**Abstract**

Quantification of reactive oxygen species, is perplexing either *in vivo* or *in vitro* due to their short half-lives. Consequently, to define the magnitude of oxidative stress, the more stable oxidation products can be measured in biological samples. The oxidative stress leads to the lipid peroxidation that involves the initiation, termination and propagation of lipid radicals, wherein, the process involves the oxygen uptake, rearrangement of the double bonds in unsaturated lipids, that leads to polyunsaturated fatty acid deterioration. Subsequently, the toxic signaling end products are considered as biomarkers of free radicals that act both as signaling molecules and as cytotoxic products cause covalent alteration of lipid peroxidation products. The use of validated signaling mechanism (s) of Lipid peroxidation and products derived thereof exhibits its use clinical practice and basic clinical research as well as in clinical practice has become common place, and their presence as endpoints in clinical trials is now broadly accepted. This knowledge can be used to diagnose disease earlier, or to prevent it before it starts. The signaling markers can be used to excel the effectiveness of the prevailing medicines and to improve the new medicines.

**Keywords:** lipid peroxidation, isoprostanes, malondialdehyde, Alzheimer's disease, oxidative stress

#### **1. Introduction**

Lipids are of two types: Polar and Non-polar. The polar lipids (Triglycerides), store in various cells but especially in adipose (fat) tissue, are usually the main source of energy for mammals. Polar lipids are underlying segments of cell layers, where in it contributesfor thedevelopment of permeability barrier of cells and subcellular organelles in the form of a lipid bilayer [1]. The glycerol-based phospholipid is the significant type of membranous lipid bilayer and it is evidenced by the element that membrane lipids may regulates the biologicalfunctions of a membrane organelle by amending its biophysical characteristics, such as the divergence and absorptivity [2]. Lipids and its metabolite productsfacilitates a key ingredient in understanding the biology and serve as a signaling biomolecules in the diagnosis of diseases [3]. However, theleading enzymes that generate as lipid-signaling biomarkers are lipoxygenase, that intervene hydroperoxyeicosatetraenoic acids (HPETEs), lipoxins, leukotrienes, or hepoxilins biosynthesis after oxidation of fatty acids/arachidonic

acid (AA), cyclooxygenase that yields prostaglandins, and cytochrome P-450 (CYP) that produces epoxyeicosatrienoic acids, leukotoxins, thromboxane, or prostacyclin respectively [4, 5]. The signaling lipid biomarkers recruitsvia stimulation of a variety of receptors, including nuclear and G protein-coupled receptors. Moreover, several othertypes of lipidmetabolites have been recognized as potent intracellular signal transduction molecules viz; i) diacylglycerol (DAG) and inositol phosphates (IPs) were derived from the phosphatidylinositol phosphates. DAG is a transcription nuclear factor-kB (NF-kB) which promotes cell survival and proliferation and also a physiological activator of protein kinase C [6, 7] and a small G protein [8]. On the other hand, IPs (lipid derived metabolites) are anextremelystimulatingthat intricate in signal transduction, results in activation of mTORand Akt [9], and calcium homeostasis [10, 11]; ii) Sphingolipid derived from ceramide (sphingosine-1-phosphate), is aeffective messenger molecule engaged in proliferation, adhesion, migration and alsoregulates calcium mobilization at molecular and cellular level of the organism [12–14]; iii) oxidative stress induced fatty acid derived eicosanoid and prostaglandins involved in inflammation [15, 16] and immunity [17]; iv) phosphotidylserine, (a phospholipid) that plays crucial role in a number of signaling pathways, includes fusogenic proteins, kinases and small GTPases [18]; v) the sex and growth hormones such as testosterone, progesterone, estrogen and cortisol that monitored a host body activities such as reproduction, blood pressure metabolism, inflammation, oxidative stress response etc. [19].

Molecular mechanism of lipid damage: The process of lipid peroxidation (LPO), is the resultant of oxidative stress and free radical production. Specifically, reactive oxygen species (ROS) attack polyunsaturated fatty acids (PUFAs) of cellular membranes and leads tothe insult of functional and/or structural integrity of cell membranes, subsequentlyproducing4-hydroxy-2-noneal (HNE), malondialdehyde (MDA) and acrolein (a group of α, β-unsaturated highly reactive aldehyde) [20, 21]. Therefore, these strong reactive aldehydes are significantlydiffusive, able to attack and form covalent linkages with auxiliary cellular constituents. Moreover, the lipid peroxidation process continues asself-propagation followed by initiation of chain reactions and termination either with complete substrate utilization or through interaction with antioxidants such as tocopherol (Vitamin E). Neuroprostanes (neuroPs), isoprostanes (IsoPs) are the additional LPO products of arachidonic acid and docosahexaenoic acid (DHA), that are quantified in the biological fluids to diagnose the severity of the disease. Furthermore, the cyclized fatty acids proliferate further and metabolize the cellular membrane components, mainly lipids and proteins, and propagates the other LPO products in the body fluids [22].

Quantification of reactive oxygen species, is perplexing either *in vivo* or *in vitro* due to their short half-lives. Consequently, to define the magnitude of oxidative stress, the more stable oxidation products can be measured in biological samples. The oxidative stress leads to the lipid peroxidation that involves the initiation, termination and propagation of lipid radicals, wherein, the process involves the oxygen uptake, rearrangement of the double bonds in unsaturated lipids, that leads to polyunsaturated fatty acid deterioration. Subsequently, the toxic signaling end products are considered as biomarkers of free radicals that act both as signaling molecules and as cytotoxic products cause covalent alteration of lipid peroxidation products [23]. In respect of their oxidative-induced damage properties, these compounds are considered as disease mediators in the pathophysiology of many neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), Diabetes, Atherosclerosis, Chronic inflammation, Asthma and liver injury that serve as potential biomarkers in the signaling mechanism in diagnosis of diseases [24]. Thus, it is necessary to understand the oxidative deterioration of lipids in a sequential five-step procedure

*Lipid Peroxidation: A Signaling Mechanism in Diagnosis of Diseases DOI: http://dx.doi.org/10.5772/intechopen.99706*

**Figure 1.** *Oxidative deterioration of lipids.*

in which oxidants, either radical or non-radical species, attack lipids containing C-C double bonds [25, 26]. On the contrary of enzyme-based lipid metabolism, lipid peroxidation does follow a non-enzymatic process that continues in ahystericalmode: Initiation, propagation and termination (**Figure 1**) [27].
