Role of free radicals in cancer pdf

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Model of the antioxidant metabolite glutathione. The yellow sphere is the redox-active sulfur atom that provides antioxidant activity, while the red, blue, white, and dark grey spheres represent oxygen, nitrogen, hydrogen, and carbon atoms, respectively. An antioxidant is a molecule that inhibits the oxidation of other molecules. Antioxidant dietary supplements do not improve health nor are they effective in preventing diseases. Industrial antioxidants have diverse uses, including preservatives in food and cosmetics, and oxidation inhibitors in fuels. Although certain levels of antioxidant vitamins in the diet are required for good health, there is considerable debate on whether antioxidant-rich foods or supplements have anti-disease activity. Polyphenols, which often have antioxidant properties in vitro, are not necessarily antioxidants in vivo due to extensive metabolism.

Tirilazad is an antioxidant steroid derivative that inhibits the lipid peroxidation that is believed to play a key role in neuronal death in stroke and head injury. Similarly, the designed antioxidant NXY-059 exhibited efficacy in animal models, but failed to improve stroke outcomes in a clinical trial. As of November 2014, other antioxidants are being studied as potential neuroprotectants. A 2016 systematic review examined antioxidant medications, such as allopurinol and acetylcysteine, as add on treatment for schizophrenia. A 2000 review reported that vitamin E supplementation provided no benefits to physical performance among athletes.

Antioxidant supplementation may reduce the cardiovascular benefits of exercise. Structure of the metal chelator phytic acid. Nonpolar antioxidants such as eugenol—a major component of oil of cloves—have toxicity limits that can be exceeded with the misuse of undiluted essential oils. These harmful effects may also be seen in non-smokers, as a recent meta-analysis including data from approximately 230,000 patients showed that β-carotene, vitamin A or vitamin E supplementation is associated with increased mortality but saw no significant effect from vitamin C. While antioxidant supplementation is widely used in attempts to prevent the development of cancer, antioxidants may interfere with cancer treatments, since the environment of cancer cells causes high levels of oxidative stress, making these cells more susceptible to the further oxidative stress induced by treatments.

A paradox in metabolism is that, while the vast majority of complex life on Earth requires oxygen for its existence, oxygen is a highly reactive molecule that damages living organisms by producing reactive oxygen species. The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species. In this process, the superoxide anion is produced as a by-product of several steps in the electron transport chain. The relative importance and interactions between these different antioxidants is a very complex question, with the various metabolites and enzyme systems having synergistic and interdependent effects on one another. Some compounds contribute to antioxidant defense by chelating transition metals and preventing them from catalyzing the production of free radicals in the cell. Uric acid is by far the highest concentration antioxidant in human blood. Uric acid has the highest concentration of any blood antioxidant and provides over half of the total antioxidant capacity of human serum.

The free radical mechanism of lipid peroxidation. Glutathione is a cysteine-containing peptide found in most forms of aerobic life. It is not required in the diet and is instead synthesized in cells from its constituent amino acids. Vitamin E is the collective name for a set of eight related tocopherols and tocotrienols, which are fat-soluble vitamins with antioxidant properties. It has been claimed that the α-tocopherol form is the most important lipid-soluble antioxidant, and that it protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction. This removes the free radical intermediates and prevents the propagation reaction from continuing.

However, the roles and importance of the various forms of vitamin E are presently unclear, and it has even been suggested that the most important function of α-tocopherol is as a signaling molecule, with this molecule having no significant role in antioxidant metabolism. Antioxidants that are reducing agents can also act as pro-oxidants. For example, vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide, however, it will also reduce metal ions that generate free radicals through the Fenton reaction. The relative importance of the antioxidant and pro-oxidant activities of antioxidants is an area of current research, but vitamin C, which exerts its effects as a vitamin by oxidizing polypeptides, appears to have a mostly antioxidant action in the human body.

That is, paradoxically, agents which are normally considered antioxidants can act as conditional pro-oxidants and actually increase oxidative stress. Besides ascorbate, medically important conditional pro-oxidants include uric acid and sulfhydryl amino acids such as homocysteine. Typically, this involves some transition-series metal such as copper or iron as catalyst. Some antioxidant supplements may promote disease and increase mortality in humans under certain conditions. Enzymatic pathway for detoxification of reactive oxygen species. As with the chemical antioxidants, cells are protected against oxidative stress by an interacting network of antioxidant enzymes. SOD enzymes are present in almost all aerobic cells and in extracellular fluids.

Catalases are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor. Decameric structure of AhpC, a bacterial 2-cysteine peroxiredoxin from Salmonella typhimurium. Peroxiredoxins are peroxidases that catalyze the reduction of hydrogen peroxide, organic hydroperoxides, as well as peroxynitrite. Proteins related to thioredoxin are present in all sequenced organisms.