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Medical Forum / General / General / August 2005Suppression of autoimmune-mediated damage
Am J Physiol Heart Circ Physiol. 2005 Aug 12; [Epub ahead of print] Related Articles, Links MCI-186 (edaravone), a Novel Free Radical Scavenger, Protects Against Acute Autoimmune Myocarditis in Rats. Nimata M, Okabe TA, Hattori M, Yuan Z, Shioji K, Kishimoto C. Department of Cardiovascular of Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Objective : In this study, we tested the hypothesis that MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one, edaravone), a novel free radical scavenger, protects against acute experimental autoimmune myocarditis (EAM) in rats by the radical scavenging action associated with the suppression of cytotoxic myocardial injury. Background : Recent evidence suggests that oxidative stress may play a role in myocarditis. Methods : We administered intraperitoneally MCI-186 1mg/kg/day, 3mg/kg/day, and 10mg/kg/day, to rats with EAM for 3 weeks. The results were compared with untreated rats with EAM. Results : MCI-186 treatment did not affect hemodynamically. MCI-186 treatment (3mg/kg/day and 10mg/kg/day) reduced the severity of myocarditis by comparing the heart weight/body weight ratio and pathologic scores. Myocardial interleukin-1beta (IL-1beta)-positive cells and myocardial oxidative stress overload with DNA damage in rats with EAM given MCI-186 treatment were significantly less compared with those of the untreated rats with EAM. In addition, MCI-186 treatment decreased not only the myocardial protein carbonyl contents but also the myocardial thiobarbituric acid reactive substance (TBARS) products in rats with EAM. The formation of hydroxyl radicals in MCI-186-treated heart homogenates was decreased compared with untreated heart homogenates. Furthermore, cytotoxic activities of lymphocytes of rats with EAM treated with MCI-186 were significantly lower compared with those of the untreated rats with EAM. Conclusion : Hydroxyl radicals may be involved in the development of myocarditis. MCI-186 protects against acute EAM in rats associated with scavenging hydroxyl free radicals, resulting in the suppression of autoimmune-mediated myocardial damage associated with reduced oxidative stress state. PMID: 16100244 [PubMed - as supplied by publisher] -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking It seems the .. mode of action .. OF .. this .. drug .. may be .. IRON .. based .. ? <<snip>> MCI-186 inhibited iron-dependent peroxidation in rat brain homogenates and mitochondrial homogenates and prevented iron-dependent peroxidative disintegration of mitochondrial membranes . <<snip>> 1: J Pharmacol Exp Ther. 1994 Mar;268(3):1597-604. Related Articles, Links Protective effects of MCI-186 on cerebral ischemia: possible involvement of free radical scavenging and antioxidant actions. Watanabe T, Yuki S, Egawa M, Nishi H. Pharmaceuticals Laboratory I, Mitsubishi Kasei Corporation, Yokohama, Japan. The anti-ischemic effects and a possible mechanism of a new antistroke agent, 3-methyl-1-phenyl-pyrazolin-5-one (MCI-186), were studied. Preischemic treatment with MCI-186 (3 mg/kg i.v.) facilitated the recovery of electrocorticographic activity and prolonged survival time in global complete ischemia of rats; MCI-186 (1 and 3 mg/kg i.v.) also mitigated dysfunction of the blood-brain barrier and energy failure in hemispheric embolization of rats. Postischemic treatment with MCI-186 (3 mg/kg i.v.) decreased cortical infarction in focal embolization of rats. MCI-186 (0.6-2.4 mM) inhibited the OH.-induced hydroxylation of salicylate (maximal inhibition, 40.2%), but at 100 microM it did not influence O2- generation. MCI-186 inhibited the formation of linoleic acid-conjugated dienes caused by OH. (IC50 = 32.0 microM). Also, concurrent administration of MCI-186 (3-100 mg/kg i.v.) ameliorated hyperglycemia, hyperlipopeoxidemia and degranulation of beta-cells in alloxan (40 mg/kg i.v.)-treated rats. In addition, MCI-186 inhibited iron-dependent peroxidation in rat brain homogenates and mitochondrial homogenates (IC50 = 15.0 and 2.3 microM, respectively) and prevented iron-dependent peroxidative disintegration of mitochondrial membranes (IC50 = 39.0 microM). These findings suggest that MCI-186 has potent anti-ischemic actions and that its mechanism may be closely associated with beneficial antioxidant activities. PMID: 8138971 [PubMed - indexed for MEDLINE] -------------------------------------------------------------------------------- Who loves ya. Tom Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com Man Is A Herbivore! http://pages.ivillage.com/ironjustice/manisaherbivore DEAD PEOPLE WALKING http://pages.ivillage.com/ironjustice/deadpeoplewalking |
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