**2.3 Free radical cause lipid peroxidation**

Lipids are major structural components of the membranes and are highly addictable to oxidation by the presence of reactive double bonds [39]. The malondialdehyde (MDA), product of lipid peroxidation, reacts with low-density lipoproteins and indirectly induced the process of atherosclerosis [40]. The high level of oxidative stress is directly proportional to progression of tumor stages in lungs and pulmonary parenchyma [41]. The lipid peroxides are one of the ROS that enhance the DNA damage through mutations which results in decreased expression of tumor suppressor genes or increased expression of oncogenes [42]. ONOO▬ is the initiator of induction of lipid peroxidation which disrupts the membranes and lipoproteins.

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*Diseases Related to Types of Free Radicals DOI: http://dx.doi.org/10.5772/intechopen.82879*

**3. Neurodegenerative diseases**

**3.2 Free radical cause nitric oxide**

**3.3 Free radical cause lipid peroxidation**

**3.1 Free radical cause peroxynitrites**

These ONOO▬ and MDA collectively act as cytotoxic as well as mutagenic in cancer progression [43]. The formation of oxidative stress due to imbalance of redox system in the cells through increased lipid peroxidation has been associated with human health and diseases, including cancer [44]. The lower levels of cholesterol was detected in cancer cells and suspectible to attack of free radicals enabling the penetration of RONS into the interior of the cell, inducing pro-apoptotic factors [45].

The combined effects of peroxynitrite and sulfur-containing amino acids have been implicated in Parkinson's disease by performing the synergistic toxicity to a neuronal cell line [46]. The protein nitration in the form of nitrotyrosine residues is by the actions of peroxynitrite. Increased concentrations of both protein carbonyls and 3-nitrotyrosine have been reported in various neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) [47]. The decreased activity of antioxidant enzymes with the simultaneous increase in the concentrations of peroxynitrites leads to disturbances of oxidative phosphorylation was observed in the brain mitochondria [48]. The modification of the monomers, destabilize microtubules, and major alterations in neurodegenerative diseases is performed by peroxynitrites [49]. The effects of S-nitrosylation on neuronal excitation are due to stimulation of ionotropic

glutamate receptors and toxic Aβ peptides in Alzheimer's disease [50].

In the lower doses, nitric oxide acts as a neurotransmitter of the neuronal cells, and it exerts antimicrobial activity invading microbes in macrophages [51]. Nitric oxide played an important role in the modulation of CO2-mediated cerebral blood flow [52]. Nitric oxide is a physiological signaling molecule produced from L-arginine by enzyme of nitric oxide synthase (NOS). This enzyme occurs in three forms as neuronal (nNOS), endothelial (eNOS), and inducible nitric oxide synthase (iNOS). It increases the cGMP levels by acting as vasodilator and is involved in the neurotransmission between nervous system cells [53]. The positive association of oxidative stress and neurodegenerative conditions was observed in multiple sclerosis, stroke, and neurodegenerative disorders [54]. The ROS is actively involved in the oxidative damage to amyloid beta peptides, marker in the Alzheimer's disease [55]. The most abundant neurotransmitter in central nervous system is glutamate which acts as the initiator of NO formation, and H2S is highly expressed in brain which is involved in the pathogenesis of various neurological disorders [56].

The brain oxidative damage contributes to AD pathogenesis by the Aβ accumulation and amyloid plaque formation in the Alzheimer's disease of Tg2576 mice [58]. The imbalance of functioning endogenous antioxidant system leads to accumulation of free radicals, which not only induces the process of lipid peroxidation but also plays a central role in neurodegeneration [59]. Lipids are critical for plasticity and function of neuronal development. The abnormalities in lipid metabolism contribute to the pathogenesis of several neurodegenerative disorders like Alzheimer's disease and Parkinson's disease [60]. The relationship between lipid *Antioxidants*

**Figure 4.**

In lung cancer, a high level of NO is linked to chronic stages of cancer cells and protective role in the survival and proliferation of tumor cells by inhibiting apoptosis, increasing cell migration, and invasion [29]. NO and its role in carcinogenesis and tumor progression, as well as dietary chemopreventive agents have NO-modulating properties with safe cytotoxic profile [30]. The nitric oxide synthase 2-mediated production of NO/reactive nitrogen oxide species (RNS) is heavily involved in cancer

Peroxynitrites (ONOO▬) could able to cause DNA strand breaks and oxidize cellular thiol groups in viable rat thymocytes in a dose-dependent fashion [32]. ONOO▬ is actively involved in the disturbances of signaling pathways of epidermal growth factors indirectly induced the process of tumorigenesis [33]. The combined effects of nitric oxide and oxidized LDL forms increase the concentrations of peroxynitrites that leads to glutathionylation of p21 ras proteins which results in aberrant activation of p21 [34]. The S-nitrosylation of PTEN, Bcl2 enhanced DNA mutation, and inhibition of apoptosis results in cell proliferation and cell survival [35]. The peroxynitrite could modify the DNA and increase the DNA adducts which act as antigens is one of the factors for the autoantibody induction in cancer patients [36]. Levels of peroxynitrite and nitrosylhemoglobin can be used as highly informa-

progression and metastasis in different types of tumor (**Figure 4**) [31].

tive markers of disease prognosis and therapeutic approach [37].

Lipids are major structural components of the membranes and are highly addictable to oxidation by the presence of reactive double bonds [39]. The malondialdehyde (MDA), product of lipid peroxidation, reacts with low-density lipoproteins and indirectly induced the process of atherosclerosis [40]. The high level of oxidative stress is directly proportional to progression of tumor stages in lungs and pulmonary parenchyma [41]. The lipid peroxides are one of the ROS that enhance the DNA damage through mutations which results in decreased expression of tumor suppressor genes or increased expression of oncogenes [42]. ONOO▬ is the initiator of induction of lipid peroxidation which disrupts the membranes and lipoproteins.

**2.2 Free radical cause peroxynitrites**

*The role of nitric oxide in various diseases of humans [57].*

**2.3 Free radical cause lipid peroxidation**

**372**

These ONOO▬ and MDA collectively act as cytotoxic as well as mutagenic in cancer progression [43]. The formation of oxidative stress due to imbalance of redox system in the cells through increased lipid peroxidation has been associated with human health and diseases, including cancer [44]. The lower levels of cholesterol was detected in cancer cells and suspectible to attack of free radicals enabling the penetration of RONS into the interior of the cell, inducing pro-apoptotic factors [45].
