Analysis of the content of nitric oxide (II) metabolites rats of different ages

2021 ◽  
Author(s):  
Y.I. Belova ◽  
O.V. Yakovleva

Nitrogen monoxide is a gas transmitter that is an important intermediary in many organ systems, especially in the central nervous system. Nitrogen monoxide is involved in the relaxation of smooth vascular muscles, activation of neurons and responsible for the cytotoxicity of macrophages. The study of change nitrogen oxide metabolite concentration helps to determine its effects on human and animal organs. The study was carried out on laboratory animals of different ages. We used a spectrophotometric method to determine the level of metabolites based on the reaction of nitrites to the Griss reagent. We noted that the maximum level of metabolites NO was observed in newborn animals at the age of 4 days. In addition, metabolite concentrations decreased gradually by 14-15 days of life, reaching a minimum of 30 days Key words: nitrogen monoxide, rats, age, metabolites of nitrogen monoxide, spectrophotometry.

2012 ◽  
Vol 64 (3) ◽  
pp. 1207-1216 ◽  
Author(s):  
D. Hrncic ◽  
Aleksandra Rasic-Markovic ◽  
Jelica Bjekic-Macut ◽  
Veselinka Susic ◽  
D. Mladenovic ◽  
...  

Epilepsy is one of the leading neurological disorders and affects 1-2% of the world?s population. Generally, it is a result of an imbalance between excitatory and inhibitory phenomena in the central nervous system (CNS), but the mechanisms of its initiation and propagation still require further investigations. Experimental models represent one of the most powerful tools to better understand the mechanisms of epileptogenesis. Nitric oxide (NO) is gaseous molecule with pleiotropic physiological and pathological effects in almost all organ systems and intriguing biological relevance, especially in the CNS where it acts as a gaseous neurotransmitter. The role of NO in the generation of epilepsy is highly contradictory, since there is evidence of its anticonvulsive, as well as proconvulsive properties. Therefore, we will discuss in this review the involvement of NO-mediated signaling pathways in the mechanisms of epileptogenesis, taking into account the findings revealed in experimental studies on animal models of epilepsy.


Author(s):  
E. K. Rakhmatullin ◽  
O. D. Sklyarov

Preclinical study of the drugs toxicity was analysed it allows predicting the safety of veterinary drugs in laboratory animals. The fundamental normative instruments in the field of preclinical study of drugs for veterinary medicine and animal husbandry are Order of the Ministry of Agriculture of the Russian Federation dated 06.03.2018 N 101 and GOST 33044-2014 Principles of Good Laboratory Practice. An important indicator of the preclinical study of the veterinary drugs is the determination (calculation) of median lethal dose value (lethal dose for half of the animals tested) or concentration (LD50 or LC50). Existing methods for determining this indicator make it possible at the initial study stage to determine the degree and class the drug of toxicity. Studying the symptoms of intoxication in the analysis of pharmacological substances one obtains significant information about the nature of the action of the future drug. The clinical manifestations of intoxication with damage to various organ systems are presented. As criteria for assessing the toxic effects of veterinary drugs it is recommended to determine LD50, cumulation coefficient, latitude index of therapeutic effects, dose level of toxic effects in the experiment which allows predicting the nature and degree of toxic effects of the drug even at the stage of preclinical veterinary drugs study.


Author(s):  
Christian Muschitz ◽  
Anita Trummert ◽  
Theresa Berent ◽  
Norbert Laimer ◽  
Lukas Knoblich ◽  
...  

SummarySevere acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), produces protean manifestations and causes indiscriminate havoc in multiple organ systems. This rapid and vast production of proinflammatory cytokines contributes to a condition termed cytokine storm. A 35-year-old, otherwise healthy, employed, male patient was tested positive for COVID-19. He was admitted to the hospital on disease day 10 due to retarded verbal reactions and progressive delirium. On account of these conditions and the need for noninvasive/invasive ventilation, a combination treatment with baricitinib and remdesivir in conjunction with standard of care was initiated. The cytokine storm was rapidly blocked, leading to a vast pulmonary recovery with retarded recovery of the central nervous system. We conclude that the rapid blockade of the COVID-19-induced cytokine storm should be considered of avail as a principle of careful decision-making for effective recovery.


