scholarly journals Curcumin Modulates Nitrosative Stress, Inflammation and DNA Damage and Protects against Ochratoxin A-Induced Hepatotoxicity and Nephrotoxicity in Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1239
Author(s):  
Consiglia Longobardi ◽  
Sara Damiano ◽  
Emanuela Andretta ◽  
Francesco Prisco ◽  
Valeria Russo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dna Damage ◽  
Ochratoxin A ◽  
Oxidative Dna Damage ◽  
Nitrosative Stress ◽  
Antioxidant Activities ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Natural Polyphenol ◽  
Oxide Synthase

Ochratoxin A (OTA) is a fungal toxin of critical concern for food safety both for human health and several animal species, also representing a cancer threat to humans. Curcumin (CURC) is a natural polyphenol that has anti-apoptotic, anti-inflammatory, and antioxidant effects. The aim of this study was to investigate the cytoprotective effect of CURC against OTA-induced nephrotoxicity and hepatotoxicity through the study of the nitrosative stress, pro-inflammatory cytokines, and deoxyribonucleic acid (DNA) damage. Sprague Dawley rats were daily treated with CURC (100 mg/kg b.w.), OTA (0.5 mg/kg b.w), or CURC with OTA by oral gavage for 14 days. Our results demonstrated that OTA exposure was associated with significant increase of pro-inflammatory and DNA oxidative-damage biomarkers. Moreover, OTA induced the inducible nitric oxide synthase, (iNOS) resulting in increased nitric oxide (NO) levels both in kidney and liver. The co-treatment OTA + CURC counteracted the harmful effects of chronic OTA treatment by regulating inflammation, reducing NO levels and oxidative DNA damage in kidney and liver tissues. Histology revealed that OTA + CURC treatment determinates mainly an Iba1+ macrophagic infiltration with fewer CD3+ T-lymphocytes in the tissues. In conclusion, we evidenced that CURC exerted cytoprotective and antioxidant activities against OTA-induced toxicity in rats.

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.

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.

Differential sympathetic nerve responses to nitric oxide synthase inhibition in anesthetized rats

1995 ◽  
Vol 269 (4) ◽  
pp. R807-R813 ◽  
Author(s):  
T. Hirai ◽  
T. I. Musch ◽  
D. A. Morgan ◽  
K. C. Kregel ◽  
D. E. Claassen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sympathetic Nerve ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Important Means ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Tonic Excitation

Recent studies have suggested that the interaction between the sympathetic nervous system and nitric oxide (NO) or nitrosyl factors may be an important means by which arterial blood pressure is regulated. We investigated whether NO synthase (NOS) inhibition modulates basal sympathetic nerve discharge (SND) in baroreceptor-innervated and -denervated, chloralose-anesthetized Sprague-Dawley rats. We recorded mean arterial pressure (MAP), renal SND, and lumbar SND before and after administration of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg iv). Two minutes after L-NAME administration in baroreceptor-innervated rats, MAP increased (+23 +/- 3 mmHg), whereas renal (-45 +/- 6%, n = 7) and lumbar (-35 +/- 2%, n = 6) SND significantly decreased from control levels. These changes persisted for up to 20 min after L-NAME administration. In baroreceptor-denervated rats, L-NAME increased MAP (+40 +/- 6 mmHg) and decreased lumbar SND (n = 7) (-37 +/- 10% from control at 20 min post-L-NAME). In contrast, renal SND progressively increased (+33 +/- 8% at 20 min post-L-NAME) from control after L-NAME administration in baroreceptor-denervated rats (n = 7). These results demonstrate that NOS inhibition can produce nonuniform changes in SND in baroreceptor-denervated rats and suggest that endogenous nitrosyl factors provide tonic excitation to lumbar SND, whereas they provide a tonic restraint to renal SND.

scholarly journals Hypertensive female Sprague-Dawley rats require an intact nitric oxide synthase system for compensatory increases in renal regulatory T cells

2020 ◽  
Vol 319 (2) ◽  
pp. F192-F201
Author(s):  
Lindsey A. Ramirez ◽  
Ellen E. Gillis ◽  
Jacqueline B. Musall ◽  
Riyaz Mohamed ◽  
Elizabeth Snyder ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Regulatory T Cells ◽  
Female Rats ◽  
Sprague Dawley ◽  
Albumin Excretion ◽  
Sprague Dawley Rats ◽  
Oxide Synthase

