Compose The GPX Mimic Se-Hyaluronic Acid And Study On Its Antixoidant Activity

Reactive oxygen species (ROS) are products of the normal metabolicactivities of aerobicliving organism and are produced in response to variousstimuli.Under normal conditions, there is a balance between the production ofROS and their destruction.In certain pathogenic states the production of ROS isenhanced and the excess ROS damage biomacromolecules such as RNA, DNA,protein, sugars and lipids, and this results in ROS-mediated diseases.ROSrelated-diseases include reperfusion injury, inflammatory process, age-relateddiseases, neuronalapoptosis, cancer and cataract. In order to scavenge the ROS,the living organism has sever allines of defense system, including enzymatic andnon-enzymatic action.GPX react very important role in the metabolic activitiesof ROS, it can eliminate H2O2 and ROOH.A lot of evidence demonstrate thatthe ability of GPX to eliminate H2O2 is much stronger than CAT and others.Dueto the limitations associated with native GPX (solution instability, limitedcellular accessibility, immunogenicity, short half-lives, costs of production, andproteolyticdigestion).Scientists have made a great deal of efforts to study thestructure-activity correlation of native GPX, prepared many GPX mimics andstudied the biological effects of GPX mimics.At present, some GPX mimics have been devised, such as Ebselen ,Desferal-Mn and 2-selenium of cyclodextrin .Ebselen is a well-known GPXmimic, but its GPX activity is only about 1 U/μmol.Due to only considerationof chemic al property not consideration of catalytic mechanism and function ofenzyme, most mimics have very low GPX activity.Basing on the framework of hyaluronic acid(HA) and method of chemicalmodification, a novel selenide hyaluronic acid (SeHA) was synthesized to befunctioned as a mimic of glutathione peroxidase (GPX) .The structure of SeHAwas characterized by means of IR and NMR with the conclusion that the targetSeH was located at –CH2OH of the N-acetyl-D-glucosamine.The GPXactivities of SeHA was determined to be 276 U/μmol, which is 278 times higherthan that of Ebselen, respectively.SeHA exhibits the highest GPX activityamong the reported small GPX mimics.Because of some advantages of SeHA(high GPX activity, good water solubility, low cost of production, sugarbackbone and so on) , it has great potential in antioxidant drug.Antioxidant activity was studied by using two different model system:ferrous sulfate/ ascorbate-induced mitochondria damage model system and H2O2induced erythrocytes hemolysis and Hydroper-Oxidation model system.Theresult demonstrated that SeHA not only could inhibited the swelling ofmitochondria,reduced the accumulation of MDA,preserved the activity ofcytochrome-coxidase in the mitochondria damage model system, and comparedwith Ebselen, SeHA exhibited more stronger ability to protect the damagedmitochondria.In the H2O2 induced erythrocytes hemolysis and Hydroper-Oxidation model system, SeHA had obvious protection to restrain thehemolysis of erythrocytes,avoid the decrease of hemoglobin,inhibite the lipidperoxidation of damage erythrocytes.The ability of SeHA to protect vivalagainst oxidative damage is obviously stronger than other antioxidants, such asEbselen,GSH.These result demonstrate that, as a kind of new GPX mimic,SeHA will react very important role in the ROS-mediated diseases therapy.