lipid peroxidation, DNA damage, and nitrotyrosine modification confirmed both by Western and immunohistochemical analyses. Three groups of animals were randomly treated with an inhibitor of inducible nitric oxide synthase (NOS),l- N 6-(1-iminoethyl)lysine (l-Nil), cell-permeable lecithinized superoxide dismutase (SOD), or both. Each treatment resulted in amelioration of renal dysfunction, as well as reduced nitrotyrosine formation, lipid peroxidation, and DNA damage, thus suggesting that peroxynitrite rather than superoxide anion is responsible for lipid peroxidation and DNA damage. Therefore, in a separate series of experiments, a scavenger of peroxynitrite, ebselen, was administered before the reperfusion period. This treatment resulted in a comparable degree of amelioration of iARF. In conclusion, the present study provides the first attempt to elucidate the role of peroxynitrite in initiation of the cascade of lipid peroxidation and DNA damage to ischemic kidneys. The results demonstrate that l-Nil , lecithinized SOD, and ebselen treatments improve renal function due to their suppression of peroxynitrite production or its scavenging, consequently preventing lipid peroxidation and oxidative DNA damage.

scholarly journals Leaky brain in neurological and psychiatric disorders: Drivers and consequences

2018 ◽  
Vol 52 (10) ◽  
pp. 924-948 ◽  
Author(s):  
Gerwyn Morris ◽  
Brisa S Fernandes ◽  
Basant K Puri ◽  
Adam J Walker ◽  
Andre F Carvalho ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Brain Barrier ◽  
Inflammatory Cytokines ◽  
Nitrosative Stress ◽  
Brain Barrier ◽  
Leaky Gut ◽  
Oxidative And Nitrosative Stress ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Pro Inflammatory Cytokines

Background: The blood–brain barrier acts as a highly regulated interface; its dysfunction may exacerbate, and perhaps initiate, neurological and neuropsychiatric disorders. Methods: In this narrative review, focussing on redox, inflammatory and mitochondrial pathways and their effects on the blood–brain barrier, a model is proposed detailing mechanisms which might explain how increases in blood–brain barrier permeability occur and can be maintained with increasing inflammatory and oxidative and nitrosative stress being the initial drivers. Results: Peripheral inflammation, which is causatively implicated in the pathogenesis of major psychiatric disorders, is associated with elevated peripheral pro-inflammatory cytokines, which in turn cause increased blood–brain barrier permeability. Reactive oxygen species, such as superoxide radicals and hydrogen peroxide, and reactive nitrogen species, such as nitric oxide and peroxynitrite, play essential roles in normal brain capillary endothelial cell functioning; however, chronically elevated oxidative and nitrosative stress can lead to mitochondrial dysfunction and damage to the blood–brain barrier. Activated microglia, redox control of which is mediated by nitric oxide synthases and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, secrete neurotoxic molecules such as reactive oxygen species, nitric oxide, prostaglandin, cyclooxygenase-2, quinolinic acid, several chemokines (including monocyte chemoattractant protein-1 [MCP-1], C-X-C motif chemokine ligand 1 [CXCL-1] and macrophage inflammatory protein 1α [MIP-1α]) and the pro-inflammatory cytokines interleukin-6, tumour necrosis factor-α and interleukin-1β, which can exert a detrimental effect on blood–brain barrier integrity and function. Similarly, reactive astrocytes produce neurotoxic molecules such as prostaglandin E2 and pro-inflammatory cytokines, which can cause a ‘leaky brain’. Conclusion: Chronic inflammatory and oxidative and nitrosative stress is associated with the development of a ‘leaky gut’. The following evidence-based approaches, which address the leaky gut and blood–brain barrier dysfunction, are suggested as potential therapeutic interventions for neurological and neuropsychiatric disorders: melatonin, statins, probiotics containing Bifidobacteria and Lactobacilli, N-acetylcysteine, and prebiotics containing fructo-oligosaccharides and galacto-oligosaccharides.

