Insights into the Relation between Oxidative Stress and Malaria: A Mechanistic and Therapeutic Approach

The mortality rate due to malaria has increased tremendously in the last decade. Even though the causative agent of this disease is known, the preventive measures are not potent enough to control the spread of this disease. Malarial infection involves a strong interrelationship between oxidative stress and pathogenesis. This review addresses the various oxidative stress-related mechanisms associated with vector defense, host immunity, plasmodial pathogenesis, and corresponding therapeutic strategies. The mechanisms involving host and vector defense show both similarity and contradiction to the processes involving plasmodial pathogenesis under different circumstances. Therefore, corresponding ameliorative peculiarities are observed in the therapeutic mechanisms adopted by the anti-malarial drugs. The malarial parasite augments oxidative stress to weaken the host and exerts antioxidant effects against host defense mechanisms. However, the anti-malarial drugs induce oxidative insult to reduce parasitic load and exert antioxidant effects against parasite infection-induced oxidative stress in host. Thus, the anti-malarial drugs exhibit antioxidant activity in hosts and/or pro-oxidant activity in parasites.

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Extensive Thiol Profiling for Assessment of Intracellular Redox Status in Cultured Cells by HPLC-MS/MS

Antioxidants ◽

10.3390/antiox11010024 ◽

2021 ◽

Vol 11 (1) ◽

pp. 24

Author(s):

Jiandong Wu ◽

Anna Chernatynskaya ◽

Annalise Pfaff ◽

Huari Kou ◽

Nan Cen ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Responses ◽

Defense Mechanisms ◽

High Performance ◽

Cultured Cells ◽

Redox Status ◽

Oxidative Stress Responses ◽

Sulfur Containing ◽

And Oxidative Stress ◽

Oxidative Insult

Oxidative stress may contribute to the pathology of many diseases, and endogenous thiols, especially glutathione (GSH) and its metabolites, play essential roles in the maintenance of normal redox status. Understanding how these metabolites change in response to oxidative insult can provide key insights into potential methods of prevention and treatment. Most existing methodologies focus only on the GSH/GSH disulfide (GSSG) redox couple, but GSH regulation is highly complex and depends on several pathways with multiple redox-active sulfur-containing species. In order to more fully characterize thiol redox status in response to oxidative insult, a high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method was developed to simultaneously determine seven sulfur-containing metabolites, generating a panel that systematically examines several pathways involved in thiol metabolism and oxidative stress responses. The sensitivity (LOQ as low as 0.01 ng/mL), accuracy (88–126% spike recovery), and precision (≤12% RSD) were comparable or superior to those of existing methods. Additionally, the method was used to compare the baseline thiol profiles and oxidative stress responses of cell lines derived from different tissues. The results revealed a previously unreported response to oxidative stress in lens epithelial (B3) cells, which may be exploited as a new therapeutic target for oxidative-stress-related ocular diseases. Further application of this method may uncover new pathways involved in oxidative-stress-related diseases and endogenous defense mechanisms.

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Malarial parasites and antioxidant nutrients

Parasitology ◽

10.1017/s0031182000075533 ◽

1993 ◽

Vol 107 (S1) ◽

pp. S95-S106 ◽

Cited By ~ 28

Author(s):

O. A. Levander ◽

A. L. Ager

Keyword(s):

Oxidative Stress ◽

Fatty Acids ◽

Unsaturated Fatty Acids ◽

Malarial Parasite ◽

Vitamin E Deficiency ◽

Highly Unsaturated Fatty Acids ◽

Malarial Infection ◽

Rapid Induction ◽

Oxidative Stress Status ◽

The Status

SUMMARYSusceptibility to oxidative stress is a well-established feature of the malarial parasite. Pharmacologists have taken advantage of this property to design highly effective pro-oxidant antimalarial drugs. Less well appreciated is the fact that nutritional manipulation of host oxidative stress status by dietary means can have a profound effect on the growth of the parasite. In particular, rapid induction of vitamin E deficiency in mice by feeding highly unsaturated fatty acids (fish oil) strongly suppresses plasmodial growth. Likewise, the status of other antioxidant nutrients (e.g., riboflavin or vitamin C) may also influence the course of malarial infection under certain conditions. A combined nutritional pharmacology approach may offer some promise in controlling malaria.

