Oxidative Stress

Oxidative stress is a general name for the imbalance resulting from the accumulation of free radicals and reactive metabolites that need to be neutralized by antioxidant mechanisms. This imbalance causes damage and disruption to important biomolecules and cells, which have a potential impact on the whole organism (Durackova 2010). There are numerous ailments related to oxidative stress, for example: Alzheimer’s, Parkinson’s, Huntington’s, immune system disorders, amyotrophic lateral sclerosis, diabetes, cancer, cardiovascular disorders, inflammation, chronic kidney disease, acute respiratory distress syndrome, atherosclerosis, neurological disease, obesity, pulmonary fibrosis, and rheumatoid arthritis (Reuter et al. 2010; Pisoschi and Pop 2015; Yan et al. 2020). Moreover, the progressive oxidative damage that is developed by free radicals can expose aging and the development of degenerative diseases. Also, cataracts and atherosclerosis can be exposed due to aging (Percival 1998).

Reactive Oxygen Types

Free radicals are molecular structures. They are molecules that have one or more unpaired electrons in their outermost orbitals and because of this they are unstable and are likely to bond. To the intensive request for consolidating with other radicals or non-radical agents, free oxygen radicals can cause many biological impacts in the body. The formation of exogenous and endogenous free radicals cannot be prevented, but free radicals can be neutralized (Poljsak et al. 2011). Free radicals are constantly produced and being exposed in humans at metabolic processes (cellular respiration) and with the effect of environmental oxidants (drug toxicity, cigarette smoke, ultraviolet radiation, air pollution, intense physical activity, and alcohol) (Sen et al. 2010; Poljsak et al. 2011). Molecular oxygen is the source of ROS and has two unpaired electrons. The oxidation reactions that create ROS occur by enzymes that are known to contain transition metals (such as Fe, Cu). The formation of free radicals is exposed when molecular oxygen gets a single electron transfer. Besides, unpaired electrons containing molecular oxygen play an important role in the formation of ROS (Gutteridge 1994). Hydrogen peroxide (H202), superoxide anion (O2-), single oxygen (1/2 02), and hydroxyl radical (OH). Oxygen molecules such as H202, O2-, 1/2 02, hypochlorous acid (HOC1), and hydroxyl radical (OH) that make up ROS are extremely reactive and have toxic effects on cells. Due to this toxic effect, it also damages the organs (Kohen and Nyska 2002; Pham-Huy et al. 2008; Fransen et al. 2012). In addition, reactive nitrogen types (RNS) and reactive sulfur types (RSS) are free radicals that can also cause damage. Respectively they are derived with the reaction of ROS and nitric oxides, derived with the reaction of ROS and thiols. If these reactive molecules are not neutralized, they can accumulate and cause various complications in the body (Durackova 2010; Corpas and Barroso 2015). On the other hand, free radicals can damage any protein. Therefore, since free radicals damage proteins, they affect the activity of enzymes and the function of the structural protein. In addition, the production of protein hydroperoxides is with the oxidation of proteins. The oxidation of proteins is caused by ROS/RNS that interact with transition metal ions. If proteins are oxidized, they become inactive and are eventually removed. However, these inactive proteins can accumulate in some cases and cause damage due to various diseases as well as aging (Sen and Chakraborty 2011).

Antioxidant Mechanism

We have mentioned that free radicals are continuously produced during normal metabolism in the body and are neutralized by antioxidant defense systems. Antioxidants can remove or delay cell damage by removing free radicals in the cell. The body can produce antioxidants naturally in the body, or they can be obtained from external foods that we eat (Lobo et al. 2010). Antioxidant agents can show their effects against oxidant molecules in four ways; the first of them is the scavenging effect and works by preventing the formation of radicals, they make the formed radicals less harmful. Enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and some metal-binding proteins are examples of antioxidants that have a scavenging effect. The second one is the removal/quenching effects, these effects are formed by compounds that interact with oxidants and inactivate their activities by extinguishing them as a result of transferring hydrogen to them. Examples of these removal/ quenching molecules are vitamins (vitamins A, C, and E), flavonoids, mannitol, anthocyanins, etc. The third effect is the chain-breaking effect, it breaks the reactions that continue as a chain and disable them as a result of binding oxidant molecules to them. Examples of chain-breaking molecules are uric acid, bilirubin, albumin, etc. The fourth effect is the repair effect; it removes the harmful effects of oxidant molecules as a result of repairing the damaged biomolecule. Examples of repairing molecules are DNA repair enzymes, methionine sulfoxide reductase, etc. (Arkan 2011).

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