Many pathologic disease can be considered as related to an Endogenous toxicological moves and in time dependent way (kinetics and dynamic of the process). In this work starting from the analysis of relevant literature involved with different disease and related to the endogenous local micro- environment some global conclusion useful as new tools for innovative pharmacological strategies will be submitted to the researcher. Physiology, pathology concept linked to the endogenous toxicological local micro-environment status as new research instruments. The same carcinogenesis process can be related also to endogenous agents that may have a major contribution in spontaneously process. (Reactive oxygen species (ROS), which are involved in multiple cellular processes by physiologically transporting signal as a second messenger or pathologically oxidizing DNA, lipids, and proteins).
Understanding the obesity-related genes may provide future therapeutic strategies to modulate disease progression. UCP2 separates oxidative phosphorylation (OXPHOS) from ATP production in the inner mitochondria. Figure 1 shows the differences among UCP1, 2, 3. The main role of UCP2 is controlling the metabolism of energy in the cells [1-3]. Besides that, the expression of UCP2 is associated with chronic inflammation due to reactive oxygen species (ROS). In this regard, in injured cells and tissues, ROS could be decreased by reducing the proton motor force by the anti-inflammatory effect of UCP2 [4].
Blood plays an important role in oxygen absorption and its transfer to organs and tissues in vertebrates, as well as in a number of invertebrate species. Numerous interactions between cellular and non-cellular blood components constantly occur. A special role in these interactions belongs to erythrocytes and leukocytes, between which oxygen is constantly exchanged and activated, which we showed directly in whole blood. Blood is a liquid tissue, which is a complex cooperative system and has many inherent functions and the most important one is the ability to maintain the homeostasis of the body. Our experience has shown that despite its high optical density, undiluted blood of humans and animals can be a source of radiation due to the transformation of the energy of electron-excited (EEE) states and secondary processes occurring in the whole blood system. Parameters of this radiation - ultra-weak photons emission (UWPE) from blood - depend upon its physiological properties and reflect the physiological state of a donor. Analysis of UWPE from non-diluted blood is a simple and sensitive method that allows to monitor the course of treatment of a patient. In spite of high opacity of non-diluted blood it may be a strong source of UWPE both in the presence and absence of UWPE enhancers. Analysis of patterns of UWPE from blood reveals its highly non-linear, stable non-equilibrium and cooperative properties. Characteristic of a living system.
Graphical abstract
Biodegradation of implanted gold in human tissue. TEM images reveal markedly biodegradation of implanted gold and re-crystallization of dissolved gold as nanoparticle of different size, shape and crystallinity. Highly crystalline icosahedral Au nanoparticle and the corresponding power spectrum are shown on top.
Background: Despite the importance of biodegradation for the durability of metal prosthesis and the widely use of gold implants, there exist a lack of knowledge regarding the stability of pure gold in tissue.
Methods: We studied biodegradation of grids of pure gold, nickel, and copper as well as middle ear prosthesis of gold, platinum or titanium. Metals were implanted into rat skin and humans. Dissolution and re-crystallization process of the metals was analysed using SEM, TEM, power spectra as well as elemental analysis by EDX and EELS/ESI.
Results: Biodegradation of gold was detected, presumably by solving and re-precipitation of gold around implants. Gold cluster, nanoparticles, and mesostructures were detected, formed by dissolution and re-crystallization process. This process results into a migration of gold into the farer off tissue. Cellular filaments as biomolecular templates facilitate the formation of mesostructures. Loss of function of middle ear prosthesis by biodegradation is caused by chronic inflammation and fibrosis. Indeed, similar processes were detected with platinum, but in a very lower level.
Conclusion: Noble metal implants undergo biodegradation in oxidative environment in tissue. The dissolution – recrystallization process can be explained by enzyme catalysed redox processes comprising reactive oxygen species and reduction agents as ascorbic acid present in cells and body tissue. Enymes like myeloperoxidase inside lysosomes of inflammatory cells produce hypochloride ions and H2O2 which can dissolve the gold.
General significance: The crucial role of the specific chemical environments of gold implants in tissue for their chemical stability and durability of function has been demonstrated. Due to widely use and importance of gold implants, this finding is of general interes.
