title: Oxidation inhibits iron-induced blood coagulation.
abstract: Blood coagulation under physiological conditions is activated by thrombin, which converts soluble plasma fibrinogen (FBG) into an insoluble clot. The structure of the enzymatically-generated clot is very characteristic being composed of thick fibrin fibers susceptible to the fibrinolytic degradation. However, in chronic degenerative diseases, such as atherosclerosis, diabetes mellitus, cancer, and neurological disorders, fibrin clots are very different forming dense matted deposits (DMD) that are not effectively removed and thus create a condition known as thrombosis. We have recently shown that trivalent iron (ferric ions) generates hydroxyl radicals, which subsequently convert FBG into abnormal fibrin clots in the form of DMDs. A characteristic feature of DMDs is their remarkable and permanent resistance to the enzymatic degradation. Therefore, in order to prevent thrombotic incidences in the degenerative diseases it is essential to inhibit the iron-induced generation of hydroxyl radicals. This can be achieved by the pretreatment with a direct free radical scavenger (e.g. salicylate), and as shown in this paper by the treatment with oxidizing agents such as hydrogen peroxide, methylene blue, and sodium selenite. Although the actual mechanism of this phenomenon is not yet known, it is possible that hydroxyl radicals are neutralized by their conversion to the molecular oxygen and water, thus inhibiting the formation of dense matted fibrin deposits in human blood.
authors.affiliation: Department of Physiology, Faculty of Health Sciences, University of Pretoria, Private Bag x323, Arcadia 0007, South Africa. resia.pretorius@up.ac.za
authors.forename: Etheresia
authors.initials: E
authors.lastname: Pretorius
authors.forename: Janette
authors.initials: J
authors.lastname: Bester
authors.forename: Natasha
authors.initials: N
authors.lastname: Vermeulen
authors.forename: Boguslaw
authors.initials: B
authors.lastname: Lipinski
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology*; D005260:Female; D005290:Ferric Compounds / Q000494:pharmacology*; D005337:Fibrin / Q000737:chemistry* / Q000648:ultrastructure; D005340:Fibrinogen / Q000737:chemistry* / Q000648:ultrastructure; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors*; D008751:Methylene Blue / Q000494:pharmacology; D008855:Microscopy, Electron, Scanning; D016877:Oxidants / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018038:Sodium Selenite / Q000494:pharmacology; D013927:Thrombosis / Q000097:blood / Q000517:prevention & control; D055815:Young Adult
chemical_list: D002712:Chlorides; D005290:Ferric Compounds; D016877:Oxidants; D017665:Hydroxyl Radical; D005337:Fibrin; D005340:Fibrinogen; D006861:Hydrogen Peroxide; D018038:Sodium Selenite; D008751:Methylene Blue; C024555:ferric chloride