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Crosstalk between Long-Term Sublethal Oxidative Stress and Detrimental Inflammation as Potential Drivers for Age-Related Retinal Degeneration

Antioxidants ◽

10.3390/antiox10010025 ◽

2020 ◽

Vol 10 (1) ◽

pp. 25

Author(s):

Lara Macchioni ◽

Davide Chiasserini ◽

Letizia Mezzasoma ◽

Magdalena Davidescu ◽

Pier Luigi Orvietani ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Mechanisms ◽

Age Related Macular Degeneration ◽

Inflammasome Activation ◽

Related Factor ◽

Nuclear Factor ◽

Rpe Cells ◽

Age Related ◽

Oxidative Insult

Age-related retinal degenerations, including age-related macular degeneration (AMD), are caused by the loss of retinal pigmented epithelial (RPE) cells and photoreceptors. The pathogenesis of AMD, deeply linked to the aging process, also involves oxidative stress and inflammatory responses. However, the molecular mechanisms contributing to the shift from healthy aging to AMD are still poorly understood. Since RPE cells in the retina are chronically exposed to a pro-oxidant microenvironment throughout life, we simulated in vivo conditions by growing ARPE-19 cells in the presence of 10 μM H2O2 for several passages. This long-term oxidative insult induced senescence in ARPE-19 cells without affecting cell proliferation. Global proteomic analysis revealed a dysregulated expression in proteins involved in antioxidant response, mitochondrial homeostasis, and extracellular matrix organization. The analyses of mitochondrial functionality showed increased mitochondrial biogenesis and ATP generation and improved response to oxidative stress. The latter, however, was linked to nuclear factor-κB (NF-κB) rather than nuclear factor erythroid 2–related factor 2 (Nrf2) activation. NF-κB hyperactivation also resulted in increased pro-inflammatory cytokines expression and inflammasome activation. Moreover, in response to additional pro-inflammatory insults, senescent ARPE-19 cells underwent an exaggerated inflammatory reaction. Our results indicate senescence as an important link between chronic oxidative insult and detrimental chronic inflammation, with possible future repercussions for therapeutic interventions.

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Phytochemical Analysis of Anti-Inflammatory and Antioxidant Effects of Mahonia aquifolium Flower and Fruit Extracts

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/2879793 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 13

Author(s):

Andra-Diana Andreicut ◽

Alina Elena Pârvu ◽

Augustin Cătălin Mot ◽

Marcel Pârvu ◽

Eva Fischer Fodor ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Activity ◽

Stress Index ◽

Tnf Alpha ◽

Phytochemical Analysis ◽

Anti Inflammatory ◽

Mahonia Aquifolium ◽

Antioxidant Effects

Oxidative stress and inflammation are interlinked processes. The aim of the study was to perform a phytochemical analysis and to evaluate the antioxidant and anti-inflammatory activities of ethanolic Mahonia aquifolium flower (MF), green fruit (MGF), and ripe fruit (MRF) extracts. Plant extract chemical composition was evaluated by HLPC. A DPPH test was used for the in vitro antioxidant activity. The in vivo antioxidant effects and the anti-inflammatory potential were tested on a rat turpentine oil-induced inflammation, by measuring serum nitric oxide (NOx) and TNF-alpha, total oxidative status (TOS), total antioxidant reactivity (TAR), oxidative stress index (OSI), 3-nitrothyrosine (3NT), malondialdehyde (MDA), and total thiols (SH). Extracts were administrated orally in three dilutions (100%, 50%, and 25%) for seven days prior to inflammation. The effects were compared to diclofenac. The HPLC polyphenol and alkaloid analysis revealed chlorogenic acid as the most abundant compound. All extracts had a good in vitro antioxidant activity, decreased NOx, TOS, and 3NT, and increased SH. TNF-alpha was reduced, and TAR increased only by MF and MGF. MDA was not influenced. Our findings suggest that M. aquifolium has anti-inflammatory and antioxidant effects that support the use in primary prevention of the inflammatory processes.

