scholarly journals Nitroaromatic Antibiotics as Nitrogen Oxide Sources

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 267
Author(s):  
Allison M. Rice ◽  
Yueming Long ◽  
S. Bruce King

Nitroaromatic antibiotics show activity against anaerobic bacteria and parasites, finding use in the treatment of Heliobacter pylori infections, tuberculosis, trichomoniasis, human African trypanosomiasis, Chagas disease and leishmaniasis. Despite this activity and a clear need for the development of new treatments for these conditions, the associated toxicity and lack of clear mechanisms of action have limited their therapeutic development. Nitroaromatic antibiotics require reductive bioactivation for activity and this reductive metabolism can convert the nitro group to nitric oxide (NO) or a related reactive nitrogen species (RNS). As nitric oxide plays important roles in the defensive immune response to bacterial infection through both signaling and redox-mediated pathways, defining controlled NO generation pathways from these antibiotics would allow the design of new therapeutics. This review focuses on the release of nitrogen oxide species from various nitroaromatic antibiotics to portend the increased ability for these compounds to positively impact infectious disease treatment.

Nanoscale ◽  
2021 ◽  
Author(s):  
Rachael Knoblauch ◽  
Chris Geddes

While the utility of reactive oxygen species in photodynamic therapies for both cancer treatments and antimicrobial applications has received much attention, the inherent potential of reactive nitrogen species (RNS) including...


Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5843
Author(s):  
Shaila Mehwish ◽  
Sanjay Varikuti ◽  
Mubarak Ali Khan ◽  
Tariq Khan ◽  
Imdad Ullah Khan ◽  
...  

Natural products from plants contain many interesting biomolecules. Among them, quercetin (Q), gallic acid (GA), and rutin (R) all have well-reported antileishmanial activity; however, their exact mechanisms of action are still not known. The current study is a step forward towards unveil the possible modes of action of these compounds against Leishmania donovani (the causative agent of visceral leishmaniasis). The selected compounds were checked for their mechanisms of action against L. donovani using different biological assays including apoptosis and necrosis evaluation, effects on genetic material (DNA), quantitative testing of nitric oxide production, ultrastructural modification via transmission electron microscopy, and real-time PCR analysis. The results confirmed that these compounds are active against L. donovani, with IC50 values of 84.65 µg/mL, 86 µg/mL, and 98 µg/mL for Q, GA, and R, respectively. These compounds increased nitric oxide production and caused apoptosis and DNA damage, which led to changes in the treated cells’ ultrastructural behavior and finally to the death of L. donovani. These compounds also suppressed essential enzymes like trypanothione reductase and trypanothione synthetase, which are critical for leishmanial survival. The selected compounds have high antileishmanial potentials, and thus in-vivo testing and further screening are highly recommended.


2020 ◽  
Vol 12 (2) ◽  
pp. 187-195
Author(s):  
Halyna Kopylchuk ◽  
Ivanna Nykolaichuk ◽  
Olesiia Kuziak

This paper presents studies of nitric oxide and low-molecular S-nitrosothiols in the mitochondrial and cytosolic fractions of the rats' liver under the conditions of, alimentary protein deprivation, consumption of excess sucrose content and combined action of two adverse factors. In order to model the low-protein diet of the animal for 28 days received an isocaloric diet containing 4.7% protein, 10% fat, 81,3% carbohydrates (starch – 37%, sucrose – 30%, cellulose – 5%) and was calculated in accordance with the recommendations of the American Institute of Nutrition. The high-sugar diet consisted of 14% protein, 10% fat, 72% carbohydrates (starch – 37%, sucrose – 30%, cellulose – 5%). The mitochondrial and cytosolic fraction of rat liver cells were obtained by the method of differential centrifugation. Nitrogen oxide content was assessed by a unified method by determining the NO2- content, which is a stable metabolite of nitric oxide. Since NO is inactivated into an oxidase reaction with the conversion into nitrite or nitrate that is quickly metabolized, the nitrogen oxide content was assessed by the change in NO2-. The concentration of S-nitrosothiols was recorded, respectively, by determining the concentration of nitrite anion before and after the addition of Hg2+ ions, which by modifying the S – N bonds catalyzes the release of S-nitrosyl thiols of nitric oxide. An increase in NO content in both hepatic subcellular fractions of the rats’ experimental groups compared to control values was found. However, a lack of protein in the diet (protein deficiency in the diet leads to an increase in nitric oxide levels in 3-4 times) can be considered as a key factor in the recorded changes in the mitochondria of the animals’ liver, while in the cytosol - excessive consumption of sucrose (3-5 times increase). Regarding the level of S-nitrosothiols, in the studied fractions, multidirectional changes in their concentration were found. Thus, an increase in the content of nitrosyl derivatives in the mitochondria of rat’s liver cells with a simultaneous decrease in their level in the cytosol indicates dysmetabolic disorders in the transport system and deposition of nitric oxide, which can lead to the development of nitrosative stress under the experimental conditions.


