VITAMIN C REDUCES DOXORUBICIN-INDUCED NITROSATIVE STRESS BY REGULATION OF NITRIC OXIDE SYNTHASE

2015 ◽  
Vol 31 (10) ◽  
pp. S66 ◽  
Author(s):  
G. Akolkar ◽  
A. Bagchi ◽  
D. Jassal ◽  
P. Singal
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Vitamin C ◽  
Nitrosative Stress ◽  
Oxide Synthase

scholarly journals Doxorubicin-induced nitrosative stress is mitigated by vitamin C via the modulation of nitric oxide synthases

2017 ◽  
Vol 312 (4) ◽  
pp. C418-C427 ◽  
Author(s):  
Gauri Akolkar ◽  
Ashim K. Bagchi ◽  
Prathapan Ayyappan ◽  
Davinder S. Jassal ◽  
Pawan K. Singal
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Vitamin C ◽  
Protein Expression ◽  
Nitrosative Stress ◽  
Sprague Dawley ◽  
The Stability ◽  
Oxide Synthase ◽  
Nos Isoforms ◽  
Vit C

An increase in oxidative stress is suggested to be the main cause in Doxorubicin (Dox)–induced cardiotoxicity. However, there is now evidence that activation of inducible nitric oxide synthase (iNOS) and nitrosative stress are also involved. The role of vitamin C (Vit C) in the regulation of nitric oxide synthase (NOS) and reduction of nitrosative stress in Dox-induced cardiotoxicity is unknown. The present study investigated the effects of Vit C in the mitigation of Dox-induced changes in the levels of nitric oxide (NO), NOS activity, protein expression of NOS isoforms, and nitrosative stress as well as cytokines TNF-α and IL-10 in isolated cardiomyocytes. Cardiomyocytes isolated from adult Sprague-Dawley rats were segregated into four groups: 1) control, 2) Vit C (25 µM), 3) Dox (10 µM), and 4) Vit C + Dox. Dox caused a significant increase in the generation of superoxide radical (O2·−), peroxynitrite, and NO, and these effects of Dox were blunted by Vit C. Dox increased the expression of iNOS and altered protein expression as well as activation of endothelial NOS (eNOS). These changes were prevented by Vit C. Dox induced an increase in the ratio of monomeric/dimeric eNOS, promoting the production of O2·−, which was prevented by Vit C by increasing the stability of the dimeric form of eNOS. Vit C protected against the Dox-induced increase in TNFα as well as a reduction in IL-10. These results suggest that Vit C provides cardioprotection by reducing oxidative/nitrosative stress and inflammation via a modulation of Dox-induced increase in the NO levels and NOS activity.

Stimulation of the endogenous hydrogen sulfide synthesis suppresses oxidative–nitrosative stress and restores endothelial-dependent vasorelaxation in old rats

2020 ◽  
Vol 98 (5) ◽  
pp. 275-281 ◽  
Author(s):  
L.A. Mys ◽  
N.A. Strutynska ◽  
Y.V. Goshovska ◽  
V.F. Sagach
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Nitric Oxide Synthase ◽  
Vascular Reactivity ◽  
Nitrosative Stress ◽  
Rat Aorta ◽  
Aortic Tissue ◽  
Old Rats ◽  
Oxide Synthase ◽  
Stimulation Of

