scholarly journals Redox Control of Multidrug Resistance and Its Possible Modulation by Antioxidants

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Aysegul Cort ◽  
Tomris Ozben ◽  
Luciano Saso ◽  
Chiara De Luca ◽  
Liudmila Korkina

Clinical efficacy of anticancer chemotherapies is dramatically hampered by multidrug resistance (MDR) dependent on inherited traits, acquired defence against toxins, and adaptive mechanisms mounting in tumours. There is overwhelming evidence that molecular events leading to MDR are regulated by redox mechanisms. For example, chemotherapeutics which overrun the first obstacle of redox-regulated cellular uptake channels (MDR1, MDR2, and MDR3) induce a concerted action of phase I/II metabolic enzymes with a temporal redox-regulated axis. This results in rapid metabolic transformation and elimination of a toxin. This metabolic axis is tightly interconnected with the inducible Nrf2-linked pathway, a key switch-on mechanism for upregulation of endogenous antioxidant enzymes and detoxifying systems. As a result, chemotherapeutics and cytotoxic by-products of their metabolism (ROS, hydroperoxides, and aldehydes) are inactivated and MDR occurs. On the other hand, tumour cells are capable of mounting an adaptive antioxidant response against ROS produced by chemotherapeutics and host immune cells. The multiple redox-dependent mechanisms involved in MDR prompted suggesting redox-active drugs (antioxidants and prooxidants) or inhibitors of inducible antioxidant defence as a novel approach to diminish MDR. Pitfalls and progress in this direction are discussed.

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Delira Robbins ◽  
Yunfeng Zhao

Recent studies have shown that antioxidant enzyme expression and activity are drastically reduced in most human skin diseases, leading to propagation of oxidative stress and continuous disease progression. However, antioxidants, an endogenous defense system against reactive oxygen species (ROS), can be induced by exogenous sources, resulting in protective effects against associated oxidative injury. Many studies have shown that the induction of antioxidants is an effective strategy to combat various disease states. In one approach, a SOD mimetic was applied topically to mouse skin in the two-stage skin carcinogenesis model. This method effectively reduced oxidative injury and proliferation without interfering with apoptosis. In another approach, Protandim, a combination of 5 well-studied medicinal plants, was given via dietary administration and significantly decreased tumor incidence and multiplicity by 33% and 57%, respectively. These studies suggest that alterations in antioxidant response may be a novel approach to chemoprevention. This paper focuses on how regulation of antioxidant expression and activity can be modulated in skin disease and the potential clinical implications of antioxidant-based therapies.


2010 ◽  
Vol 104 (10) ◽  
pp. 1492-1499 ◽  
Author(s):  
Helena Andersson ◽  
Anette Karlsen ◽  
Rune Blomhoff ◽  
Truls Raastad ◽  
Fawzi Kadi

Changes in plasma endogenous and dietary antioxidants and oxidative stress markers were studied following two 90 min elite female soccer games separated by 72 h of either active or passive recovery. The active recovery group (n 8) trained for 1 h at 22 and 46 h after the first game (low-intensity cycling and resistance training), while the passive group rested (n 8). Blood samples were taken before the games; immediately after the games; 21, 45 and 69 h after the first game; and immediately after the second game. The oxidative stress markers and antioxidants were not affected by active recovery. The oxidative stress marker GSSG increased by the same extent after both the games, while the lipid peroxidation marker diacron-reactive oxygen metabolite remained unchanged. The endogenous antioxidants total glutathione and uric acid and ferric reducing/antioxidant power increased immediately after both the games with the same amplitude, while increases in cysteine, cysteine–glycine and total thiols reached significant levels only after the second game. The changes in dietary antioxidants after the first game were either rapid and persistent (tocopherols and ascorbic acid (AA) increased; polyphenols decreased) or delayed (carotenoids). This resulted in high pre-second game levels of tocopherols, AA and carotenoids. Polyphenols returned to baseline at 69 h, and were not affected by the second game. In conclusion, the soccer-associated dietary antioxidant defence, but not the endogenous antioxidant defence, is persistent. Similar acute oxidative stress and endogenous antioxidant responses and dissimilar dietary antioxidant reactions occur during two repeated female soccer games. Finally, the complex antioxidant response to soccer is not affected by active recovery training.


2022 ◽  
Author(s):  
Ali A Kermani ◽  
Olive E. Burata ◽  
B Ben Koff ◽  
Akiko Koide ◽  
Shohei Koide ◽  
...  

Proteins from the bacterial small multidrug resistance (SMR) family are proton-coupled exporters of diverse antiseptics and antimicrobials, including polyaromatic cations and quaternary ammonium compounds. The transport mechanism of the Escherichia coli transporter, EmrE, has been studied extensively, but a lack of high-resolution structural information has impeded a structural description of its molecular mechanism. Here we apply a novel approach, multipurpose crystallization chaperones, to solve several structures of EmrE, including a 2.9 Å structure at low pH without substrate. We report five additional structures in complex with structurally diverse transported substrates, including quaternary phosphonium, quaternary ammonium, and planar polyaromatic compounds. These structures show that binding site tryptophan and glutamate residues adopt different rotamers to conform to disparate structures without requiring major rearrangements of the backbone structure. Structural and functional comparison to Gdx-Clo, an SMR protein that transports a much narrower spectrum of substrates, suggests that in EmrE, a relatively sparse hydrogen bond network among binding site residues permits increased sidechain flexibility.


2011 ◽  
Vol 7 (5) ◽  
pp. 1701 ◽  
Author(s):  
Avishek Ganguly ◽  
Soumya Basu ◽  
Kaushik Banerjee ◽  
Paramita Chakraborty ◽  
Avijit Sarkar ◽  
...  

