Dehyde, F2-isoprostane, HNE, acrolein and Ox-LDL), oxidized proteins (protein carbonyl and protein nitrotyrosine), DNA oxidation (8-OHdG), nitric oxide and antioxidant enzymes (SOD, CAT, GPx, GR and total antioxidant capacity [17,44,45].Biomarkers of lipid damageMalonaldehydeLipids are susceptible targets of oxidation, and lipid peroxidation products are potential biomarkers for oxidative stress status in SLE [34,81]. Lipid peroxidation generates a variety of relatively stable decomposition end products, mainly unsaturated reactive aldehydes, such as MDA, Hexanoyl-Lys adduct (HEL), HNE and 2-propenal (acrolein) [82], and isoprostanes [83], which can be measured in various biological samples (serum/plasma and urine) as an indirect index of oxidative stress. Three of the most well studied markers of lipid peroxidation are MDA, HNE and 8-isoPGF2 in SLE patients and animal models, though some others lipid peroxidation markers (acrolein, OxLDL, oxidized phospholipid/apolipoprotein-B) have been RG7800 biological activity reported in few studies [15,18].MDA is generated in vivo by peroxidation of polyunsatuated fatty acids and represent a stable end product of lipid peroxidation. It is an extensively studied biomarker of lipid peroxidation in SLE patients and animal models due to the simple method of detection. MDA is typically quantified from various blood compartments (plasma, serum, lymphocytes) and tissue PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25112874 using a colorimetric assay based on the reaction between MDA and thiobarbituric acid (TBA). This is simple and is the most frequently used method in lipid peroxidation research, but other (aldehydes) compounds also react with TBA to form color that can interfere with this assay. Other more sensitive methods like HPLC, LC-MS and MS-MS can separate MDA from other aldehydes and this is suggested as a sensitive technique for measuring levels of MDA in various biological fluids in SLE patients, though some scientists question its clinical utility. Recently, a high sensitive ELISA method has been developed for measuring MDA levels in serum/ plasma or other biological fluids. This antibody based method is typically validated against the measurement of MDA by HPLC and it demonstrates better performance with improved specificity [84]. Increased levels of MDA have been associated with many clinical features like lupus nephritis and tissue damage in SLE [14,25]. Several groupsShah et al. Journal of Biomedical Science 2014, 21:23 http://www.jbiomedsci.com/content/21/1/Page 8 ofFigure 3 Formation of oxidative modified biomarkers by reactive oxygen species. Lipid peroxidation biomarkers: malondialdehyde, F2-isoprostane, acrolein and Ox-LDL. Protein oxidation markers: protein carbonyl and protein nitration. Oxidative DNA damage biomarkers: 8-hydroxy-2-deoxyguanosine (8-OHdG). Antioxidant enzymes and molecules: superoxide dismutase, catalase, glutathione peroxidase, oxidized glutathione, total antioxidant capacity.have shown an increased level of MDA and its association with nephritis and CVD in SLE patients [14,25,26]. The clinical trials attempting to replenish intracellular glutathione using N-acetyl cysteine (NAC) (24 SLE patients, Perl group and 40 SLE patients, Tewthanom group) have shown to reduce MDA levels and lupus nephritis [24,35]. These studies suggest a potential role of lipid oxidation in prediction the progression of nephritis and response to therapy. However, the mechanism of the action of NAC is currently under investigation and further studies are required to de.
