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Among the more susceptible targets are polyunsaturated fatty acids. Abstraction of a hydrogen atom initiates the process of lipid peroxidation Figure 2.

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Numerous products are formed, presenting special analytical problems. The choice is between simple, nonspecific assays for classes of lipid peroxidation products e. A sensitive and specific colorimetric assay based on measurement of malondialdehyde and 4-hydroxyalkenals is a good compromise. Proteins are modified in structure and function by radical reactions. Metal-catalyzed protein oxidation results in addition of carbonyl groups or cross-linking or fragmentation of proteins.

Lipid peroxidation aldehydes can react with sulfhydryl cysteine or basic amino acids histidine, lysine. Similarly, modification of individual nucleotide bases, single-strand breaks and cross-linking are the typical effects of reactive oxygen species on nucleic acids.

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Mammalian cells possess elaborate defense mechanisms to detoxify metabolize radicals Figure 3. Redox-active metals, such as iron, bind to storage and transport proteins e. All Rights Reserved.

Free Radicals: From Health to Disease

Skip to main content. Figure 1. What is a Free Radical?

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A free radical is an atom or group of atoms that has an unpaired electron and is therefore unstable and highly reactive. When the outermost shell is full, the atom is stable and tends not to engage in chemical reactions. When, however, the outermost shell is not full, the atom is unstable. It will try and stabilize itself by either gaining or losing an electron to either fill or empty its outermost shell.

Or it will share its electrons by bonding with another atom that is also looking to complete its outer shell. It is not uncommon for an atom to complete its outer shell by sharing an electron with another atom and forming a bond. Free radicals form when one of these weak bonds between electrons is broken and an uneven number of electrons remain.

This means the electron is unpaired, making it chemically reactive. For example they serve in immune defense because leucocytes and macrophages utilize their bactericidal effects: they produce free radicals and thus destroy bacteria and other foreign substances.

Free Radical | Definition of Free Radical by Merriam-Webster

Immune-relevant cells also use the reactive potential of ROS as a cellular defense mechanism against entering pathogens to kill bacteria, viruses and degenerated cells. Radicals also fulfill important physiological functions such as regulating the vascular tone and those cell functions controlled by oxygen concentration. They also influence signal transmission mechanisms and trigger oxidative stress responses as well as apoptosis The capacity of cellular defense mechanisms is limited. Oxidative stress can therefore lead to malfunction and even to cell death.

Oxidative stress is the result of an imbalance between the intracellular production of free radicals and the cellular defense mechanisms.

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The balance between oxidants and antioxidants can be disrupted by an increase in free radicals or a reduction of anti-oxidative substances. Oxidative stress can trigger a number of potentially damaging biochemical reactions 9. Studies show that the production of radicals is directly involved in the oxidative destruction of macromolecules such as lipids, proteins and nucleic acids. Under certain conditions, phagosomes vesicles in which bacteria, for example, are taken up 10 of macrophages can degenerate and release their contents into other cell compartments, damaging DNA through oxidative reactions.

Chronic infections can therefore trigger chronic inflammatory reactions by promoting permanent phagocytic activity of macrophages. Moreover, free radicals play a role in many degenerative diseases and cell aging processes 3. Free radicals and their derivates, along with reactive non-radicals that can be attributed to radicals, are always present in living systems in relatively low and balanced amounts.

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The concentration of free radicals depends on their production and their clearance. Clearance is controlled by various enzymes and non-enzymatic antioxidants for example vitamins E, A, C and glutathione. Cells are in a stable state when the rate of ROS production and the anti-oxidation capacity are in balance.

This is referred to as a balanced redox capacity. This balance can be disrupted either by increased ROS production or by the reduced capacity of the antioxidants. As free radicals can donate an electron to a suitable receptor reduction reaction or can bond their unpaired electron with a suitable donor oxidation reaction , free radicals play an important role in maintaining the redox balance in cells.

Depending on the duration and strength of the imbalance which can be temporally limited , the redox regulation of the cell fulfills a compensatory function. This physiological mechanism is termed redox homeostasis.


When, however, a constant production of free radicals is triggered, for example by oxidative stress, then the redox homeostasis becomes unbalanced because the cellular mechanisms are no longer capable of establishing the normal levels. This can persistently change signal transmission, but also lead to changes on gene and protein levels of the cells and thus promote so-called oxidative conditions or processes. This includes virtually all complex molecules that can gain a single electron DNA, proteins, lipids and carbohydrates and thus be damaged by highly reactive radicals.

When ROS is consistently elevated over a longer time period chronic conditions free radicals can cause damage and lead to pathological conditions. Various in vitro and in vivo studies show that free radical formation can be triggered by nanoparticles fullerenes, carbon nanotubes, quantum dots, emission particles 12, Nanoparticles can be taken up actively phagocytosis by certain cells macrophages and initiate ROS formation 14, Passive cellular uptake of particles has also been documented.

#11 - Cellular mechanisms of cell injury - Free radical damage, Reactive oxygen species, glutathione

The decisive question, however, is whether more ROS is formed per cell when more particles are taken up. It is unclear whether they can produce elevated ROS levels in this configuration. ROS can also develop directly on the surface of the particles, although this depends on particle structure metallic particles, for example, function as catalysts.