Hydrogen sulfide (H2S) is an endogenous gas transmitter with profound effects on the cardiovascular system. We hypothesized that stimulation of H2S synthesis might alleviate age-associated changes in vascular reactivity. Pyridoxal-5-phosphate (PLP), the coenzyme of H2S-synthesizing enzymes, was administrated to old male Wistar rats per os at a dose of 0.7 mg/kg body mass once a day for 2 weeks. H2S content in the aortic tissue, markers of oxidative stress, inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS), arginase activities, and endothelium-dependent vasorelaxation of the aortic rings were studied. Our results showed that PLP restored endogenous H2S and low molecular weight S-nitrosothiol levels in old rat aorta to the levels detected in adults. PLP significantly reduced diene conjugate content, hydrogen peroxide and peroxynitrite generation rates, and iNOS and arginase activity in the aortic tissue of old rats. PLP also greatly improved acetylcholine-induced relaxation of old rat aorta (47.7% ± 4.8% versus 18.4% ± 4.1% in old rats, P < 0.05) that was abolished by NO inhibition with N-nitro-l-arginine methyl ester hydrochloride (L-NAME) or H2S inhibition with O-carboxymethylhydroxylamine (O-CMH). Thus, PLP might be used for stimulation of endogenous H2S synthesis and correction of oxidative and nitrosative stress and vessel tone dysfunction in aging and age-associated diseases.

Nitric oxide synthase and oxidative-nitrosative stress play a key role in placental infection byTrypanosoma cruzi

2018 ◽  
Vol 80 (1) ◽  
pp. e12852 ◽  
Author(s):  
María Fernanda Triquell ◽  
Cintia Díaz-Luján ◽  
María Cristina Romanini ◽  
Juan Carlos Ramirez ◽  
Patricia Paglini-Oliva ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nitrosative Stress ◽  
Placental Infection ◽  
Oxide Synthase

scholarly journals Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Iva Bozic ◽  
Danijela Savic ◽  
Marija Jovanovic ◽  
Ivana Bjelobaba ◽  
Danijela Laketa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Low Dose ◽  
Nitrosative Stress ◽  
Morphological Changes ◽  
Necrosis Factor Alpha ◽  
External Threats ◽  
Cytokine Tumor Necrosis Factor ◽  
Induced Apoptosis ◽  
Oxide Synthase

Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM) modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM) to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS) stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation.

Transiently, paralleled upregulation of arginase and nitric oxide synthase and the effect of both enzymes on the pathology of asthma

2007 ◽  
Vol 293 (6) ◽  
pp. L1419-L1426 ◽  
Author(s):  
Kei Takemoto ◽  
Keiki Ogino ◽  
Masafumi Shibamori ◽  
Toshikazu Gondo ◽  
Yoshiaki Hitomi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Mrna Expression ◽  
Nitrosative Stress ◽  
Dermatophagoides Farinae ◽  
Cell Hyperplasia ◽  
Bronchial Epithelial ◽  
Nitrite Nitrate ◽  
Oxide Synthase ◽  
Arginase I

Changes in the expression of arginase and their association with nitrosative stress were investigated using an asthmatic model previously established in NC/Nga mice with mite extract. Mite crude extract (100 μg/day) from Dermatophagoides farinae was administered intranasally for 5 consecutive days ( day 0–4), and a single challenge was performed on day 11. On day 12, upregulation of the mRNA expression of inducible types of nitric oxide synthase (iNOS) and increases in immunohistochemical staining for iNOS and nitrotyrosine were observed. However, the level of nitrite + nitrate was unchanged. An increase in enzymatic activity, upregulation of mRNA expression, and immunostaining for arginase I was detected in the lung tissue and serum. Moreover, increases in both arginase I and II were revealed by immunoblotting. Goblet cell hyperplasia in bronchial epithelial cells and increasing collagen synthesis around the bronchus were also observed. These results suggested that an increase in arginase may lead to decreased availability of arginine for nitric oxide synthase and may contribute to the remodeling of the lung.

