Melatonin modulates acute cardiac muscle damage induced by carbon tetrachloride – involvement of oxidative damage, glutathione, and arginine/NO metabolism

2020 ◽  
Author(s):  
Snezana Ćirić Zdravković ◽  
Tomislav Kostic ◽  
Zoran P Marcetić ◽  
Sulovic S Ljiljana ◽  
Biserka M Nedeljković ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Tetrachloride ◽  
Fas Ligand ◽  
Cardiac Tissue ◽  
Apoptosis Pathway ◽  
Starting Point ◽  
Extrinsic Apoptosis ◽  
Glutathione Cycle ◽  
Oxide Synthase ◽  
First Time

The present study was designed to evaluate the cardioprotective effects of melatonin (a single dose of 50 mg/kg), a naturally occurring polypharmacological molecule, in Wistar rats acutely exposed to carbon tetrachloride (CCl4). This was done for the first time by tracking different biochemical parameters that reflect rat heart antioxidative/oxidative capacities, nitric oxide/arginine metabolism, and glutathione cycle. Additionally, the extrinsic apoptosis pathway-related parameters were studied. Acute exposure to CCl4 led to an increase in the studied tissue oxidant parameters (hydrogen peroxide, malondialdehyde, carbonylated protein content), as well as the activity alteration of antioxidant (catalase, superoxide dismutase and peroxidase) and glutathione metabolizing (glutathione peroxidase, S-transferase and reductase) enzymes. Furthermore, CCl4 caused a disturbance in the tissue myeloperoxidase, nitric oxide, citrulline, arginase, and inducible nitric oxide synthase content/activities and two apoptosis-related parameters, caspase-3 and FAS ligand. Melatonin as a posttreatment prevented the changes induced by CCl4 to a differing extent and, in some cases, it was so potent that it completely abolished any tissue disturbances. This study is a promising starting point for further research directed to the development of melatonin treatment in cardiac tissue-associated diseases.

Increasing dihydrobiopterin causes dysfunction of endothelial nitric oxide synthase in rats in vivo

2011 ◽  
Vol 301 (3) ◽  
pp. H721-H729 ◽  
Author(s):  
Katsuhiko Noguchi ◽  
Naobumi Hamadate ◽  
Toshihiro Matsuzaki ◽  
Mayuko Sakanashi ◽  
Junko Nakasone ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Control Treatment ◽  
Enos Uncoupling ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
First Time

An elevation of oxidized forms of tetrahydrobiopterin (BH4), especially dihydrobiopterin (BH2), has been reported in the setting of oxidative stress, such as arteriosclerotic/atherosclerotic disorders, where endothelial nitric oxide synthase (eNOS) is dysfunctional, but the role of BH2 in the regulation of eNOS activity in vivo remains to be evaluated. This study was designed to clarify whether increasing BH2 concentration causes endothelial dysfunction in rats. To increase vascular BH2 levels, the BH2 precursor sepiapterin (SEP) was intravenously given after the administration of the specific dihydrofolate reductase inhibitor methotrexate (MTX) to block intracellular conversion of BH2 to BH4. MTX/SEP treatment did not significantly affect aortic BH4 levels compared with control treatment. However, MTX/SEP treatment markedly augmented aortic BH2 levels (291.1 ± 29.2 vs. 33.4 ± 6.4 pmol/g, P < 0.01) in association with moderate hypertension. Treatment with MTX alone did not significantly alter blood pressure or BH4 levels but decreased the BH4-to-BH2 ratio. Treatment with MTX/SEP, but not with MTX alone, impaired ACh-induced vasodilator and depressor responses compared with the control treatment (both P < 0.05) and also aggravated ACh-induced endothelium-dependent relaxations ( P < 0.05) of isolated aortas without affecting sodium nitroprusside-induced endothelium-independent relaxations. Importantly, MTX/SEP treatment significantly enhanced aortic superoxide production, which was diminished by NOS inhibitor treatment, and the impaired ACh-induced relaxations were reversed with SOD ( P < 0.05), suggesting the involvement of eNOS uncoupling. These results indicate, for the first time, that increasing BH2 causes eNOS dysfunction in vivo even in the absence of BH4 deficiency, demonstrating a novel insight into the regulation of endothelial function.

