title: CCl4 induces tissue-type plasminogen activator in rat brain; protective effects of oregano, rosemary or vitamin E.
abstract: The high metabolic rate and relatively low antioxidant defenses of the lipid-rich brain tissue render it highly susceptible to reactive oxygen species (ROS) and oxidative stress, whereas the implication of ROS in the pathogenesis of several diseases in the central nervous system is well-established. The plasminogen activator (PA) system is a key modulator of extracellular proteolysis, extracellular matrix remodeling and neuronal cell signaling and has been implicated in the pathogenesis of these diseases. This study evaluates the role of tissue-type PA (t-PA) in oxidative stress and the protective role of dietary antioxidants in the rat brain. We used the CCl4 experimental model of ROS-induced lipid peroxidation and evaluated the antioxidant effect of oregano, rosemary or vitamin E. CCl4-treated Wistar rats exhibited elevated brain t-PA activity, which was decreased upon long-term administration of oregano, rosemary or vitamin E. PA inhibitor-1 (PAI-1) activity was also slightly elevated by CCl4, but this increase was not affected by the antioxidants. We hypothesize that the CCl4-induced t-PA activity indicates extracellular proteolytic activity that may be linked to neuronal cell death and brain damage. Vitamin E or antioxidants present in oregano or rosemary are effective in inhibiting t-PA elevation and can be considered as a potential protection against neuronal damage.
authors.affiliation: Department of Animal Structure and Function, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. Electronic address: slavrent@vet.auth.gr.
authors.forename: Sophia N
authors.initials: SN
authors.lastname: Lavrentiadou
authors.forename: Maria P
authors.initials: MP
authors.lastname: Tsantarliotou
authors.forename: Ioannis A
authors.initials: IA
authors.lastname: Zervos
authors.forename: Efstathios
authors.initials: E
authors.lastname: Nikolaidis
authors.forename: Marios P
authors.initials: MP
authors.lastname: Georgiadis
authors.forename: Ioannis A
authors.initials: IA
authors.lastname: Taitzoglou
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000633:toxicity*; D019587:Dietary Supplements; D008297:Male; D031341:Origanum; D018384:Oxidative Stress / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D027542:Rosmarinus; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D020011:Protective Agents; D014810:Vitamin E; D002251:Carbon Tetrachloride; D010959:Tissue Plasminogen Activator
keywords: Brain; CCl(4)-toxicity; Culinary plants; Dietary antioxidants; Plasminogen activators; Rat