What is the relationship between free radicals and the inflammation process during Chronic diseases?

OxInflammation process is a complex and systemic event that occurs after cellular and tissue injury. The knowledge about both processes is that they coexist, but already known that possibly the inflammatory response is responsible for the generation of a pro-oxidative environment due to the production of Free radicals and Reactive Oxygen species (ROS), especially in chronic diseases. In normal tissue occurs the activation of efficient machinery able to control the oxidative stress, however, in chronic diseases occur a failure to maintain the physiological redox steady-state and the perturbation of this physiological adaptive dynamic equilibrium, induced by a persistent challenge or inappropriate feedback response, leads to the inflammatory state.  Therefore, Free radicals and ROS are involved in benefit (redox signaling) and harm (biological damage) and there is a limit extremely delicate, and easily influential between the benefits and damage. During the inflammation process, this limit is quickly overlapping, since oxidants molecules can originate from the activity of lipoxygenases, cyclooxygenases, xanthine oxidase, phagocytic, and non-phagocytic nicotinamide adenine dinucleotide phosphate oxidases (NOXs) and also from Fenton/Haber—Weiss reactions catalyzed by transition metals and easily overlapping the limit between benefit and harm. In this sense, exogenous stressors (pollution, smoking, fat diet, etc.) or endogen factors (diseases and inflammation itself) are potentially able to disrupt this finely tuned homeostasis, inducing the formation of oxidants promoting a lot of inflammatory diseases. On the other hand, ROS can activate transcription factors involved in the inflammatory process such as NF-kB, AP-1, and HIF-1a. In addition, Free radicals and ROS can act as second messengers and promote the activation of the MAPK cascade, responsible for cell migration, cell proliferation, and neoangiogenesis. Therefore, is important to create an interdisciplinary platform involving morphological, physiological, biochemical, molecular, and pathological issues to discuss the identification and relevance, and especially therapeutic potential of new compounds, involving Free Radicals generation and Inflammation process in chronic diseases.

Biochemistry Biomarkers Carcinogenesis Cell biology Ecotoxicology
Rômulo Novaes
Chronic inflammatory processes are caused by persistent stimuli that maintain the constant activation of cellular and humoral inflammatory mechanisms. In these prolonged processes, inflammatory mediators activate cell signaling pathways linked to the biosynthesis of radical and non-radical reactive species, which cannot be completely neutralized, causing continuous oxidative stress. Oxidative stress promotes molecular damage to biomolecules in cells and extracellular matrix, especially in lipids, proteins and DNA. When oxidized, these molecules act as pro-inflammatory signalers, feeding back tissue inflammation that cannot resolve. Thus, anti-oxidant products can attenuate oxidative stress, decreasing the activation of the immune response so that the chronic inflammatory process can be resolved from the action of regulatory cells and molecules, such as TCD4+ lymphocytes and IL-1O.
mkgoodness (Khatami, Mahin)
Persistent chronic inflammation was suggested as a common denominator in the genesis of nearly all age-associated health conditions or site-specific cancer.  We defined acute inflammation as a highly regulated defense mechanism of immune system, possessing two well-balanced and biologically opposing arms termed apoptosis (‘Yin’) and wound healing (‘Yang’) processes. Chronic inflammation (oxidative stress, sub clinical) is loss of balance between ‘Yin’ and ‘Yang’ that induce expression, co-expression or ‘mismatched’ pro-inflammatory (apoptotic) and anti-inflammatory (wound healing) mediators in the microenvironment of tissues (‘immune meltdown’). Unresolved inflammation could initiate genesis of many age-associated chronic illnesses such as autoimmune and neurodegenerative diseases or tumors/cancers. Interrelated co-morbidity risk factors that participate in biological shifts of growth-arresting (‘tumoricidal’) or growth-promoting (‘tumorigenic’) properties of immune cells (innate and adaptive) and also alter non-immune systems (vasculature, hormonal, neuronal, metabolic, genomic) activities lead to genesis of chronic inflammatory diseases and cancer.  Cumulative exposures to low level carcinogens and environmental hazards or high energy electronic devices (EMF; 5G) or pathogen-specific vaccines are triggers (antigen-mitochondrial overload) or “seeds of immune destruction” that create mini electrical shocks (molecular sinks holes) in highly synchronized and regulated immune network and retard time-energy-dependent biorhythms in organs resulting in causes, exacerbations or consequences of mild, moderate or severe immune disorders. 
Aline Leão
One of the natural results of metabolism is the formation of free radicals in the mitochondria. However, in some circumstances, such as in cases of inflammation, the production of reactive oxygen species can exceed antioxidant products, causing an imbalance known as "oxidative stress". This process is harmful to cells and promotes increased inflammation, so that one process aggravates the other in a cycle.
Free radicals are naturally produced by the body and participate in many processes in our body, but under certain conditions they can cause high production of reactive oxygen species, exceeding our body's natural ability to deal with them, which can result in oxidative stress. High concentrations of reactive oxygen species are involved in the activation of the NF-κB pathway with the maintenance of the inflammatory process, and can lead to damage to macromolecules. This activated pathway allows the transcription of inflammatory genes, which with their excess, leads to a cascade of damage to cells. Thus, they are intertwined with the chronic disease process and its causes, as well as being directly related to the aging process. They are the target of numerous researches and advances in the medical and pharmaceutical area, with the objective of controlling the activation and/or deactivation of the pathways influenced by them and the understanding of certain diseases.
Fernanda Lopes
Oxidative stress and inflammation are coexisting and interrelated ROS events, regulating each other in vicious feedback. In parallel and antagonistically, oxidative stress is activated with the presence of inflammation, and the balance between ROS production and antioxidant defenses is important for the resolution of inflammatory diseases, as well as efficient tissue repair initiating chemical signaling cascades and activation of survival pathways, such as NFkB, IKβ, IP3 and IFN-γ. During the injury, there is a reduction in oxygen and ATP and an increase in ROS produced by the cell during the respiratory burst, amplified in the inflammatory process, causing more oxidative stress. Oxidative stress then, resulting from the imbalance between oxidants and antioxidants, leads to disruption of redox signaling causing molecular damage and the body's inability to neutralize and protect against this damage. Thus, low levels of ROS activate signaling pathways as part of the inflammatory response facilitating the elimination of toxins and pathogens, in addition to triggering the expression of antioxidant genes, but when produced for prolonged periods, they can promote oxidative stress and chronic diseases related to inflammation. The path to successful targeting of inflammation and oxidative stress combines with a common effort in the pursuit of tissue repair. Thus, inflammation and oxidative stress are positive and necessary roles in the biological healing response.
The production of free radicals by the body occurs through normal physiology and is a result of metabolism, with the mitochondria playing a leading role in the generation of these radicals endogenously, and may also originate from the cytoplasm and cell membranes. However, an imbalance between the production of free radicals and antioxidant agents characterizes oxidative stress, which is also associated with chronic diseases due to the destruction of molecules, since the cell membrane is one of the sites most affected by free radicals as a result of peroxidation. of lipids that refers to the oxidative destruction of structures that contain polyunsaturated fatty acids, and that lead to changes in these structures as well as in the permeability of membranes. As a result of these processes, there is impairment in the selectivity of ion exchange and release of substance from organelles such as hydrolytic enzymes from lysosomes, resulting in the emergence of cytotoxic products culminating in cell death.

