Review article
The role of antioxidants in the chemistry of oxidative stress: A review

https://doi.org/10.1016/j.ejmech.2015.04.040Get rights and content

Highlights

  • Oxidative stress initiates structure and function alterations of key biomolecules.

  • The oxidant/antioxidant unbalance activates factors responsible for cell injury.

  • Reactive oxygenated/nitrogenated species become the source of disease occurrence.

  • General and specific antioxidant mechanisms prevent the oxidative damage.

  • Prooxidative effects may occur in some cases, like in the presence of transition metal ions.

Abstract

This Review Article is focused on the action of the reactive oxygenated species in inducing oxidative injury of the lipid membrane components, as well as on the ability of antioxidants (of different structures and sources, and following different mechanisms of action) in fighting against oxidative stress.

Oxidative stress is defined as an excessive production of reactive oxygenated species that cannot be counteracted by the action of antioxidants, but also as a perturbation of cell redox balance. Reactive oxygenated/nitrogenated species are represented by superoxide anion radical, hydroxyl, alkoxyl and lipid peroxyl radicals, nitric oxide and peroxynitrite.

Oxidative stress determines structure modifications and function modulation in nucleic acids, lipids and proteins. Oxidative degradation of lipids yields malondialdehyde and 4-hydroxynonenal, but also isoprostanes, from unsaturated fatty acids. Protein damage may occur with thiol oxidation, carbonylation, side-chain oxidation, fragmentation, unfolding and misfolding, resulting activity loss. 8-hydroxydeoxyguanosine is an index of DNA damage.

The involvement of the reactive oxygenated/nitrogenated species in disease occurrence is described. The unbalance between the oxidant species and the antioxidant defense system may trigger specific factors responsible for oxidative damage in the cell: over-expression of oncogene genes, generation of mutagen compounds, promotion of atherogenic activity, senile plaque occurrence or inflammation. This leads to cancer, neurodegeneration, cardiovascular diseases, diabetes, kidney diseases.

The concept of antioxidant is defined, along with a discussion of the existent classification criteria: enzymatic and non-enzymatic, preventative or repair-systems, endogenous and exogenous, primary and secondary, hydrosoluble and liposoluble, natural or synthetic. Primary antioxidants are mainly chain breakers, able to scavenge radical species by hydrogen donation. Secondary antioxidants are singlet oxygen quenchers, peroxide decomposers, metal chelators, oxidative enzyme inhibitors or UV radiation absorbers.

The specific mechanism of action of the most important representatives of each antioxidant class (endogenous and exogenous) in preventing or inhibiting particular factors leading to oxidative injury in the cell, is then reviewed. Mutual influences, including synergistic effects are presented and discussed. Prooxidative influences likely to occur, as for instance in the presence of transition metal ions, are also reminded.

Section snippets

The concept of oxidative stress

Oxidative stress was defined as the lack of balance between the occurrence of reactive oxygen/nitrogen species (ROS/RNS) and the organism's capacity to counteract their action by the antioxidative protection systems [1].

Oxidative stress emerges from an enhanced ROS/RNS generation or from a decay of the antioxidant protective ability, being characterized by the reduced capacity of endogenous systems to fight against the oxidative attack directed towards target biomolecules. Its severeness is

Definitions and classifications – discussion of the criteria up to now

The concept of biological antioxidant refers to any compound that, when present at a lower concentration compared to that of an oxidizable substrate, is able to either delay or prevent the oxidation of the substrate [19], [67]. Antioxidant functions imply lowering oxidative stress, DNA mutations, malignant transformations, as well as other parameters of cell damage. Epidemiological studies proved antioxidants' ability to contain the effects of reactive oxygen species activity, and diminish the

Critical view on the oxidant-antioxidant balance

While redox biology implies a slight increment of the reactive oxygenated species level, meant to activate signaling pathways, oxidative stress involves elevated ROS amounts, resulting in the impairment of nucleic acids, protein or lipids [286]. Although it has been confirmed that fruits and vegetables represent secure sources of antioxidant vitamin amounts lowering oxidative stress, it has been reported that high antioxidant supplementation can prove unsafe [287]. The results of randomized

Conclusions

Oxidative stress results from an excessive reactive oxygen species generation, and consists in an imbalance of oxidative to reducing species, being also better defined as a perturbation of redox signalling. The action of reactive oxygenated/nitrogenated species (superoxide anion radical, hydroxyl, alkoxyl, lipid peroxyl radicals, nitric oxide and peroxynitrite) results in alterations and function modulations of key biomolecules.

The marker of DNA damage is represented by 8-hydroxydeoxyguanosine.

Conflicts of interest

There are no conflicts of interest involved, and no fundings supporting this paper.

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