Mode of Action of Anti-Infective Agents Focus on Oxidative Stress and Electron Transfer

2000 ◽  
Vol 6 (2) ◽  
pp. 143-167 ◽  
Author(s):  
Peter Kovacic ◽  
Laura Becvar
Keyword(s):  
Oxidative Stress ◽  
Electron Transfer ◽  
Mode Of Action

scholarly journals Unifying Mechanism for Nutrients as Anticancer Agents: Electron Transfer, Reactive Oxygen Species and Oxidative Stress

2017 ◽  
Vol 9 (8) ◽  
pp. 66 ◽  
Author(s):  
Peter Kovacic ◽  
Ratnasamy Somanathan
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Electron Transfer ◽  
Anticancer Agents ◽  
Mode Of Action ◽  
Recent Article ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Bactericidal Action ◽  
And Oxidative Stress

A recent article deals with various nutrients in relation to bactericidal action. The present article focuses on a unifying mode of action for the nutrients, namely, resveratrol, epigallocatechin, polyene-ß-carotene, polyene lycopene, piperine, curcumin, genistein, luteolin, sulforaphane and pomegranate extract. The mechanism is based on electron transfer, reactive oxygen species and oxidative stress, which comprises an extension of earlier reports involving agents. Most of the compounds are precursors of electron transfer quinones, whereas others fit into the polyene category. The nutrients are better known as antioxidants. The dichotomy is addressed.

scholarly journals Cultivation at high osmotic pressure confers ubiquinone 8–independent protection of respiration on Escherichia coli

2019 ◽  
Vol 295 (4) ◽  
pp. 981-993 ◽  
Author(s):  
Laura Tempelhagen ◽  
Anita Ayer ◽  
Doreen E. Culham ◽  
Roland Stocker ◽  
Janet M. Wood
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Escherichia Coli ◽  
Electron Transfer ◽  
Oxygen Uptake ◽  
Osmotic Pressure ◽  
Respiratory Chain ◽  
Membrane Lipid ◽  
E Coli ◽  
Uptake Rates

Ubiquinone 8 (coenzyme Q8 or Q8) mediates electron transfer within the aerobic respiratory chain, mitigates oxidative stress, and contributes to gene expression in Escherichia coli. In addition, Q8 was proposed to confer bacterial osmotolerance by accumulating during growth at high osmotic pressure and altering membrane stability. The osmolyte trehalose and membrane lipid cardiolipin accumulate in E. coli cells cultivated at high osmotic pressure. Here, Q8 deficiency impaired E. coli growth at low osmotic pressure and rendered growth osmotically sensitive. The Q8 deficiency impeded cellular O2 uptake and also inhibited the activities of two proton symporters, the osmosensing transporter ProP and the lactose transporter LacY. Q8 supplementation decreased membrane fluidity in liposomes, but did not affect ProP activity in proteoliposomes, which is respiration-independent. Liposomes and proteoliposomes prepared with E. coli lipids were used for these experiments. Similar oxygen uptake rates were observed for bacteria cultivated at low and high osmotic pressures. In contrast, respiration was dramatically inhibited when bacteria grown at the same low osmotic pressure were shifted to high osmotic pressure. Thus, respiration was restored during prolonged growth of E. coli at high osmotic pressure. Of note, bacteria cultivated at low and high osmotic pressures had similar Q8 concentrations. The protection of respiration was neither diminished by cardiolipin deficiency nor conferred by trehalose overproduction during growth at low osmotic pressure, but rather might be achieved by Q8-independent respiratory chain remodeling. We conclude that osmotolerance is conferred through Q8-independent protection of respiration, not by altering physical properties of the membrane.

scholarly journals Cynara cardunculus Crude Extract as a Powerful Natural Herbicide and Insight into the Mode of Action of Its Bioactive Molecules

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 209 ◽  
Author(s):  
Sofiene Ben Kaab ◽  
Laurence Lins ◽  
Marwa Hanafi ◽  
Iness Bettaieb Rebey ◽  
Magali Deleu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Bioactive Compounds ◽  
Crude Extract ◽  
Mode Of Action ◽  
Dry Weight ◽  
Herbicidal Activity ◽  
Bioactive Molecules ◽  
Cynara Cardunculus ◽  
Initial Interaction ◽  
Negative Impacts

The use of chemical herbicides could not only potentially induce negative impacts on the environment, animals, and human health, but also increase the weed resistance to herbicides. In this context, the use of plant extracts could be an interesting and natural alternative to chemical products. It is important to understand the mode of action of their bioactive compounds. This is why we have studied the herbicidal effect of Cynara cardunculus crude extract in terms of inhibition of weeds’ seedling growth and its impact on physiological parameters of treated plantlets, like conductivity, dry weight, and fluorescence, and biochemical parameters linked to oxidative stress. We have observed that C. cardunculus crude extract induces oxidative stress in the treated plants and consequently disturbs the physiological and biochemical functions of the plant cells. We have investigated the herbicidal activity of three bioactive compounds, naringenin, myricitrin, and quercetin, from the C. cardunculus crude extract. In both pre- and post-emergence trials, naringenin and myricitrin were significantly more phytotoxic than quercetin. We suggest that their differential initial interaction with the plant’s plasma membrane could be one of the main signals for electrolyte leakage and production of high levels of phenoxyl radicals.

scholarly journals The Effect of Lithium on Inflammation-Associated Genes in Lipopolysaccharide-Activated Raw 264.7 Macrophages

