title: Protection of coronary endothelial cells from cigarette smoke-induced oxidative stress by a new Mn(II)-containing polyamine-polycarboxilate scavenger of superoxide anion.
abstract: Oxidative stress plays a major role in cardiovascular injury and dysfunction induced by cigarette smoke. Smoke-borne pro-oxidants impair endothelial function and predispose to thrombosis, inflammation and atherosclerosis. This in vitro study evaluates whether Mn(II)(4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate).2H2O (Mn(II)(Me2DO2A)), a polyamine-polycarboxilate, Mn(II)-containing O2(-) scavenger, has a direct protective action on guinea pig coronary endothelial (GPCE) cells exposed to cigarette smoke extracts (CSE). Mn(II)(Me2DO2A) (1-10μmol/l) was added to the culture medium together with CSE and maintained for 4h. In parallel experiments, the inactive congener Zn(II)(Me2DO2A), in which Zn(II) replaced the functional Mn(II) center in the same organic scaffold, was used as negative control. Mn(II)(Me2DO2A), mostly at the higher doses (5 and 10μmol/l), significantly increased GPCE cell viability (trypan blue assay), improved mitochondrial activity (MTT test, mitochondrial membrane potential Δψ), reduced cellular apoptosis (mPTP, caspase-3 activity, TUNEL assay), decreased intracellular ROS levels (H2DCFDA), lipoperoxidation (BODIPY 581/591) and decreased protein nitrosylation. Of note, Zn(II)(Me2DO2A) did not preserve cell viability. These findings suggest that Mn(II)(Me2DO2A) is a promising O2(-) scavenging compound able to protect from cigarette smoke-induced oxidative cell injury. In perspective, should its efficacy be confirmed in future in vivo studies, this molecule might represent a therapeutic or preventive drug to counteract cigarette smoke toxicity.
authors.affiliation: Department of Experimental & Clinical Biomedical Sciences "Mario Serio", Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Becatti
authors.affiliation: Department of Experimental & Clinical Medicine, Research Unit of Histology & Embryology, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Boccalini
authors.affiliation: Department of Experimental & Clinical Medicine, Research Unit of Histology & Embryology, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pini
authors.affiliation: Department of Experimental & Clinical Biomedical Sciences "Mario Serio", Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fiorillo
authors.affiliation: Department of Chemistry, University of Florence, Florence, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bencini
authors.affiliation: Department of Experimental & Clinical Medicine, Research Unit of Histology & Embryology, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Bani
authors.affiliation: Department of Experimental & Clinical Medicine, Research Unit of Histology & Embryology, Italy. Electronic address: silvia.nistri@unifi.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nistri
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects*; D013481:Superoxides / Q000378:metabolism
chemical_list: D016166:Free Radical Scavengers; D009942:Organometallic Compounds; D012906:Smoke; C551155:manganese(II) 4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate; D013481:Superoxides
keywords: Cigarette smoke; Guinea pig coronary endothelial cells; Oxidative stress; ROS scavenger; Superoxide anion