Group items tagged

The H2O2 produced this way (Reactions 1–3) seems to be key to ascorbate's antitumor effect because H2O2 causes cancer cells to undergo apoptosis, pyknosis, and necrosis

In contrast, normal cells are considerably less vulnerable to H2O2

The reason for the increased sensitivity of tumor cells to H2O2 is not clear but may be due to lower antioxidant defenses

In fact, a lower capacity to destroy H2O2—e.g., by catalase, peroxiredoxins, and GSH peroxidases—may cause tumor cells to grow and proliferate more rapidly than normal cells in response to low concentrations of H2O2

These observations, combined with the inhibitory effect on xenograft growth, provide the proof of concept that millimolar concentrations of extracellular ascorbate, achievable by i.p. injection or i.v. infusion in experimental animals and humans, respectively, exert pro-oxidant, antitumor effects in vivo.

They also show that the concentration of the ascorbyl radical correlates with the concentration of H2O2 in interstitial fluid, whereas no H2O2 can be detected in blood or plasma

The hydroperoxyl radical () plays an important role in the chemistry of lipid peroxidation

The is a much stronger oxidant than superoxide anion-radical

Lipid peroxidation can be described generally as a process under which oxidants such as free radicals or nonradical species attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs) that involve hydrogen abstraction from a carbon, with oxygen insertion resulting in lipid peroxyl radicals and hydroperoxides as described previously

under medium or high lipid peroxidation rates (toxic conditions) the extent of oxidative damage overwhelms repair capacity, and the cells induce apoptosis or necrosis programmed cell death

The overall process of lipid peroxidation consists of three steps: initiation, propagation, and termination

Once lipid peroxidation is initiated, a propagation of chain reactions will take place until termination products are produced.

The main primary products of lipid peroxidation are lipid hydroperoxides (LOOH)

Among the many different aldehydes which can be formed as secondary products during lipid peroxidation, malondialdehyde (MDA), propanal, hexanal, and 4-hydroxynonenal (4-HNE) have been extensively studied

MDA has been widely used for many years as a convenient biomarker for lipid peroxidation of omega-3 and omega-6 fatty acids because of its facile reaction with thiobarbituric acid (TBA)

MDA is one of the most popular and reliable markers that determine oxidative stress in clinical situations [53], and due to MDA’s high reactivity and toxicity underlying the fact that this molecule is very relevant to biomedical research community

4-HNE is considered as “second toxic messengers of free radicals,” and also as “one of the most physiologically active lipid peroxides,” “one of major generators of oxidative stress,” “a chemotactic aldehydic end-product of lipid peroxidation,” and a “major lipid peroxidation product”

MDA is an end-product generated by decomposition of arachidonic acid and larger PUFAs

Identifying in vivo MDA production and its role in biology is important as indicated by the extensive literature on the compound (over 15 800 articles in the PubMed database using the keyword “malondialdehyde lipid peroxidation” in December 2013)

MDA reactivity is pH-dependent

When pH decreases MDA exists as beta-hydroxyacrolein and its reactivity increases

MAA adducts are shown to be highly immunogenic [177–181]. MDA adducts are biologically important because they can participate in secondary deleterious reactions (e.g., crosslinking) by promoting intramolecular or intermolecular protein/DNA crosslinking that may induce profound alteration in the biochemical properties of biomolecules and accumulate during aging and in chronic diseases

MDA is an important contributor to DNA damage and mutation

This MDA-induced DNA alteration may contribute significantly to cancer and other genetic diseases.

Dietary intake of certain antioxidants such as vitamins was associated with reduced levels of markers of DNA oxidation (M1dG and 8-oxodG) measured in peripheral white blood cells of healthy subjects, which could contribute to the protective role of vitamins on cancer risk

4-HNE is an extraordinarily reactive compound