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Pathomechanisms of Oxidative Stress in Inflammatory Bowel Disease and Potential Antioxidant Therapies

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/4535194 ◽

2017 ◽

Vol 2017 ◽

pp. 1-18 ◽

Cited By ~ 96

Author(s):

Tian Tian ◽

Ziling Wang ◽

Jinhua Zhang

Keyword(s):

Oxidative Stress ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Defense Mechanisms ◽

Gastrointestinal Disease ◽

Mucosal Immune Response ◽

Stress Signaling ◽

Substantial Progress ◽

Inflammatory Bowel ◽

Underlying Mechanisms

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disease whose incidence has risen worldwide in recent years. Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of IBD. This review highlights the generation of reactive oxygen species (ROS) and antioxidant defense mechanisms in the gastrointestinal (GI) tract, the involvement of oxidative stress signaling in the initiation and progression of IBD and its relationships with genetic susceptibility and the mucosal immune response. In addition, potential therapeutic strategies for IBD that target oxidative stress signaling are reviewed and discussed. Though substantial progress has been made in understanding the role of oxidative stress in IBD in humans and experimental animals, the underlying mechanisms are still not well defined. Thus, further studies are needed to validate how oxidative stress signaling is involved in and contributes to the development of IBD.

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Coordination of frontline defense mechanisms under severe oxidative stress

Molecular Systems Biology ◽

10.1038/msb.2010.50 ◽

2010 ◽

Vol 6 (1) ◽

pp. 393 ◽

Cited By ~ 44

Author(s):

Amardeep Kaur ◽

Phu T Van ◽

Courtney R Busch ◽

Courtney K Robinson ◽

Min Pan ◽

...

Keyword(s):

Oxidative Stress ◽

Defense Mechanisms

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Protein carbonyl group content in patients affected by familiar chronic nail candidiasis

Mediators of Inflammation ◽

10.1080/09629350310001599693 ◽

2003 ◽

Vol 12 (4) ◽

pp. 247-249 ◽

Cited By ~ 2

Author(s):

S. Gangemi ◽

A. Saija ◽

A. Tomaino ◽

F. Cimino ◽

R. A. Merendino ◽

...

Keyword(s):

Oxidative Stress ◽

Defense Mechanisms ◽

Protein Carbonyl ◽

Intercellular Adhesion Molecule ◽

Carbonyl Groups ◽

Intercellular Adhesion Molecule 1 ◽

Protein Carbonyl Groups ◽

Halide System ◽

Reactive Nitrogen Intermediates ◽

Hands And Feet

Familiar chronic nail candidiasis (FCNC) is a rare disorder characterized by early-onset infections caused by different species of Candida, restricted to the nail of the hands and feet, and associated with a low serum concentration of intercellular adhesion molecule 1. Host defense mechanisms against candidiasis require the cooperation of many immune cells through several candidacidal mechanisms, including oxygen-dependent killing mechanisms, mediated by a superoxide anion radical myeloperoxidase-H2O2-halide system, and reactive nitrogen intermediates. We analyzed protein carbonyl groups (considered a useful marker of oxidative stress) in the serum of patients belonging to a five-generation Italian family with an isolated form of FCNC.Serum protein carbonyl groups in FCNC patients were significantly lower than those measured in healthy donors.Also, if this hypothesis is merely speculative, we could suggest that the decreased circulating level of protein carbonyl groups in these patients is not a marker of a lower oxidative stress condition, but might be linked to a lower protease activity.