The protective effect of vitamin C, vitamin E and selenium combination therapy on ethanol-induced duodenal mucosal injury

2004 ◽  
Vol 23 (8) ◽  
pp. 391-398 ◽  
Author(s):  
M Koyuturk ◽  
S Bolkent ◽  
S Ozdil ◽  
S Arbak ◽  
R Yanardag
Keyword(s):  
Nitric Oxide ◽  
Vitamin E ◽  
Nitric Oxide Synthase ◽  
Vitamin C ◽  
Protective Effect ◽  
Neuronal Nitric Oxide Synthase ◽  
Mucosal Injury ◽  
The Other ◽  
Absolute Ethanol ◽  
Oxide Synthase

In this study, the effect of a combination of vitamin C, vitamin E and selenium on ethanol-induced duodenal mucosal damage in rats was investigated morphologi-cally and biochemically. The duodenal mucosal injury was produced by oral administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg) and selenium (0.5 mg/kg) for 3 days and absolute ethanol 1 hour after last antioxidant administration and were sacrificed 1 hour after absolute ethanol. Extreme degeneration in intestinal mucosa of rats given ethanol was observed morphologically. In addition, an increase in neuronal nitric oxide synthase immunoreactive areas was observed in the rats of the group given ethanol. On the other hand, a normal morphological appearance and a decrease in neuronal nitric oxide synthase immunoreactive areas were detected in the rats given ethanol+vitamin C+vitamin E+selenium. In the group to which ethanol was administered, an increase in serum cholesterol and a decrease in serum albumin levels were determined. On the other hand, in the group to which ethanol+vitamin C+vitamin E+selenium were administered, serum cholesterol value decreased, and the serum albumin level increased. As a result, we can say that the combination of vitamin C, vitamin E and selenium has a protective effect on ethanolinduced duodenal mucosal injury.

scholarly journals INHIBITION OF TRANSCRIPTION FACTORS NF KAPPA B AND AP-1 LIMITS THE PROGRESSION OF OXIDATIVE-NITROSATIVE STRESS IN THE TISSUE OF CEREBRAL HEMISPHERES IN RATS AFTER MODELLED TRAUMATIC BRAIN INJURY

2020 ◽  
Vol 20 (1) ◽  
pp. 80-85 ◽  
Author(s):  
I.V. Yavtushenko ◽  
V.O. Kostenko
Keyword(s):  
Nitric Oxide ◽  
Traumatic Brain Injury ◽  
Transcription Factors ◽  
Brain Injury ◽  
Nitric Oxide Synthase ◽  
Nitrosative Stress ◽  
Cerebral Hemispheres ◽  
Male Rats ◽  
Nf Kappa B ◽  
Oxide Synthase

The study was aimed as investigating the effects of inhibitors of transcription factors NF kappa B and AP-1 activation on the development of oxidative-nitrosative stress in rat cerebral hemispheres following experimental traumatic brain injury (TBI). The study included 60 white Wistar male rats weighing 180-220 g, divided into 4 groups of 7 animals in each: the 1st group included pseudo-injured animals subjected to the same manipulations (ether anaesthesia, fixation) as the animals  in the experimental groups, except for TBI modelling, the 2nd group included the animals exposed to modelled TBI, the 3rd and 4th groups involved the rats who received ammonium pyrolidine dithiocarbamate, the nuclear translocation inhibitor NF kappa B in a dose of 76 mg/kg and the inhibitor AP-1 SR 11302 in a dose of 1 mg/kg, respectively for 7 days following the TBI modelling. On the 7th day after the simulation of a moderate TBI in rat cerebral hemisphere tissue, the following signs of oxidative-nitrosative stress have been detected: increased production of superoxide radical anion by NADPH and NADH-dependent electron transport chains, increased activity of nitric oxide synthase (total and inducible), a decrease and impairment of the coupling of its constitutive isoform, growth in the concentration of peroxynitrite, the development of decompensated lipid peroxidation. The application of transcription factor inhibitors NF kappa B (PDTC) and AP-1 (SR 11302) significantly reduces the signs of oxidative-nitrosative stress in the tissue of rat cerebral hemispheres on the 7th day of the experiment, reduces the production of superoxide anion radical and the activity of nitric oxide synthase (total and inducible), improves the coupling of its constitutive isoform, limits the peroxynitrite concentration, and enhances the antioxidant potential.

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