title: Effect of tributyltin on mammalian endothelial cell integrity.
abstract: Tributyltin (TBT), is a man-made pollutants, known to accumulate along the food chain, acting as an endocrine disruptor in marine organisms, with toxic and adverse effects in many tissues including vascular system. Based on the absence of specific studies of TBT effects on endothelial cells, we aimed to evaluate the toxicity of TBT on primary culture of porcine aortic endothelial cells (pAECs), pig being an excellent model to study human cardiovascular disease. pAECs were exposed for 24h to TBT (100, 250, 500, 750 and 1000nM) showing a dose dependent decrease in cell viability through both apoptosis and necrosis. Moreover the ability of TBT (100 and 500nM) to influence endothelial gene expression was investigated at 1, 7 and 15h of treatment. Gene expression of tight junction molecules, occludin (OCLN) and tight junction protein-1 (ZO-1) was reduced while monocyte adhesion and adhesion molecules ICAM-1 and VCAM-1 (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) levels increased significantly at 1h. IL-6 and estrogen receptors 1 and 2 (ESR-1 and ESR-2) mRNAs, after a transient decrease, reached the maximum levels after 15h of exposure. Finally, we demonstrated that TBT altered endothelial functionality greatly increasing monocyte adhesion. These findings indicate that TBT deeply alters endothelial profile, disrupting their structure and interfering with their ability to interact with molecules and other cells.
authors.affiliation: Department of Veterinary Medical Sciences - DEVET, UNICENTRO - Universidade Estadual do Centro, Oeste do Paraná, Brazil. Electronic address: giu_kasecker@uol.com.br.
authors.forename: G
authors.initials: G
authors.lastname: Botelho
authors.affiliation: Department of Veterinary Medical Sciences - DIMEVET, University of Bologna, Ozzano Emilia, Bologna, Italy. Electronic address: chiara.bernardini5@unibo.it.
authors.forename: C
authors.initials: C
authors.lastname: Bernardini
authors.affiliation: Department of Veterinary Medical Sciences - DIMEVET, University of Bologna, Ozzano Emilia, Bologna, Italy. Electronic address: augusta.zannoni@unibo.it.
authors.forename: A
authors.initials: A
authors.lastname: Zannoni
authors.affiliation: Department of Veterinary Medical Sciences - DIMEVET, University of Bologna, Ozzano Emilia, Bologna, Italy. Electronic address: vittoria.ventrella@unibo.it.
authors.forename: V
authors.initials: V
authors.lastname: Ventrella
authors.affiliation: Department of Veterinary Medical Sciences - DIMEVET, University of Bologna, Ozzano Emilia, Bologna, Italy. Electronic address: marialaura.bacci@unibo.it.
authors.forename: M L
authors.initials: ML
authors.lastname: Bacci
authors.affiliation: Department of Veterinary Medical Sciences - DIMEVET, University of Bologna, Ozzano Emilia, Bologna, Italy. Electronic address: monica.forni@unibo.it.
authors.forename: M
authors.initials: M
authors.lastname: Forni
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis; D013552:Swine; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014220:Trialkyltin Compounds / Q000633:toxicity*
chemical_list: D015815:Cell Adhesion Molecules; D062725:Tight Junction Proteins; D014220:Trialkyltin Compounds; C011559:tributyltin
keywords: Adhesion molecules; Endothelial cells; Inflammation; Tight junctions; Tributyltin