2011 ◽  
Vol 300 (1) ◽  
pp. C58-C64 ◽  
Author(s):  
Rui-Fang Yang ◽  
Jing-Xiang Yin ◽  
Yu-Long Li ◽  
Matthew C. Zimmerman ◽  
Harold D. Schultz

Actions of angiotensin-(1–7) [Ang-(1–7)], a heptapeptide of the renin-angiotensin system, in the periphery are mediated, at least in part, by activation of nitric oxide (NO) synthase (NOS) and generation NO·. Studies of the central nervous system have shown that NO· acts as a sympathoinhibitory molecule and thus may play a protective role in neurocardiovascular diseases associated with sympathoexcitation, such as hypertension and heart failure. However, the contribution of NO in the intraneuronal signaling pathway of Ang-(1–7) and the subsequent modulation of neuronal activity remains unclear. Here, we tested the hypothesis that neuronal NOS (nNOS)-derived NO· mediates changes in neuronal activity following Ang-(1–7) stimulation. For these studies, we used differentiated catecholaminergic (CATH.a) neurons, which we show express the Ang-(1–7) receptor (Mas R) and nNOS. Stimulation of CATH.a neurons with Ang-(1–7) (100 nM) increased intracellular NO levels, as measured by 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate (DAF-FM) fluorescence and confocal microscopy. This response was significantly attenuated in neurons pretreated with the Mas R antagonist (A-779), a nonspecific NOS inhibitor (nitro-l-arginine methyl ester), or an nNOS inhibitor ( S-methyl-l-thiocitrulline, SMTC), but not by endothelial NOS (eNOS) or inhibitory NOS (iNOS) inhibition {l- N-5-(1-iminoethyl)ornithine (l-NIO) and 1400W, respectively}. To examine the effect of Ang-(1–7)-NO· signaling on neuronal activity, we recorded voltage-gated outward K+ current ( IKv) in CATH.a neurons using the whole cell configuration of the patch-clamp technique. Ang-(1–7) significantly increased IKv, and this response was inhibited by A-779 or S-methyl-l-thiocitrulline, but not l-NIO or 1400W. These findings indicate that Ang-(1–7) is capable of increasing nNOS-derived NO· levels, which in turn, activates hyperpolarizing IKv in catecholaminergic neurons.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Srinivas Sriramula ◽  
Huijing Xia ◽  
Eric Lazartigues

Elevated reactive oxygen species (ROS) in the central nervous system (CNS) through NADPH oxidase and diminished Nitric oxide (NO) levels are involved in the pathogenesis of hypertension. We previously reported that central Angiotensin Converting Enzyme 2 (ACE2) overexpression prevents the development of hypertension induced by DOCA-salt in a transgenic mouse model (syn-hACE2; SA) with human ACE2 targeted selectively to neurons in the CNS. While baseline blood pressure (BP; telemetry) was not different among genotypes, DOCA-salt treatment (1mg/g body wt DOCA, 1% saline in drinking water for 3 weeks) resulted in significantly lower BP level in SA mice (122 ±3 mmHg, n=12) compared to non-transgenic (NT) littermates (138 ±3 mmHg, n=8). To elucidate the mechanisms involved in this response, we investigated the paraventricular nucleus (PVN) expression of Nox-2 (catalytic subunit of NADPH oxidase), 3-nitrotyrosine, and endothelial nitric oxide synthase (eNOS) and anti-oxidant enzymes superoxide dismutase (SOD) and catalase in the hypothalamus. DOCA-salt treatment resulted in decreased catalase (95.2 ±5.6 vs. 113.8 ±17.6 mmol/min/ml, p<0.05) and SOD (4.1 ±0.4 vs. 5.9 ±0.2 U/ml, p<0.01) activities in hypothalamic homogenates of NT mice, which was prevented by ACE2 overexpression (141.8 ±9.9 vs. 142.1 ±9.2 mmol/min/ml and 5.9 ±0.3 vs. 7.9 ±0.2 U/ml, respectively). NT mice treated with DOCA-salt showed increased oxidative stress as indicated by increased expression of Nox-2 (61 ±5 % increase, n=9, p<0.001 vs. NT) and 3-nitrotyrosine (89 ±32 % increase, n=9, p<0.01 vs. NT) in the PVN which was attenuated in SA mice. Furthermore, DOCA-salt hypertension resulted in decreased phosphorylation of eNOS-ser1177 in the PVN (33 ±5 % decrease, n=9, p<0.05 vs NT) and this decrease was prevented by ACE2 overexpression. Taken together, these data provide evidence that brain ACE2 regulates the balance between NO and ROS levels, thereby preventing the development of DOCA-salt hypertension.