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MALARIAL PIGMENT (HEMATIN) AS A FACTOR IN THE PRODUCTION OF THE MALARIAL PAROXYSM

Journal of Experimental Medicine ◽

10.1084/jem.15.6.579 ◽

1912 ◽

Vol 15 (6) ◽

pp. 579-597 ◽

Cited By ~ 19

Author(s):

Wade H. Brown

Keyword(s):

Human Subject ◽

Toxic Substance ◽

Malarial Parasite ◽

Striking Similarity ◽

Conservative Estimate ◽

Experimental Conditions ◽

Malarial Infection ◽

Sequence Of Events ◽

Abundant Evidence ◽

The One

The paroxysm of hematin intoxication in the rabbit undoubtedly presents many features of striking similarity to the paroxysm of human malaria; still one must hesitate to apply such results unreservedly in an attempt to identify the causative agent of the malarial paroxysm. When, in addition to the character of the paroxysm, we consider the sequence of events in the two instances, the analogy becomes so close that it seems impossible to regard the matter as a mere coincidence. The injection of hematin, especially in fractional doses, is in a measure comparable to the liberation of hematin into the human circulation by the malarial parasite. In these experiments, See PDF for Structure both solution and finely divided suspensions of hematin have been found equally effective in eliciting the phenomena of the paroxysm, and while it seems possible that a portion of the malarial pigment might be dissolved in the alkaline human serum, such an assumption is probably not essential. It might be objected that the toxic action of foreign hematin thus injected into the circulation would probably be greater than that of hematin derived from an animal's own blood, but as far as I have been able to determine, this objection does not seem valid, as rabbit hematin, dog hematin, and ox hematin produce in the rabbit effects that are alike in both character and degree. The dose of hematin remains as the one factor to which it is possible to attach some degree of uncertainty, but even here the author feels that the range of experimental conditions has been kept within the bounds of legitimate analogy with conditions existing in the human subject of malarial infection. Finally, the most conservative estimate of the value of such experiments points strongly to the fact that we have at least a potentially toxic substance in the pigment hematin as liberated by the malarial parasite into the circulation of the human host. There is also abundant evidence to show that the action of hematin is not confined to the paroxysmal phenomena of malaria, but that other features of the disease may find their explanation in the action of this pigment. For the present, however, it seems advisable to confine the discussion to this one phase of the question.

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Macrophage Autophagy and Oxidative Stress: An Ultrastructural and Immunoelectron Microscopical Study

Oxidative Medicine and Cellular Longevity ◽

10.1155/2011/282739 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 12

Author(s):

Ida Perrotta ◽

Valentina Carito ◽

Emilio Russo ◽

Sandro Tripepi ◽

Saveria Aquila ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Programmed Cell Death ◽

Defense Mechanisms ◽

Ultrastructural Localization ◽

Microscopical Study ◽

Beclin 1 ◽

Cell Organelles ◽

A Cell ◽

First Time

The word autophagy broadly refers to the cellular catabolic processes that lead to the removal of damaged cytosolic proteins or cell organelles through lysosomes. Although autophagy is often observed during programmed cell death, it may also serve as a cell survival mechanism. Accumulation of reactive oxygen species within tissues and cells induces various defense mechanisms or programmed cell death. It has been shown that, besides inducing apoptosis, oxidative stress can also induce autophagy. To date, however, the regulation of autophagy in response to oxidative stress remains largely elusive and poorly understood. Therefore, the present study was designed to examine the ratio between oxidative stress and autophagy in macrophages after oxidant exposure (AAPH) and to investigate the ultrastructural localization of beclin-1, a protein essential for autophagy, under basal and stressful conditions. Our data provide evidence that oxidative stress induces autophagy in macrophages. We demonstrate, for the first time by immunoelectron microscopy, the subcellular localization of beclin-1 in autophagic cells.

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