The biological changes caused by oxidative stress (OS) are known to be involved in the etiology of neurodegenerative disorders, including Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and Parkinson’s disease. The brain is particularly vulnerable to OS due to its high lipid content and extensive consumption of oxygen. OS processes, particularly the excessive production of reactive oxygen species (ROS), play a critical role in how neurodegenerative disorders develop. This is evidenced by in vivo studies investigating various biomolecules related to OS, such as products of lipid and DNA oxidation. Accordingly, ROS can also cause oxidative-related damage in neurodegenerative disorders, including dopamine auto-oxidation, mitochondrial dysfunction, glial cell activation, α-synuclein aggregation, excessive free iron, and changes in calcium signaling. Furthermore, excessive levels of cellular oxidants reduce antioxidant defenses, which in turn propagate the cycle of OS. As such, it is increasingly important to determine the linkage between a high intake of antioxidants through dietary interventions and a lower risk of developing neurodegenerative diseases. Indeed, in addition to modulating the immune system, optimal nutritional status is capable of changing various processes of neuroinflammation known to be involved in the pathogenesis of neurodegeneration. Accordingly, a better understanding of the role ROS plays in the etiology of neurodegeneration is needed, along with the identification of dietary interventions that may lead to improved therapeutic strategies for both the treatment and prevention of neurodegenerative disorders. Therefore, this review presents a comprehensive summary of the role of ROS in the pathogenesis of neurodegenerative disorders. In addition, nutrients believed to be useful for mitigating and counteracting ROS are discussed.
Protein phosphorylation regulates several dimensions of cell fate and is substantially dysregulated in pathophysiological instances as evident spatiotemporally via intracellular localizations or compartmentalizations with discrete control by specific kinases and phosphatases. Cardiovascular disease manifests as an intricately complex entity presenting as a derangement of the cardiovascular system. Cardiac or heart failure connotes the pathophysiological state in which deficient cardiac output compromises the body burden and requirements. Protein kinases regulate several pathophysiological processes and are emerging targets for drug lead or discovery. The protein kinases are family members of the serine/threonine phosphatases. Protein kinases covalently modify proteins by attaching phosphate groups from ATP to residues of serine, threonine and/or tyrosine. Protein kinases and phosphatases are pivotal in the regulatory mechanisms in the reversible phosphorylation of diverse effectors whereby discrete signaling molecules regulate cardiac excitation and contraction. Protein phosphorylation is critical for the sustenance of cardiac functionalities. The two major contributory ingredients to progressive myocardium derangement are dysregulation of Ca2+ processes and contemporaneous elevated concentrations of reactive oxygen species, ROS. Certain cardiac abnormalities include cardiac myopathy or hypertrophy due to response in untoward haemodynamic demand with concomitant progressive heart failure. The homeostasis or equilibrium between protein kinases and phosphatases influence cardiac morphology and excitability during pathological and physiological processes of the cardiovascular system. Inasmuch as protein kinases regulate numerous dimensions of normal cellular functions, the pathophysiological dysfunctionality of protein kinase signaling pathways undergirds the molecular aspects of several cardiovascular diseases or disorders as related in this study. These have presented protein kinases as essential and potential targets for drug discovery and heart disease therapy.
