**4. Lipid peroxidation metabolites as influential signaling biomarkers in asthma and airway inflammation**

Oxidative stress at molecular and cellular level can have many detrimental effects on airway function, including airway smooth muscle contraction, induction of airway hyper responsiveness, mucus hypersecretion, vascular exudation and shedding of epithelial cells. Furthermore, ROS can induce cytokine and chemokine production through induction of the oxidative stress-sensitive transcription of nuclear factor–kB in bronchial epithelial cells [53]. Recently discovered series of bioactive prostaglandin (PF)F2-like compoundswere produced independently of the cyclooxygenase enzymes via the peroxidation of arachidonic acid, catalyzed by free radicals. The pathway leads to formation of 64 isomeric structures, of which 8-iso-PGF2α is most well characterized. Evidence suggests that 8-iso-PGF 2α may act in part through the vascular thromboxane A2/PGH2 (TP) receptor [54]. 8-iso-PGF2α has been found to elicit airway hyper-responsiveness in isolated perfused mouse lungs, and cause airway obstruction and air plasma exudation in guinea pigs in *vivo* [55]. These experimental findings offerassumption about the contribution of Isoprostanes to the airway narrowing that is characteristic of asthma and in addition to being reliable signaling marker of lipid peroxidation, Isoprostane may prove to have an important biological role in the pathological of asthma. A significant elevation of reactive oxygen species, MDA formation (A product of Lipid peroxidation) and Isoprotane was estimated in the broncho-alveolar lavage (BAL) fluidwithin 24 hrs of allergeninduced asthma. This clearly indicates, Isoprotane is produce as a biomarker in respiratory tract tissues that leads to the late observed physical symptoms in allergeninduced asthma [56].

A recent study demonstrated that concentrations of exhaled ethane were increased in patients with more severe bronchoconstriction (forced expiratory volume in one second (FEV1) <60%), compared with less-constricted patients (FEV1 > 60%) and provides evidence that lipid peroxidation is related to asthma severity. These relationships between markers of oxidative stress and disease severity suggest that such tests may indicate the clinical status of asthma patients [57]. The increased level of 8-sio-PGF2α concentrations has been observed in chronic obstructive pulmonary diseases and asthma [58]. The discovery of Isoprostane has generated attention, as they provide a reliable index of oxidative stress *in vivo*. Isoprostane are structurally stable, are produced *in vivo* and are present in relatively high concentrations [59]. Traceable levels of F2-isoprostanes can be found in all normal animal and

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

**Figure 3.**

*Lipid peroxidation metabolites as influential signaling biomarkers in lung diseases.*

human biological fluids (including plasma, urine, bile, gastric juice, synovial fluid and cerebrospinal fluid)), and esterified in normal animal tissues. Thus, they overcome many of the methodological problems associated with other signaling markers. Determination of 8-iso-PGF2αas a marker of oxidative stress, of carbon tetrachloride (CCl4)-induced lipid peroxidation has been shown to be 20 times more sensitive than measurement of Thiobarbituric acid reactive substances (TBARS). Thus, the reliability of isoprostanes as in vivo markers of lipid peroxidation makes them an extremely valuable signaling biomarker for defining the potential of antioxidant agents (Vitamin C, E and β-carotene) in humans [60]. A significant amount of elevated ethane produced following lipid peroxidation has been observed in plasma and breath condensate of asthmatics as a biomarker indicator of acute airway inflammatory diseases. Moreover, measurement of auto-antibodies directed against oxidative modifications of low density lipids (LDL) is a recently developed technique that provides an in vivo marker of lipid peroxidation. Enzymes-linked immunosorbent assays are available in kit form, providing a quick and simple methodology. Thus measurement of isoprostanes in breath condensate should provide useful information concerning the degree of oxidant stress and success of antioxidant therapy in asthma (**Figure 3**).

#### **5. Lipid peroxidation: a signaling mechanism in diagnosis of liver injury**

Oxidative stress is one of the mechanisms involved in the pathogenesis of drug-induced reactive oxygen species which lead to the depletion of intracellular antioxidants, causing an imbalance in the redox status of the hepatic cells [61]. Rapid, extensive lipid peroxidation of the membrane structural lipids due to oxidative stress mechanism involved in the pathogenesis of drug-induced had seen proposed as the basis of drug-induced hepatocellular toxicity. The most of the xenobiotics such as Acetaminophen, Isoniazid and Rifampicin are well-known to

#### *Accenting Lipid Peroxidation*

induced hepatic damage directly or indirectly via lipid peroxidation [62]. However, peroxy radical attribute to lipid peroxidation, thus known for the destabilization and disintegration of the cell membrane, that further causes arteriosclerosis, hepatic and kidney damage. The increased serum markers such as MDA formation are of diagnostic importance of hepatic injury because they are released due to the damage of hepatocytes and consequently participate in endogenous enzymatic antioxidant system imbalance [63]. CCl4-ehanced lipid peroxidation has been observed in liver tissue homogenates, isolated hepatocytes and in vivo, and this has been associated with changes in endoplasmic reticular enzyme activity, in vivo fatty acid export and protein synthesis [64]. CCL4 metabolism enhances production of malondialdehyde in vitro and increase ethane production and lethality in vivo (**Figure 4**). Consequently, lipid peroxidation initiated by free radical reactions and unchecked by compromised cellular defenses, provides a possible link between

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

ethanol metabolism and associated liver disease [65]. The lipid peroxide content of liver is elevated by both short and long-term ethanol exposure and an enhanced rate of lipid peroxide formation following ingestion has been ascertained by MDA production, diene conjugate formation and *in vivo* ethane and pentane exhalation. Lipid peroxidation might merely be a sign of oxidative processes which occur after reduced glutathione is depleted concomitant with free radical attack on cellular protein and nucleic acid. The elevated MDA formation as a product of lipid peroxidation in drug-induced liver damage provide a significant biological signaling marker for the early detection or diagnosis of liver injury.