We have previously shown that hypertensive female rats have more regulatory T cells (Tregs), which contribute more to blood pressure (BP) control in female versus male rats. Based on known protective properties of Tregs, the goal of the present study was to investigate the mechanisms by which female rats maintain Tregs. The present study was designed to 1) compare the impact of three hypertension models on the percentage of renal Tregs and 2) test the hypothesis that nitric oxide synthase (NOS) inhibition prevents increases in renal Tregs and exacerbates renal damage in female Sprague-Dawley rats. Rats (11–14 wk old) were randomized to one of the following four groups: control, norepinephrine (NE) infusion, angiotensin II infusion, or the NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) in drinking water. BP was measured via tail cuff. After 2 wk of treatment, kidneys were isolated and processed to measure Tregs via flow cytometric analysis and renal injury via urinary albumin excretion, plasma creatinine, and histological analyses. Hypertensive treatments increased BP in all experimental animals. Increases in BP in norepinephrine-and angiotensin II-treated rats were associated with increases in renal Tregs versus control. In contrast, l-NAME treatment decreased Tregs compared with all groups. l-NAME treatment modestly increased albumin excretion. However, plasma creatinine was comparable among the groups, and there was no histological evidence of glomerular or tubular injury. This study provides insights into the mechanisms regulating renal Tregs and supports that an intact NOS system is crucial for female rats to have BP-related increases in renal Tregs.

Nitric oxide modulation of glutamatergic, baroreflex, and cardiopulmonary transmission in the nucleus of the solitary tract

2005 ◽  
Vol 288 (1) ◽  
pp. H256-H262 ◽  
Author(s):  
Ana Carolina Rodrigues Dias ◽  
Melissa Vitela ◽  
Eduardo Colombari ◽  
Steven W. Mifflin
Keyword(s):  
Nitric Oxide ◽  
Solitary Tract ◽  
Glutamatergic Transmission ◽  
Sprague Dawley ◽  
Renal Sympathetic Nerve Activity ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Nos Inhibitor ◽  
The Right ◽  
Oxide Synthase

The neuromodulatory effect of NO on glutamatergic transmission has been studied in several brain areas. Our previous single-cell studies suggested that NO facilitates glutamatergic transmission in the nucleus of the solitary tract (NTS). In this study, we examined the effect of the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME) on glutamatergic and reflex transmission in the NTS. We measured mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) from Inactin-anesthetized Sprague-Dawley rats. Bilateral microinjections of l-NAME (10 nmol/100 nl) into the NTS did not cause significant changes in basal MAP, HR, or RSNA. Unilateral microinjection of ( RS)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 1 pmol/100 nl) into the NTS decreased MAP and RSNA. Fifteen minutes after l-NAME microinjections, AMPA-evoked cardiovascular changes were significantly reduced. N-methyl-d-aspartate (NMDA, 0.5 pmol/100 nl) microinjection into the NTS decreased MAP, HR, and RSNA. NMDA-evoked falls in MAP, HR, and RSNA were significantly reduced 30 min after l-NAME. To examine baroreceptor and cardiopulmonary reflex function, l-NAME was microinjected at multiple sites within the rostro-caudal extent of the NTS. Baroreflex function was tested with phenylephrine (PE, 25 μg iv) before and after l-NAME. Five minutes after l-NAME the decrease in RSNA caused by PE was significantly reduced. To examine cardiopulmonary reflex function, phenylbiguanide (PBG, 8 μg/kg) was injected into the right atrium. PBG-evoked hypotension, bradycardia, and RSNA reduction were significantly attenuated 5 min after l-NAME. Our results indicate that inhibition of NOS within the NTS attenuates baro- and cardiopulmonary reflexes, suggesting that NO plays a physiologically significant neuromodulatory role in cardiovascular regulation.

scholarly journals Acrylonitrile-Induced Oxidative Stress and Oxidative DNA Damage in Male Sprague-Dawley Rats

2009 ◽  
Vol 111 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Xinzhu Pu ◽  
Lisa M. Kamendulis ◽  
James E. Klaunig
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