The commonest etiology of acute kidney injury (AKI) is Sepsis that results in an escalation of morbidity and mortality in the hospital intensive care units. Existentially, the therapy of septic AKI rather than being definitive or curative is just supportive, without tackling the pathophysiology. Usually, Sepsis gets correlated with systemic inflammation, along with the escalated generation of Reactive oxygen species (ROS), in particular superoxide. Simultaneously liberation of nitric oxide (NO) subsequently reacts with the superoxide, thus, resulting in the generation of reactive nitrogen species (RNS), that is mostly peroxynitrite. This sepsis stimulated generation of ROS in addition to RNS might cause a reduction in the bioavailability of NO that modulates microcirculation aberrations, localized tissue hypoxia as well as mitochondrial impairment, thus starting a vicious cycle of cellular damage which results in AKI. Here we conducted a systematic review utilizing search engine PubMed, Google scholar; Web of science; Embase; Cochrane review library utilizing the MeSH terms like septic AKI; ROS; inducible nitric oxide synthase (iNOS); nicotinamide adenine nucleotide phosphate(NADPH)oxidase complex; Oxidative stress; Renal medullary hypoxia; Hypoxia inducible factor1; hypoxia responsive enhancer A; mitochondrial impairment; Intrarenal oxygenation; urinary oxygenation; erythropoietin gene; RRT; NAC; Vitamin C from 1950 to 2021 till date. We found a total of 6500 articles out of which we selected 110 articles for this review. No meta-analysis was done. Thus here we detail the different sources of ROS, at the tie of sepsis, besides their pathophysiological crosstalk with the immune system, microcirculation as well as mitochondria that can result in the generation of AKI. Furthermore, we detail the therapeutic utility of N-acetylcysteine (NAC), besides the reasons for its success in ovine as well as porcine models of AKI. Moreover, we discuss preclinical along with clinical for evaluation of Vitamin C’s antioxidant effects as well as pleiotropic effects as a stress hormone that might aid in abrogation of septic AKI.
Neurological disorders are a significant cause of mortality and disability across the world. The current aging population and population expansion have seen an increase in the prevalence of neurological and psychiatric disorders such as anxiety, bipolar disorder, depression, epilepsy, multiple sclerosis and schizophrenia. These pose a significant societal burden, especially in low - and middle-income countries. Many neurological disorders have complex mechanisms and lack definitive cures; thus, improving our understanding of them is essential. The pathophysiology of neurological disorders often includes inflammation, mitochondrial dysfunction and oxidative stress. Oxidative stress processes, especially the generation of reactive oxygen species, are key mechanisms in the development of neurological disorders. Oxidative stress refers to an imbalance between the production of reactive oxygen species and antioxidants that can counteract them. Through their impacts on the pathophysiology of neurological disorders, nutrients with anti-inflammatory, neuroprotective and antioxidative properties have been suggested to prevent or mitigate these disorders. Certain vitamins, minerals, polyphenols and flavonoids may have therapeutic effects as adjuvant treatments for neurological disorders. Diet quality is also a risk factor for some neurological and psychiatric disorders and addressing nutritional deficiencies may alleviate symptoms. Therefore, optimizing nutritional intake may represent a potential treatment or prevention strategy. This review summarizes a selection of promising nutrients for the prevention and amelioration of neurological disorders to provide a summary for scientists, clinicians and patients, which may improve understanding of the potential benefits of nutrients in the treatment of neurological disorders.
Elif Tan*, Ebru Gezgincioğlu and Özlem Gülmez and Özlem Barış
Published on: 22nd September, 2023
This study aimed to determine whether the essential oils of thyme, ginger, and mint from medicinal aromatic plants can provide resistance to the pathogen Fusarium oxysporum in the maize plant. To this end, the antifungal effect of 0.1 ml, 0.25 ml, 0.5 ml, and 1 ml essential oil amounts was determined by the agar disc diffusion method. It was determined that concentrations containing 0.1, and 0.25 ml essential oil showed no antifungal effects, however, concentrations containing 0.5 and 1 ml essential oil had antifungal effects. The most effective concentration was found to be 1 ml of essential oil in all three species. The maize was grown under hydroponic conditions. Thyme, ginger, and mint essential oils (1 g/100 ml) were applied to the root medium of the grown maize plant on the 8th day. An F. oxysporum suspension containing 107 spores was applied after 24 hours and harvested 3 days later. When the reactive oxygen species (H2O2) and MDA amounts of the harvested plants were examined, it was observed that there was an increase in the population of F. oxysporum. However, applications of thyme, ginger, and mint essential oil have been observed to significantly reduce these. It was also determined that essential oils protected the plant against F. oxysporum by increasing antioxidant enzyme activities. Although these three essential oils applied have antifungal properties, it has been observed that the best effect belongs to thyme essential oil. The results show that essential oils of thyme ginger and mint can be used as potential fungicides against the pathogen F. oxysporum in maize cultivation
