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,4-dihydroxynonane-mercapturic Acid

4-Hydroxy-2-nonenal (HNE) is a major product of the lipid peroxidation process that is a consequence of free radical reactions. An enzyme immunoassay (EIA) of the major urinary metabolite of HNE, i.e. 1,4-dihydroxynonane-mercapturic acid (DHN-MA) enables direct measurement of DHN-MA in urine with good sensitivity and specificity. Cross-reactivity is very low with 1,4-dihydroxynonene and with different mercapturic acids except with one other HNE urinary metabolite. Good correlation is obtained between EIA and liquid LC/MS quantitation when analyzing urine samples with different oxidative status.

Oxidized Phospholipids

Phospholipids (PLs) are a major class of polar lipids that are abundantly present within cell membranes and the outer shell of lipoprotein particles. Oxidized phospholipids (OxPLs) are generated from (poly)unsaturated diacyl- and alk(en)ylacyl glyc- erophospholipids under conditions of oxidative stress. OxPLs exert a wide variety of biological effects on diverse cell types in vitro as well as in vivo and are responsible for the pathophysiological actions of oxidized low-density lipoproteins. OxPLs play a role in the development of several chronic diseases and there is growing interest in their potential use as biomarkers of human diseases listed in Table 5.2.

The most sensitive and powerful method for OxPL analysis is mass spectrometry (MS). Development of electrospray ionization MS (ESI-MS) or atmospheric pressure chemical ionization MS (APCI-MS) has enabled sensitive and efficient metabolic profiling of lipids present in a variety of biological samples (tissues and fluids) including atherosclerotic plaque, brain, plasma and cerebrospinal fluid (Philippova et al. 2014). However, large-scale MS analysis of clinical samples remains a challenge due to the complexity and high costs of the technique. The bulk of existing clinical data on OxPL levels in human disease has been obtained using immunological methods. Use of MAbs for detection of various types of OxPLs as well as better characterization of their target oxidation-specific epitopes by mass spectrometry analysis of the spectrum would help to overcome the limitations of current OxPL detection methods.

Table 5.2 Oxidized phospholipids as biomarkers of various diseases

Cardiovascular diseases

Atherosclerosis

Hypercholesterolemia treated with statins Coronary artery disease Myocardial infarction

Diabetes and metabolic syndrome

Diabetes with cardiovascular disease Diabetic nephropathy

Chronic renal disease

Renal insufficiency patients on dialysis

Neurological disorders

Schizophrenia Bipolar disorder Neurodegenerative diseases Chemotherapy-induced neurological disorders

Pulmonary disorders

Lung injury

Cancer

Bilary strictures due to cholangiocarcinoma and pancreatic cancer

Leprosy: disseminated form

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