Distensibility and wall composition of rat cerebral arterioles in hypertension induced by chronic blockade of nitric oxide synthase

1996 ◽  
Vol 54 ◽  
pp. 754-755
Author(s):  
S. M. Ghoneim ◽  
J. M. Chillon ◽  
G.L. Baumbach
Keyword(s):  
Nitric Oxide ◽  
Vessel Wall ◽  
Mass Composition ◽  
Chronic Hypertension ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Sprague Dawley Rats ◽  
Cacodylate Buffer ◽  
Cerebral Arterioles ◽  
Oxide Synthase

We have previously reported that, during chronic hypertension, cerebral arterioles undergo hypertrophy of the vessel wall, accompanied by a paradoxical increase in passive distensibility. We have proposed that this increase may be due to a reduction in the proportion of nondistensible (collagen and basement membrane) to the distensible (smooth muscle, elastin and endothelium) components of the vessel wall. We have recently observed in stroke-prone spontaneously hypertensive rats(SHRSP), that an endothelium derived factor, endothelin, may contribute to hypertrophy, but not to increases in passive ditensibility, of cerebral arterioles vessel wall.The goal of this study was to examine wall mass, composition and passive ditensibility of cerebral arterioles in chronic hypertension induced by decreased availability of another endothelium derived factor, nitric oxide (NO).Four weeks old male Sprague-Dawley rats were treated with LG-nitro-L-arginine methyl ester (LNAME; 10 mg /kg/day) in the drinking water. We examined distensibility of maximally dilated cerebral arterioles in 4 months old Sprague-Dawley rats. Arterioles were then fixed at physiological pressure (2.25% gluterladehyde in 0.10 mol/L cacodylate buffer), the arteriolar segment used for distensibility measurements was removed then immerse fixed, rinsed briefly in 0.1 M cacodylate buffer, osmicated and processed routinely for electron microscopy (TEM).

scholarly journals Augmented central nitric oxide production inhibits vasopressin release during hemorrhage in acute alcohol-intoxicated rodents

2011 ◽  
Vol 301 (5) ◽  
pp. R1529-R1539 ◽  
Author(s):  
Annie M. Whitaker ◽  
Jesse K. Sulzer ◽  
Patricia E. Molina
Keyword(s):  
Nitric Oxide ◽  
Alcohol Intoxication ◽  
Sprague Dawley ◽  
Nitric Oxide Synthase Inhibitor ◽  
Vasopressin Release ◽  
No Inhibition ◽  
Sprague Dawley Rats ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Acute alcohol intoxication (AAI) attenuates the AVP response to hemorrhage, contributing to impaired hemodynamic counter-regulation. This can be restored by central cholinergic stimulation, implicating disrupted signaling regulating AVP release. AVP is released in response to hemorrhage and hyperosmolality. Studies have demonstrated nitric oxide (NO) to play an inhibitory role on AVP release. AAI has been shown to increase NO content in the paraventricular nucleus. We hypothesized that the attenuated AVP response to hemorrhage during AAI is the result of increased central NO inhibition. In addition, we predicted that the increased NO tone during AAI would impair the AVP response to hyperosmolality. Conscious male Sprague-Dawley rats (300–325 g) received a 15-h intragastric infusion of alcohol (2.5 g/kg + 300 mg·kg−1·h−1) or dextrose prior to a 60-min fixed-pressure hemorrhage (∼40 mmHg) or 5% hypertonic saline infusion (0.05 ml·kg−1·min−1). AAI attenuated the AVP response to hemorrhage, which was associated with increased paraventricular NO content. In contrast, AAI did not impair the AVP response to hyperosmolality. This was accompanied by decreased paraventricular NO content. To confirm the role of NO in the alcohol-induced inhibition of AVP release during hemorrhage, the nitric oxide synthase inhibitor, nitro-l-arginine methyl ester (l-NAME; 250 μg/5 μl), was administered centrally prior to hemorrhage. l-NAME did not further increase AVP levels during hemorrhage in dextrose-treated animals; however, it restored the AVP response during AAI. These results indicate that AAI impairs the AVP response to hemorrhage, while not affecting the response to hyperosmolality. Furthermore, these data demonstrate that the attenuated AVP response to hemorrhage is the result of augmented central NO inhibition.

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