Ana Carolina Agüero Aguilera, María Eugenia Mónaco, Sandra Lazarte, Emilse Ledesma Achem, Natalia Sofía Álvarez Asensio, Magdalena María Terán, Blanca Alicia Issé, Marcela Medina and Cecilia Haro*
Published on: 29th April, 2024
Background: Acute leukemia is the result of clonal transformation and proliferation of a hematopoietic progenitor giving rise to poorly differentiated neoplastic cells. Reactive oxygen species play a role in maintaining the quiescence, self-renewal, and long-term survival of hematopoietic stem cells, but it is unclear how they would affect disease onset and progression. The aim is to evaluate, at the transcriptional and systemic level, the oxidative-inflammatory status in newly diagnosis acute leukemia patients. Methods: Seventy acute leukemia patients [26 acute lymphoblastic leukemia (ALL), 13 Acute Promyelocytic Leukemia (APL), and 31 Acute Myeloid Leukemia (AML)] and forty-one healthy controls were analyzed. Malondialdehyde and catalase activity were evaluated. Gene expression of NRF2, SOD, PRDX2, CAT, IL-6, and TNF-α was analyzed by real-time PCR.Results: Malondialdehyde concentration was similar in all groups studied. Catalase activity was significantly higher in AML and APL patients compared to controls, while ALL showed similar activity to the healthy group. NRF2, CAT, and PRDX2 expression levels were similar between groups, SOD expression was downregulated in all acute leukemia patients. TNF-α expression was lower in AML groups than in healthy individuals, and IL-6 mRNA expression was downregulated in ALL and APL.Conclusion: This is the first report that correlates transcriptional and systemic parameters associated with the oxidative inflammatory status in newly diagnosed acute leukemia. Some of the parameters evaluated could be used as biomarkers in the selection of an effective therapeutic strategy and will open new directions for the follow-up and evolution of this disease.
Ibrahima Sory Sow*, Naïma El Manssouri and Dong Yang
Published on: 15th May, 2024
The N-hydroxydodecanamide (HA12) and its complexes tri-hydroxamato-iron(III) and di-hydroxamto-iron(III) chloride (HA8Fe3 and HA12Fe3Cl, respectively) showed antibacterial and antimycobacterial activities. The proteomic analysis demonstrated that the targets of Hydroxamic Acid (HA) and their complexes were involved in the biosynthesis of mycobacterial cell walls. The Reactive Oxygen Species (ROS) is one of the key elements to cause oxidative stress, damaging DNA, and cell membranes impaired during the procedure to kill bacteria. Here, the ROS production was determined to evaluate the compounds HA12, HA8Fe3, HA12Fe3Cl, and ZnCl2 against bacteria using 2’,7’-dichlorofluorescein diacetate (DCFDA) by spectrofluorometric analysis. The low fluorescence was observed using the compounds HA12, HA8Fe3, HA12Fe3Cl, and ZnCl2 treating the S. aureus and E. coli, indicating that the ROS production could not be observed using the compounds used at a dose higher than the Minimum Inhibitory Concentration (MIC). It was noted that the ROS determination could be performed with a concentration less than or equal to the MIC. This would enable the mechanism of action linked to the ROS production by HA and their metal complexes to be determined.
Saleh Alkarri*, Melinda Frame, John Cairney, Lee Maddan, Jin H Kim and Jonathan O Rayner
Published on: 29th May, 2024
Robust anti-microbial surfaces that are non-toxic to users have widespread application in medical, industrial, and domestic arenas. Magnesium hydroxide has recently gained attention as an anti-microbial compound that is non-toxic, biocompatible, and environmentally friendly. Here we demonstrate melt compound and thermally embossed methods for coating polypropylene with Mg(OH)2 nanoplatelets and copper-infused Mg(OH)2 nanoplatelets. Polypropylene articles coated with Mg(OH)2 nanoplatelets and copper-infused Mg(OH)2 nanoplatelets exhibit a log 8 kill of E.coli within 24 hours. In addition, Mg(OH)2 NPs suspension, at 0.25% reduced SARSCoV-2 virus titers in the solution by 2.5 x 103 PFU/mL or 29.4%, while the Cu-infused Mg(OH)2 NPs suspension, at 0.25% reduced titers by 8.1 x 103 PFU/mL or 95.3%. Fluorescence microscopy revealed that reactive oxygen species (ROS) are produced in bacteria in response to Mg(OH)2 and Cu-infused Mg(OH)2 nanoplatelets which appears to be an important but not the sole mode of anti-microbial action of the nanoplatelets. Plastics with anti-microbial surfaces from where biocides are non-leachable are highly desirable. This work provides a general fabrication strategy for developing anti-microbial plastic surfaces.
