title: Mechanisms of cell death induced by infusion sets leachables in in vitro experimental settings.
abstract: Leachable materials that are released from infusion sets during their use can induce local and systemic toxic effects. We studied the mechanisms and kinetics of cell death induced by infusion sets leachates in vitro using L-929 and bEnd. 3 cells. Changes in cell morphology and metabolic activity were determined using light microscopy and the MTT test, respectively. Detailed analysis of the mechanisms of cell death was performed using membrane integrity and caspases 3 and 7 activity tests, annexin V-FITC/7-AAD analysis by FACS, and DAPI nuclear staining followed by confocal microscopy. Infusion sets released toxic leachables and induced toxic effects. Latex flashball was the most toxic part of the studied infusion sets, and it potently induced cell oncosis via increased permeability of the cell membrane. Latex-induced decrease in cells metabolic activity and cell death were not accompanied by activation of caspases 3 and 7, changes in nuclear morphology, or substantial annexin V-FITC cell staining. Leachables from the tube part of the infusion sets were less toxic, and induced some biochemical changes without altering the cells morphology. Further studies are needed to reveal the in vivo toxicity of infusion sets and its correlation with the results of in vitro toxicity studies.
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors.forename: Luba
authors.initials: L
authors.lastname: Kozlovskaya
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, The Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel. Electronic address: davidst@bgu.ac.il.
authors.forename: David
authors.initials: D
authors.lastname: Stepensky
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004209:Disposable Equipment; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007262:Infusions, Intravenous / Q000295:instrumentation; D051379:Mice; D012408:Rubber / Q000633:toxicity; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; D012408:Rubber; D053148:Caspase 3; D053179:Caspase 7; C022616:thiazolyl blue
keywords: Disposable medical devices; In vitro toxicity; Infusion sets; Natural rubber latex; Oncosis