2021 ◽  
Vol 21 (2) ◽  
pp. 63-73
Author(s):  
Valeria A. Razenkova ◽  
Dmitrii E. Korzhevskii

BACKGROUND: Taking into account the importance of GABAergic brain system research and also the opportunity to achieve specific and accurate results in laboratory studies using immunohistochemical approaches, it seems important to have a reliable method of visualization GABA-synthesizing cells, their projections and synapses, for the morphofunctional analysis of GABAergic system both in normal conditions and in the experimental pathology. AIM: The aim of the study was to visualize analyze GABAergic neurons and synapses within rats brain using three different antibody types against glutamate decarboxylase and to identify the optimal conditions for reaction performing. MATERIALS AND METHODS: The study was performed on paraffin brain tissue sections of 5 adult Wistar rats. Immunohistochemical reactions using three antibody types against glutamate decarboxylase isoform 67 (GAD67) and glutamate decarboxylase isoform 65 (GAD65) were performed. Additional controls on C57/Bl6 mice and Chinchilla rabbits brain samples were also carried out. RESULTS: Antibodies used in the research made it possible to achieve high quality of GABAergic structures visualizing without increasing background staining. At the same time different antibody types are distinct in their efficacy to perform immunohistochemistry reaction on laboratory animal brain tissue samples. By performing additional controls, we discovered that there is necessary to adsorb secondary reagents immunoglobulins in order to eliminate nonspecific staining. It was found that GAD67 and GAD65 distribution in rat forebrain structures is different. It was stated that GAD67 immunohistochemistry most completely reveals GABAergic brain structures compared to GAD65 immunhistochemistry. The possibility of determining morphological features of GABAergic neurons and synaptic terminals, as well as performing quantitative analysis, was demonstrated. CONCLUSIONS: The approach proposed makes it possible to specifically visualize GABAergic structures of the central nervous system of different laboratory animals. This could be useful both in fundamental studies and in pathology research.


2020 ◽  
pp. 56-62
Author(s):  
E.V. Filippova

In a chronopharmacological experiment, the effect of two drugs with psychotropic action in combinations on the behavior of laboratory animals subjected to chronic alcohol intoxication was examined. Against the background of a deprimating agent, a decrease in the threshold of sensitivity to electrical irritation and the duration of an aggressive reaction was revealed; an increase in these indicators was established with a combination of a deprimating drug with an antioxidant. It has been shown that the antioxidant has a desynchronizing effect on the behavioral reactions of laboratory animals for two days, which indicates a pronounced adaptive effect. In the case of using combinations of a deprimating agent with an antioxidant, a decrease in the destruction of the histological structure of the myocardium against the background of chronic alcoholization was established.


2017 ◽  
Vol 3 (3) ◽  
pp. 157
Author(s):  
M. Furutani ◽  
Y. Ohta ◽  
M. Nose

<p>Flat low-temperature two-stage flames were established on a Powling burner using rich diethyl-ether/ air or n-heptane/air mixtures, and nitrogen monoxide NO was added into the fuel-air mixtures with a concentration of 240 ppm. The temperature development and chemical-species histories, especially of NO, nitrogen dioxide NO<sub>2</sub> and hydrogen cyanide HCN were examined associated with an emission-spectrum measurement from the low-temperature flames. Nitrogen monoxide was consumed in the cool-flame region, where NO was converted to the NO<sub>2</sub>. The NO<sub>2</sub> generated, however, fell suddenly in the cool-flame degenerate region, in which the HCN superseded. In the blue-flame region the NO came out again and developed accompanied with remained HCN in the post blue-flame region. The NO seeding into the mixture intensified the blue-flame luminescence probably due to the cyanide increase.</p>


2021 ◽  
Author(s):  
Bashaer Abu Khatir ◽  
Gordon Omar Davis ◽  
Mariam Sameem ◽  
Rutu Patel ◽  
Jackie Fong ◽  
...  

Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex, and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, lead to the formation of tumors and developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro. Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that Tuberin levels remain stable in the olfactory bulb but decrease in the Purkinje cell layer during embryonic mouse brain development. We show here that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. These data provide support for the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.


Sign in / Sign up

Export Citation Format

Share Document