ABSTRACT
Treatment of bovine pulmonary artery smooth muscle tissue mitochondria with H2O2 stimulated iron release, hydroxyl radical (OH) production and lipid peroxidation. Pretreatment of mitochondria with deferoxamine (DFO) and dimethyl thiourea (DMTU) prevented OH production and markedly reduced lipid peroxidation without appreciably altering iron release caused by H2O2. Simultaneous treatment of either DFO or DMTU with H2O2 significantly reduced lipid peroxidation and also prevented OH production without causing marked decrease in iron release. In contrast, addition of DFO or DMTU even 2 min after treatment of the mitochondria with H2O2 did not significantly altered iron release, OH production and lipid peroxidation. Pretreatment of the mitochondria with 4,4'-dithiocyano-2,2'-disulfonic acid stilbene (DIDS) markedly reduced lipid peroxidation without appreciably altering the increase in OH production and iron release caused by H2O2.
Subject(s)
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology , Animals , Cattle , Deferoxamine/pharmacology , Free Radical Scavengers/pharmacology , Hydrogen Peroxide/pharmacology , Lipid Peroxidation , Mitochondria, Muscle/drug effects , Muscle, Smooth, Vascular/drug effects , Pulmonary Circulation/drug effects , Thiourea/analogs & derivativesABSTRACT
The role of hydroxyl radical (OH.) in H2O2-mediated stimulation of lipid peroxidation in microsomes of bovine pulmonary arterial smooth muscle tissue and the protective effects of DIDS, the anion channel blocker have been studied. Treatment of microsomes with H2O2 (1 mM) stimulate iron release, OH. production and lipid peroxidation. Pretreatment with DFO (an iron chelator) or DMTU (a hydroxyl radical scavenger) prevents OH. production and thereby reduces lipid peroxidation without any appreciable reduction of iron release. Simultaneous treatment of either DFO or DMTU with H2O2 significantly reduces lipid peroxidation and prevents OH. production without any significant reduction of iron release. However, addition of DFO or DMTU 2 min after treatment of the microsome with H2O2 does not produce any significant reduction of lipid peroxidation, OH production and iron release. Pretreatment of microsomes with DIDS markedly reduces the stimulation of lipid peroxidation without appreciably altering the increase in OH. production and iron release caused by H2O2.