NO nerves in a tapeworm. NADPH-diaphorase histochemistry in adult Hymenolepis diminuta

Parasitology ◽  
1996 ◽  
Vol 113 (6) ◽  
pp. 559-565 ◽  
Author(s):  
M. K. S. Gustafsson ◽  
A. M. Lindholm ◽  
N. B. Terenina ◽  
M. Reuter
Keyword(s):  
Nitric Oxide ◽  
Nervous System ◽  
Nadph Diaphorase ◽  
Hymenolepis Diminuta ◽  
Staining Reaction ◽  
Internal Seminal Vesicle ◽  
Oxide Synthase ◽  
First Time ◽  
The Brain ◽  
Nerve Cords

SUMMARYThe free radical nitric oxide (NO), which is synthesized by nitric oxide synthase (NOS), has recently been discovered to function as a neuronal messenger. The presence of NOS was detected in the nervous system of adult Hymenolepis diminuta with NADPH-diaphorase (NADPH-d) histochemistry. The NADPH-d histochemical reaction is regarded as a selective marker for NOS in neuronal tissue. NADPH-d staining was observed in nerve fibres in the main and minor nerve cords and the transverse ring commissures, and in cell bodies in the brain commissure, along the main nerve cords, in the suckers and the rostellar sac. NADPH-d staining was also observed in the wall of the internal seminal vesicle and the genital atrium. The pattern of NADPH-d staining was compared with that of the 5-HT immunoreactive nervous elements. The NADPH-d staining reaction and the 5-HT immunoreactivity occur in separate sets of neurons. This is the first time the NADPH-d reaction has been demonstrated in the nervous system of a flatworm, indicating that NOS is present and that NO can be produced at this level of evolution.

Abstract 18060: TRAIL Promotes Angiogenesis and Ischemia-Induced Neovascularisation via NOX4, H2O2 and Nitric Oxide-Dependent Mechanisms

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Belinda A Di Bartolo ◽  
Sian P Cartland ◽  
Leonel Prado-Lourenco ◽  
Nor Saadah M Azahri ◽  
Thuan Thai ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiogenic Factor ◽  
Tubule Formation ◽  
Nitric Oxide Synthase Inhibitor ◽  
Therapeutic Implications ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
First Time

Background: Angiogenesis and neovascularization are essential processes that follow ischemia insults. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) not only induces endothelial cell (EC) death and inhibits angiogenesis, but also promotes EC migration, invasion and proliferation in vitro . These seemingly opposite effects make its role in angiogenesis in vivo unclear. Using TRAIL -/- and wild-type mice, we sought to determine the role of TRAIL in angiogenesis and neovascularisation. We also sought mechanisms in vitro . Methods and Results: Reduced vascularisation assessed by real-time in vivo 3D Vevo ultrasound imaging and CD31 staining was observed in TRAIL -/- mice 28 d after hindlimb ischemia. Moreover, reduced capillary formation and increased apoptosis was evident in TRAIL -/- muscles even at 3 d after ischemic surgery. We have previously shown that fibroblast growth factor-2 (FGF-2), a potent angiogenic factor, regulates TRAIL gene expression in vascular smooth muscle cells. Indeed, FGF-2 also regulates TRAIL expression in ECs, and FGF-2-inducible proliferation, migration and tubule formation was inhibited with siRNA targeting TRAIL. Notably, both FGF-2 and TRAIL significantly increased NOX4 expression. TRAIL-inducible angiogenic activity in ECs was inhibited with siRNAs targeting NOX4, and consistent with these, NOX4 mRNA was reduced in 3 d ischemic hindlimbs of TRAIL -/- mice. TRAIL stimulated intracellular H 2 O 2 levels in ECs, and TRAIL-inducible proliferation, migration and tubule formation was inhibited with not only PEG-catalase, a H 2 O 2 scavenger, but also blocked with L-NAME, a nitric oxide synthase inhibitor. Conclusions: This is the first demonstration showing that TRAIL promotes angiogenesis in vivo . We show for the first time that the TRAIL stimulates NOX4 expression to mediate nitric oxide-dependent angiogenic effects. This has significant therapeutic implications such that TRAIL may improve the angiogenic response to ischemia and increase perfusion recovery in patients with CVD and diabetes.

