The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state

Abstract

Remarkable interest has risen in the idea that oxidative/nitrosative stress is mediated in the etiology of numerous human diseases. Oxidative/Nitrosative stress is the result of an disequilibrium in oxidant/antioxidant which reveals from continuous increase of Reactive Oxygen and Reactive Nitrogen Species production. The aim of this review is to emphasize with current information the importance of antioxidants which play the role in cellular responce against oxidative/nitrosative stress, which would be helpful in enhancing the knowledge of any biochemist, pathophysiologist, or medical personnel regarding this important issue. Products of lipid peroxidation have commonly been used as biomarkers of oxidative/nitrosative stress damage. Lipid peroxidation generates a variety of relatively stable decomposition end products, mainly α, β-unsaturated reactive aldehydes, such as malondialdehyde, 4-hydroxy-2-nonenal, 2-propenal (acrolein) and isoprostanes, which can be measured in plasma and urine as an indirect index of oxidative/nitrosative stress. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative/nitrosative stress or its consequences. They may act from directly scavenging free radicals to increasing antioxidative defences. Antioxidant deficiencies can develop as a result of decreased antioxidant intake, synthesis of endogenous enzymes or increased antioxidant utilization. Antioxidant supplementation has become an increasingly popular practice to maintain optimal body function. However, antoxidants exhibit pro-oxidant activity depending on the specific set of conditions. Of particular importance are their dosage and redox conditions in the cell.

Keywords: Antioxidants; Oxidative/Nitrosative stress; Reactive oxygen and reactive nitrogen species.

Fig. 1

Endogenous sources of reactive oxygen and reactive nitrogen species (ROS/RNS)

Fig. 2

Some cellular signaling pathways in mammals. Under normal conditions (elevated intracellular reduced potential), nuclear factor erythroid 2-related factor 2 (Nrf2) is stabilized through binding to Keap-1 in the cytoplasm. Under oxidative/nitrosative stress, thiol groups in Keap-1 are oxidized (e.g., S-S cross-links) causing the dissociation of Nrf2, translocation to the nucleus, and binding to the antioxidant-responsive elements (ARE). Depending upon the binding site present in the promoter region, different antioxidant genes are induced

Fig. 3

Antioxidant defenses in the organism

Fig. 4

Chemical structure of the tocopherols

Fig. 5

The oxidation-reduction (redox) reaction of vitamin C, molecular forms in equilibrium. L-dehydroascorbic acid also possesses biological activity, due to that in the body it is reduced to form ascorbic acid

Fig. 6

Oxidized and reduced forms of lipoic acid

Fig. 7

Structure of N-acetyl cysteine (NAC) depicting (1) two chelating sites (thiol and hydroxyl) and (2) deacetylation responsible for its antioxidant potential due to the generation of glutathione

Fig. 8

Chemical structure of melatonin

Fig. 9

Chemical structure of selected carotenoids

Fig. 10

Chemical structure of some flavonoids