Spin-depending internal magnetic interactions in oxygen are crucial for the chemistry and photobiology of this molecule. Photosynthesis, respiration, and many other life-supporting oxygen reactions are governed by enzymes that use fine magnetic forces to overcome the spin-forbidden character of all aerobic metabolism. Life on Earth occurs on the border between combustion and oxidative phosphorylation, and this balance is largely dependent on reactive oxygen species. ROS can cause apoptosis or cell necrosis, and ROS also controls homeostasis through numerous signaling functions. Until recently, biochemists had not paid attention to internal magnetic interactions that influence the chemical activity of such ROS as superoxide ion, singlet oxygen, peroxynitrite, and many others. The role of superoxide dismutase, the oldest enzyme on the Earth, which provides superoxide concentration control, stresses the importance of the O2-• species as the precursor of many other ROS. Spin-orbit coupling in O2-• and O2 species are the main internal magnetic interactions that could influence cancer growth and be connected with cancer therapy.
Arturo Solís Herrera*, María del Carmen Arias Esparza and Sergey Suchkov
Published on: 31st January, 2025
Antioxidants are groups of compounds that neutralize free radicals and Reactive Oxygen Species (ROS) in the cell [1]. Antioxidant activity in food and beverages has become one of the most interesting features in the science community. These antioxidants provide protection against damage caused by free radicals played important roles in the development of many chronic diseases including cardiovascular diseases, aging, heart disease, anemia, cancer, and inflammation [2].
Mitochondria are essential intracellular organelles that significantly influence various cellular processes, including metabolism, stress response, and cell fate. Their precise regulation is crucial for maintaining both organelle and cellular homeostasis. Wound healing is a complex, multifactorial process that relies on the coordinated actions of multiple cell types and numerous cellular mechanisms. Dysregulation in this process can lead to chronic wounds, which pose substantial challenges for healthcare systems and present limited treatment options due to their intricate pathogenesis. Recent research has increasingly focused on the role of mitochondria in wound healing, revealing their involvement in critical processes such as metabolism, apoptosis, and redox signaling. Mitochondrial dynamics play a vital role in wound healing by adapting to cellular demands and environmental cues. Moreover, mitophagy, the selective degradation of damaged mitochondria, is crucial for maintaining mitochondrial integrity and function during the healing process. Mitochondria are not only pivotal in energy production but also in calcium homeostasis and the generation of mitochondrial reactive oxygen species, which are essential for signaling during wound repair. As wound healing progresses through distinct yet overlapping stages mitochondria facilitate the energy demands of repair and contribute to cytoskeletal remodeling necessary for wound closure. Understanding the multifaceted roles of mitochondria in wound healing could lead to novel therapeutic approaches for chronic wounds. Future research should prioritize investigating mitochondrial dynamics and functions in human tissues to develop targeted strategies for enhancing wound healing outcomes.
A specialized installation has been developed for microscopic study of the Reactive Oxygen Species (ROS) formation during microwave irradiation of biological samples with automated control / mechanized tube and real-time data acquisition. The above installation can be used in biomedical practice for: standardization or certification of the microwave sources; testing of the potential antioxidants that protect tissues from ROS-induced effects; testing fluorescent sensors for ROS; analysis of ROS localization and distribution in various tissues in order to establish specific pharmaco-physiotherapeutic and toxicological localizations of ROS in different topographic-anatomical zones. The paper pays special attention to the singlet oxygen produced by the samples upon microwave treatment, as a physiologically active and highly reactive agent.
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