2020 ◽  
Vol 2020 ◽  
pp. 1-18 ◽  
Author(s):  
Raymond T. Makola ◽  
Vusi G. Mbazima ◽  
Matlou P. Mokgotho ◽  
Vincent S. Gallicchio ◽  
Thabe M. Matsebatlela
Keyword(s):  
Oxidative Stress ◽  
Mrna Expression ◽  
Mode Of Action ◽  
Nuclear Translocation ◽  
Glycogen Synthase ◽  
Bipolar Disorders ◽  
No Production ◽  
Raw 264.7 ◽  
Activated Macrophages ◽  
Raw 264.7 Macrophages

Lithium remains the preferred Food and Drug Administration- (FDA-) approved psychiatric drug for treatment of bipolar disorders since its medical establishment more than half a century ago. Recent studies revealed a promising role for lithium in the regulation of inflammation, oxidative stress, and neurodegeneration albeit unclear about its exact mode of action. Thus, the intention of this study is to delineate the regulatory mechanisms of lithium on oxidative stress in lipopolysaccharide- (LPS-) activated macrophages by evaluating its effects on nuclear factor-κB (NF-κB) activity and mRNA expression of multiple oxidative stress-related NF-κB genes. Raw 264.7 macrophages were treated with up to 10 mM lithium, and no change in cell proliferation, viability, growth, and cell adhesion was observed in real time. Pretreatment with low doses of lithium was shown to reduce nitric oxide (NO) production in LPS-activated macrophages. A reduced internal H2DCFDA fluorescence intensity, indicative of reduced reactive oxygen species (ROS) production, was observed in LPS-activated Raw 264.7 macrophages treated with lithium. Lithium has been shown to lower the production of the chemokine RANTES; furthermore, this inhibitory action of lithium has been suggested to be independent of glycogen synthase kinase-3 β (GSK3β) activity. It is shown here that lithium modulates the expression of several inflammatory genes including IκB-α, TRAF3, Tollip, and NF-κB1/p50 which are regulators of the NF-κB pathway. Moreover, lithium inhibits NF-κB activity by lowering nuclear translocation of NF-κB in LPS-activated macrophages. This is the first study to associate Tollip, Traf-3, and IκB-α mRNA expression with lithium effect on NF-κB activity in LPS-activated Raw 264.7 macrophages. Although these effects were obtained using extratherapeutic concentrations of lithium, results of this study provide useful information towards understanding the mode of action of lithium. This study associates lithium with reduced oxidative stress in LPS-activated Raw 264.7 macrophages and further suggests candidate molecular targets for the regulation of oxidative stress-related diseases using lithium beyond bipolar disorders.

scholarly journals Activation of 3-Mercaptopyruvate Sulfurtransferase by Glutaredoxin Reducing System

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 826
Author(s):  
Noriyuki Nagahara
Keyword(s):  
Oxidative Stress ◽  
Electron Transfer ◽  
Glutathione Reductase ◽  
Nicotinamide Adenine Dinucleotide ◽  
Transfer Reaction ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Electron Transfer Reaction ◽  
Reduced Form ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Substrate Proteins

Glutaredoxin (EC 1.15–1.21) is known as an oxidoreductase that protects cysteine residues within proteins against oxidative stress. Glutaredoxin catalyzes an electron transfer reaction that donates an electron to substrate proteins in the reducing system composed of glutaredoxin, glutathione, glutathione reductase, and nicotinamide-adenine dinucleotide phosphate (reduced form). 3-mercaptopyruvate sulfurtransferase (EC 2.8.1.2) is a cysteine enzyme that catalyzes transsulfuration, and glutaredoxin activates 3-mercaptopyruvate sulfurtransferase in the reducing system. Interestingly, even when glutathione or glutathione reductase was absent, 3-mercaptopyruvate sulfurtransferase activity increased, probably because reduced glutaredoxin was partly present and able to activate 3-mercaptopyruvate sulfurtransferase until depletion. A study using mutant Escherichia coli glutaredoxin1 (Cys14 is the binding site of glutathione and was replaced with a Ser residue) confirmed these results. Some inconsistency was noted, and glutaredoxin with higher redox potential than either 3-mercaptopyruvate sulfurtransferase or glutathione reduced 3-mercaptopyruvate sulfurtransferase. However, electron-transfer enzymatically proceeded from glutaredoxin to 3-mercaptopyruvate sulfurtransferase.

scholarly journals Trypanocidal Activity of Melamine-Based Nitroheterocycles

2004 ◽  
Vol 48 (5) ◽  
pp. 1733-1738 ◽  
Author(s):  
Mhairi L. Stewart ◽  
Gorka Jimenez Bueno ◽  
Alessandro Baliani ◽  
Burkhard Klenke ◽  
Reto Brun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mammalian Cell ◽  
Mode Of Action ◽  
Genotoxic Effect ◽  
Null Mutant ◽  
Compound A ◽  
African Trypanosomes ◽  
Trypanocidal Activity ◽  
Adenosine Transport

ABSTRACT A series of nitroheterocyclic compounds were designed with linkages to melamine or benzamidine groups that are known substrates of the P2 aminopurine and other transporters in African trypanosomes of the brucei group. Several compounds showed in vitro trypanotoxicity with 50% inhibitory concentrations in the submicromolar range. Although most compounds interacted with the P2 transporter, as judged by their ability to inhibit adenosine transport via this carrier, uptake through this route was not necessary for activity since TbAT1-null mutant parasites, deficient in this transporter, retained sensitivity to these drugs. One compound, a melamine-linked nitrofuran, also showed pronounced activity against parasites in mice. Studies into the mode of action of this compound indicated that neither reductive, nor oxidative, stress were related to its trypanocidal activity ruling out a genotoxic effect in T. brucei, distinguishing it from some other, mammalian cell toxic, trypanocidal nitroheterocycles.

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