3.P.381 Expression of inducible nitric oxide synthase induces apoptosis mediated Fas and Fas ligand mechanism

1997 ◽  
Vol 134 (1-2) ◽  
pp. 279
Author(s):  
Teiji Esaki ◽  
Toshio Hayashi ◽  
Emiko Muto ◽  
Hatsuyo Kano ◽  
Thakur Navin Kumar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Fas Ligand ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The inducible nitric oxide synthase in vascular and cardiac tissue

1999 ◽  
Vol 375 (1-3) ◽  
pp. 139-155 ◽  
Author(s):  
Jean-Claude Stoclet ◽  
Bernard Muller ◽  
Katalin György ◽  
Ramaroson Andriantsiothaina ◽  
Andrei L Kleschyov
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Cardiac Tissue ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Characterisation of cocaine- and amphetamine- regulated transcript-like immunoreactive (CART-LI) enteric neurons in the porcine small intestine

2012 ◽  
Vol 60 (3) ◽  
pp. 371-381 ◽  
Author(s):  
Joanna Wojtkiewicz ◽  
Sławomir Gonkowski ◽  
Marek Bladowski ◽  
Mariusz Majewski
Keyword(s):  
Nitric Oxide ◽  
Small Intestine ◽  
The Other ◽  
Enteric Neurons ◽  
Double Labelling ◽  
Immunofluorescence Technique ◽  
Submucous Plexus ◽  
Oxide Synthase ◽  
First Time ◽  
Labelling Immunofluorescence

The aim of this study was to investigate the distribution and the number of cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) neurons and the co-localisation of CART with substance P (SP), somatostatin (SOM), nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) within the enteric nervous system (ENS) in the porcine small intestine. Accordingly, the myenteric plexus (MP), outer submucous plexus (OSP) and inner submucous plexus (ISP) of the small intestine (duodenum, jejunum and ileum) were studied by double-labelling immunofluorescence technique. CART-LI neurons were observed in all gut fragments and all types of intramural plexuses studied and amounted from 0.2 ± 0.1% in the ISP of ileum to 22.4 ± 2.4% in the MP of this segment. The co-localisation of CART and NOS or/and VIP was observed depending on the segment of the gut and the complexity of the intramural plexus. On the other hand, during this study the co-localisation of CART and SOM or/and SP was not observed. The present study, for the first time, presents a detailed description of the CART distribution pattern and co-localisation with other neuromodulators within the ENS of the porcine small intestine.

scholarly journals The N-terminal portion of autoinhibitory element modulates human endothelial nitric-oxide synthase activity through coordinated controls of phosphorylation at Thr495 and Ser1177

2014 ◽  
Vol 34 (4) ◽  
Author(s):  
Pei-Rung Wu ◽  
Bo-Rui Chen ◽  
Chi-Chun Hsieh ◽  
Wei-Chung Lin ◽  
Kenneth K. Wu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Regulatory Function ◽  
Terminal Portion ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
First Time ◽  
Nitric Oxide Synthase Activity

Our findings demonstrate for the first time that AIE insert exerts its regulatory function by coordinate phosphorylation on eNOS Ser1177 and Thr495, highlighting the importance of AIE in regulating agonist-induced eNOS activation.

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