André de Souza
The excess of free radicals present in chronic inflammation, mainly due to the release of digestive enzymes present in phagolyosomes, is harmful to tissue due to time and low levels of antioxidant agents. Associated with this, some inactively secreted extracellular matrix metalloproteases (ECM) are activated by abundant free radicals in an area of inflammation, increasing the degradation of ECM proteins, further impairing tissue repair. In addition to chronic inflammation, other stimuli can cause damage by releasing free radicals: (a) chemical substances produce free radicals when they are metabolized in cells; (b) ionizing radiations generate them by the ionization of water; (c) cigarette smoke and some oxidized foods contain them.
Mariáurea Sarandy
The formation of free radicals that occurs in the respiratory chain under normal conditions, are inactivated in loco and do not leave the mitochondria. However, in chronic inflammation, characterized by the persistence of the inflammatory agent and by containing areas of inflammatory activity, with cellular exudate predominantly of mononuclear cells (macrophages and lymphocytes), can release oxidase enzymes that were activated during the process of antigen internalization, converting molecular oxygen into superoxide anion, hydrogen peroxide and free radicals. Transcription factors (eg, NFkB and AP-1), which activate the transcription of genes encoding antioxidant molecules and chaperones, have their expression potentiated by free radicals when present in small amounts (low redox state), however, with the persistent stimulus of chronic inflammation, it causes these free radicals released culminates in the increase of tissue damage and its evolution to necrosis is inevitable if no therapeutic intervention occurs.
Leonardo Silveira
Inflammation is a pathophysiological process that occurs as the body's response to the invasion of infectious agents or physical injury, and free radicals play an important role in infectious and inflammatory processes. 
Free radicals are produced naturally or by some biological dysfunction and can be harmful to the body. Its excess has harmful effects, inducing events such as peroxidation of membrane lipids and aggression to tissue and membrane proteins, enzymes, carbohydrates and DNA, thus being linked to various health problems and inducing the emergence of various diseases.Thus, oxidative stress is a state of vulnerability of the defense system in which there is an excessive production of reactive oxygen species that exceeds the body's antioxidant defense capacity, being, therefore, subject to infectious and degenerative diseases.Therefore, there is a need for the body to have antioxidants to fight these radicals, as antioxidant compounds can reduce oxidative stress, minimizing the incidence of diseases. 

Silvânia Pelinsari
Excessive generation of free radicals promotes an imbalance between oxidant and antioxidant products within cells, promoting the process of oxidative stress . Excess ROS can oxidize biomolecules including RNA/DNA, lipids or proteins, or they can structurally modify proteins and genes to trigger signaling cascades that can lead to the initiation of the inflammatory response. Inflammatory stimuli can trigger the activation of intracellular signaling pathways involved in the expression of inflammatory mediators causing the release of microbial products and cytokines, including interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor, showing that there is a relationship between inflammation and oxidative stress. So there is a vicious cycle created by oxidative stress and inflammation that participate in numerous diseases. Oxidative stress can elevate the expression of pro-inflammatory genes via signaling pathways such as NFkB, while infiltrating inflammatory cells and cytokines such as IL-6 produce more oxidative stress.

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