title: Characterization of oxidative stress in blood from diabetic vs. hypercholesterolaemic patients, using a novel synthesized marker.
abstract: In the present study, we extend our novel concept of designing and using exogenous markers for the characterization of oxidative stress (OS) and OS-associated diseases. The aim was to use such a synthetic compound as a tool for studying OS in blood from diabetic and hypercholesterolaemic (Hc) patients. The marker used N-linoleoyl tyrosine (LT) was constructed from tyrosine and linoleic acid (LA); both components are known to be easily oxidized upon exposure to different types of reactive oxygen/nitrogen species (ROS/RNS), and to generate specific oxidized products, depending on the type of oxidants present in vivo. Using the LT probe, we showed that the ratios of oxidized LT to total LT (Ox-LT/LT) is significantly higher in blood samples obtained from diabetic patients, than in Hc patients or healthy control subjects. LC/MS analysis revealed that blood from diabetic patients oxidizes the marker with predominant formation of Ox-LT hydroperoxide (LT-OOH) and epoxide (epoxy-LT), where the LA moiety is oxidized to hydroperoxide and to epoxide, respectively. Analysis of oxysterol levels in these samples (GC/MS) revealed that the blood of both diabetic and Hc patients contained significantly more oxysterols than blood of control subjects. Consumption of pomegranate juice by diabetic patients for 3 months suppressed their blood capacity to oxidize the LT and similarly also reduced their blood oxysterol/total cholesterol ratio by 93%. The use of an exogenous marker to characterize OS in blood samples yields important information on the extent of OS, and can provide a fingerprint for the early identification of different pathological conditions associated with OS.
authors.affiliation: The Laboratory of Natural Medicinal Compounds, Migal-Galilee Technology Center, Kiryat Shmona 11016, Israel.
authors.forename: Andrea
authors.initials: A
authors.lastname: Szuchman
authors.forename: Michael
authors.initials: M
authors.lastname: Aviram
authors.forename: Ramadan
authors.initials: R
authors.lastname: Musa
authors.forename: Soliman
authors.initials: S
authors.lastname: Khatib
authors.forename: Jacob
authors.initials: J
authors.lastname: Vaya
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology; D001628:Beverages; D003920:Diabetes Mellitus / Q000097:blood* / Q000503:physiopathology; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood*; D008041:Linoleic Acids; D029561:Lythraceae; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014443:Tyrosine / Q000031:analogs & derivatives*
chemical_list: D000975:Antioxidants; D008041:Linoleic Acids; C529367:N-linoleoyltyrosine; D014443:Tyrosine