Author(s):  
Sophie E. Darch ◽  
Dipankar Koley

Bacteria are often found in their natural habitats as spatially organized biofilm communities. While it is clear from recent work that the ability to organize into precise spatial structures is important for fitness of microbial communities, a significant gap exists in our understanding regarding the mechanisms bacteria use to adopt such physical distributions. Bacteria are highly social organisms that interact, and it is these interactions that have been proposed to be critical for establishing spatially structured communities. A primary means by which bacteria interact is via small, diffusible molecules including dedicated signals and metabolic by-products; however, quantitatively monitoring the production of these molecules in time and space with the micron-scale resolution required has been challenging. In this perspective, scanning electrochemical microscopy (SECM) is discussed as a powerful tool to study microbe–microbe interactions through the detection of small redox-active molecules. We highlight SECM as a means to quantify and spatially resolve the chemical mediators of bacterial interactions and begin to elucidate the mechanisms used by bacteria to regulate the emergent properties of biofilms.


2015 ◽  
Vol 15 (3) ◽  
pp. 205-214 ◽  
Author(s):  
Ariane Roseblade ◽  
Frederick Luk ◽  
Alison Ung ◽  
Mary Bebawy

Author(s):  
Carmen Andrade ◽  
Ana Martínez-Serrano ◽  
Miguel Ángel Sanjuán ◽  
José Antonio Tenorio Ríos

Clinker production is being reduced worldwide in response to the need to drastically lower greenhouse gas emissions. The trend began in the nineteen seventies with the advent of mineral additions to replace clinker. Blast furnace slag and fly ash, industrial by-products that were being stockpiled in waste heaps at the time, have not commonly been included in cements. Supply of these additions is no longer guaranteed, however, due to restrained activity in the source industries for the same reasons as in clinker production. The search is consequently on for other additions that may lower pollutant gas emissions without altering cement performance. In this research bentonite, a very common clay, was used as such an addition directly, with no need for pre-calcination, an still novel approach that has gone little explored to date for reinforced concrete with structural applications. The results of the mechanical strength and chemical resistance (to sulfates, carbonation and chlorides) tests conducted are promising. The carbonation findings proved to be of particular interest, for that is the area where cement with mineral additions tend to be least effective. In the bentonite-bearing material analysed here, however, carbonation resistance was found to be low as or lower than observed in plain Portland cement.


Author(s):  
Anna Raguzzini ◽  
Elisabetta Toti ◽  
Marco Bernardi ◽  
Fabio Castellucci ◽  
Valentina Cavedon ◽  
...  

Background:: Interleukin (IL)-6, total antioxidant capacity (TAC) and uric acid (UA) increase after exercise in able-bodied individuals. Wheelchair Basketball Athletes (WBA), having low muscle mass, could be at risk of post-exercise ketosis. Objective:: This study aimed to evaluate the post-exercise ketosis, IL-6 and antioxidant response, in WBA of the Italian National team, after a simulated match. Methods:: Dietary intakes, Starvation Symptoms Inventory (SSI), percentage of fat mass (FM%) and basal Respiratory Exchange Ratio (RER) and Basal Energy Expenditure (BEE), were evaluated. Salivary TAC, UA and IL-6 were measured: before (PreM), at the end (EM) and 20 minutes after (PostM) the match. Capillary glucose and β-hydroxybutyrate (βHB) were monitored. Percentage of Heart Rate Reserve (%HRR) was measured to evaluate exercise intensity. Results:: WBA had low carbohydrates (43.5% of daily energy intake (En)) and high fat (36.3% En) intakes. The increase in UA at PostM correlated with En (0.810, p<0.01) and was inversely related to βHB at EM (-0.719, p<0.05). Furthermore, at PostM growing IL-6 levels correlated with BEE (0.778, p<0.05) and inversely related to FM% (-0.762, p<0.5) were found, which in turn was correlated to SSI (0.781, p<0.05). Also βHB PostM correlated with SSI (0.761, p<0.05) but was inversely related to RER (-0.745, p<.05) and En (-0.826, p<0.01). Conclusions:: Our study suggests that some WBA should improve their dietary habit in order to prevent post-exercise ketosis and ameliorate the endogenous antioxidant response after exercise.


Author(s):  
Karen Y. Reyes-Melo ◽  
Adrián A. Galván-Rodrigo ◽  
Isaí E. Martínez-Olivo ◽  
Guillermo Núñez-Mojica ◽  
Francisco G. Ávalos-Alanís ◽  
...  

Background: Larrea tridentata is a dominant shrub in the deserts of North America and is recognized for its various traditional uses. More than 50 traditional uses have been recorded. Regarding its chemical composition, the products of the mevalonate, shikimate, and malonate pathways are predominant. L. tridentata has nordihydroguaiaretic acid (NDGA), one of its most studied secondary metabolites that exhibited remarkable different biological activities: sequestration of reactive oxygen species, inhibition of lipoxygenases (LOX) and activation of the endogenous antioxidant response mediated by nuclear factor erythroid 2–related factor 2 (NRF2). Objective and Methods: This review seeks to draw attention to metabolites other than NDGA and which also contribute to the various biological activities of L. tridentata. Therefore, the present review includes those reports focused on the pharmacological properties of the organic extracts of L. tridentata and its natural products with promising values. Results and Conclusion: Among the most promising and widely reported metabolites from L. tridentata, are: 3’-demethoxy-6-O-demethylisoguaiacin, 3’-O-methylnordihydroguiaretic acid, meso-dihydroguaiaretic acid, and tetra-O-methylnorhydroguiaretic acid. These have been reported to exhibit antibacterial, antiprotozoal, anthelmintic, antifungal, antiviral, anticancer, and antioxidant activities.


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