2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Yuchuan Liu ◽  
Abdelkarim Sabri ◽  
Louis Dell'Italia ◽  
Victor Rizzo ◽  
Emily J Tsai

Volume-overload (VO), as seen in regurgitant valvular disease, large myocardial infarction, and severe cardiac systolic dysfunction, triggers eccentric hypertrophy. Given that nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) modulate cardiomyocyte hypertrophy, apoptosis, and cardioprotection, differential regulation of these signals may distinguish eccentric from the more commonly studied concentric hypertrophy. We recently showed that pressure-overload (PO) induces relocalization and oxidation of the NO receptor soluble guanylyl cyclase (sGC), thereby diminishing cyclase activity and cGMP cardioprotection. The effects of volume-overload on NO and cGMP signaling are unknown. We tested the hypothesis that VO induces relocalization but not oxidation of sGC, thereby disrupting spatial regulation of NO-cGMP signaling without depressing cyclase activity. Volume-overload was established by chordal rupture-induced mitral regurgitation in dogs. We compared intracellular localization and activity of sGC in VO and control LVs (N=5 per group). Both sGC subunits were detected within and outside of caveolae-enriched lipid raft microdomains (Cav3+LR). In VO hearts, sGCβ1 fell in expression by nearly 50% and relocalized away from Cav3+LR to non-lipid raft microdomains (NLR). Despite VO-induced sGCβ1 changes, overall NO-stimulated sGC activity was preserved. An enhanced response to heme/NO-independent sGC activator BAY 60-2770 suggested that a subset of sGC was heme-oxidized in VO hearts, though to a much lesser degree than in PO hearts. As in PO hearts, Cav3+LR appear to protect sGC from heme-oxidation in VO hearts. Initial study of downstream reactive nitrogen species (RNS) and cGMP signaling supported our theory that VO altered spatial regulation of NO-cGMP signaling. Also, a trend towards increased overall tyrosine-nitration, predominantly within NLR, was observed in VO hearts. Volume-overload shifted cardiac NO-cGMP signaling from Cav3+LR to NLR microdomains without depressing NO/heme-dependent sGC activation. These findings suggest that differential spatial regulation of NO/RNS signaling, rather than simply increased RNS signaling, might drive the distinct molecular pathophysiology of eccentric hypertrophy.


1991 ◽  
Vol 12 (suppl E) ◽  
pp. 16-24 ◽  
Author(s):  
W. R. Kukovetz ◽  
S. Holzmann ◽  
K. Schmidt

Author(s):  
S. P. Seto ◽  
T. F. Lyon

The exhaust plumes of modern military engines can be rendered visible at low augmentor power operation by the presence of nitrogen dioxide (NO2). Visible plumes have also been observed from some industrial gas turbines that have duct burners downstream of the power turbines. In 1986, gaseous emissions measurements were taken behind two F101 turbofan engines to determine the effect of reheat level on the degree of conversion of nitric oxide (NO) to nitrogen dioxide and to relate the plume visibility to nitrogen dioxide concentration.


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