Sex differences in nitrosative stress during renal ischemia

2010 ◽  
Vol 299 (5) ◽  
pp. R1387-R1395 ◽  
Author(s):  
Francisca Rodríguez ◽  
Susana Nieto-Cerón ◽  
Francisco J. Fenoy ◽  
Bernardo López ◽  
Isabel Hernández ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sex Differences ◽  
Nitric Oxide Synthase ◽  
Nitrosative Stress ◽  
Differential Pulse ◽  
Sprague Dawley ◽  
Oxidative And Nitrosative Stress ◽  
Sprague Dawley Rats ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Females. suffer a less severe ischemic acute renal failure than males, apparently because of higher nitric oxide (NO) bioavailability and/or lower levels of oxidative stress. Because the renal ischemic injury is associated with outer medullary (OM) endothelial dysfunction, the present study evaluated sex differences in OM changes of NO and peroxynitrite levels (by differential pulse voltammetry and amperometry, respectively) during 45 min of ischemia and 60 min of reperfusion in anesthetized Sprague-Dawley rats. Endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) protein expression and their phosphorylated forms [peNOS(Ser1177) and pnNOS(Ser1417)], 3-nitrotyrosine, reduced sulfhydryl groups (-SH), and glomerular filtration rate (GFR) were also determined. No sex differences were observed in monomeric eNOS and nNOS expression, NO, or 3-nitrotyrosine levels in nonischemic kidneys, but renal -SH content was higher in females. Ischemia increased dimeric/monomeric eNOS and nNOS ratio more in females, but the dimeric phosphorylated peNOS(Ser1177) and pnNOS(Ser1417) forms rose similarly in both sexes, indicating no sex differences in nitric oxide synthase activation. However, NO levels increased more in females than in males (6,406.0 ± 742.5 and 4,058.2 ± 272.35 nmol/l respectively, P < 0.05), together with a lower increase in peroxynitrite current (5.5 ± 0.7 vs. 12.7 ± 1.5 nA, P < 0.05) and 3-nitrotyrosine concentration, (28.7 ± 3.7 vs. 48.7 ± 3.7 nmol/mg protein, P < 0.05) in females than in males and a better preserved GFR after ischemia in females than in males (689.7 ± 135.0 and 221.4 ± 52.5 μl·min−1·g kidney wt−1, P < 0.01). Pretreatment with the antioxidants N-acetyl-l-cysteine or ebselen abolished sex differences in peroxynitrite, nitrotyrosine, and GFR, suggesting that a greater oxidative and nitrosative stress worsens renal damage in males.

scholarly journals Oxidative and nitrosative stress in brain mitochondria of diabetic rats

2005 ◽  
Vol 187 (1) ◽  
pp. 37-44 ◽  
Author(s):  
R Mastrocola ◽  
F Restivo ◽  
I Vercellinatto ◽  
O Danni ◽  
E Brignardello ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Manganese Superoxide Dismutase ◽  
Nitrosative Stress ◽  
Neuronal Damage ◽  
Brain Mitochondria ◽  
Brain Dysfunction ◽  
Diabetic Rats ◽  
Oxidative And Nitrosative Stress ◽  
Chronic Hyperglycemia ◽  
Mitochondrial Nitric Oxide Synthase

Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, may involve direct neuronal damage caused by intracellular glucose. The study assesses the direct effect of chronic hyperglycemia on the function of brain mitochondria, the major site of reactive species production, in diabetic streptozotocin (STZ) rats. Oxidative stress plays a central role in diabetic tissue damage. Alongside enhanced reactive oxygen species (ROS) levels, both nitric oxide (NO) levels and mitochondrial nitric oxide synthase expression were found to be increased in mitochondria, whereas glutathione (GSH) peroxidase activity and manganese superoxide dismutase protein content were reduced. GSH was reduced and GSH disulfide (GSSG) was increased in STZ rats. Oxidative and nitrosative stress, by reducing the activity of complexes III, IV and V of the respiratory chain and decreasing ATP levels, might contribute to mitochondrial dysfunction. In summary, this study offers fresh evidence that, besides the vascular-dependent mechanisms of brain dysfunction, oxidative and nitrosative stress, by damaging brain mitochondria, may cause direct injury of neuronal cells.

scholarly journals Distinct Stress Responses of Two Functional Laccases in Cryptococcus neoformans Are Revealed in the Absence of the Thiol-Specific Antioxidant Tsa1

2005 ◽  
Vol 4 (1) ◽  
pp. 202-208 ◽  
Author(s):  
Tricia A. Missall ◽  
Jason M. Moran ◽  
John A. Corbett ◽  
Jennifer K. Lodge
Keyword(s):  
Nitric Oxide ◽  
Cryptococcus Neoformans ◽  
Stress Responses ◽  
Fungal Pathogens ◽  
Nitrosative Stress ◽  
Fluorescent Protein ◽  
Resistance Mechanisms ◽  
Radical Scavenger ◽  
Homologous Gene ◽  
Oxidative And Nitrosative Stress

ABSTRACT Laccases are thought to be important to the virulence of many fungal pathogens by producing melanin, a presumed oxygen radical scavenger. A laccase in Cryptococcus neoformans has been shown to synthesize melanin and contributes to the virulence and the survival in macrophages of this fungal pathogen. One C. neoformans laccase gene, LAC1, previously called CNLAC1, has been extensively studied, and we describe a homologous gene, LAC2, that is found 8 kb away from LAC1 in the genome. In this study we report a role for both laccases, in addition to the thiol peroxidase, Tsa1, in oxidative and nitrosative stress resistance mechanisms of C. neoformans. With use of real-time PCR, similar changes in expression of the two laccase genes occur in response to oxidative and nitrosative stresses, but only the regulation of the LAC2 gene during stress is influenced by Tsa1. Both laccases contribute to melanin production using L-dopa as a substrate and are differentially localized in the cell based on green fluorescent protein fusions. A single deletion of either LAC1 or LAC2 alone had no effect on sensitivity to H2O2 or nitric oxide. However, deletion of either LAC1 or LAC2 in combination with a TSA1 deletion resulted in a slight peroxide sensitivity, and a lac2Δ tsa1Δ deletion strain was sensitive to nitric oxide stress. In addition, the deletion of both laccases reduces survival of C. neoformans in primary macrophages. Based on our expression and functional analysis, we propose a novel model for the interaction of these two systems, which are both important for virulence.

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