title: Toxic effects of xylazine on endothelial cells in combination with cocaine and 6-monoacetylmorphine.
abstract: The use of xylazine as a drug of abuse has emerged worldwide in the last 7 years, including Puerto Rico. Clinical findings reported that xylazine users present greater physiological deterioration, than heroin users. The aim of this study was to assess the xylazine toxicity on endothelial cells, as this is one of the first tissues impact upon administration. Human umbilical vein endothelial cells in culture were treated with xylazine, cocaine, 6-monoacetylmorphine (heroin metabolite) and its combinations, at concentrations of 0.10-400 μM, for periods of 24, 48 and 72 h. IC50 were calculated and the Annexin V assay implemented to determine the cell death mechanism. Results indicated IC50 values at 24h as follow: xylazine 62 μM, cocaine 210 μM, 6-monoacetylmorphine 300 μM. When these drugs were combined the IC50 value was 57 μM. Annexin V results indicated cell death by an apoptosis mechanism in cells treated with xylazine or in combination. Results demonstrated that xylazine use inhibits the endothelial cell proliferation, at lower concentrations than cocaine and 6-monoacetylmorphine. These findings contribute to the understanding of the toxicity mechanisms induced by xylazine on endothelial cells.
authors.affiliation: University of Puerto Rico, Pharmacology and Toxicology Department, School of Medicine, Medical Science Campus, Puerto Rico; Puerto Rico Institute of Forensic Science, San Juan, Puerto Rico. Electronic address: luz.silva@upr.edu.
authors.forename: L A
authors.initials: LA
authors.lastname: Silva-Torres
authors.affiliation: Universidad Metropolitana, School of Environmental Affairs, San Juan, Puerto Rico.
authors.forename: C
authors.initials: C
authors.lastname: Vélez
authors.affiliation: Puerto Rico Institute of Forensic Science, San Juan, Puerto Rico; University of Puerto Rico, School of Health Professions, Medical Science Campus, Puerto Rico.
authors.forename: J
authors.initials: J
authors.lastname: Lyvia Alvarez
authors.affiliation: University of Puerto Rico, Pharmacology and Toxicology Department, School of Medicine, Medical Science Campus, Puerto Rico.
authors.forename: J G
authors.initials: JG
authors.lastname: Ortiz
authors.affiliation: University of Puerto Rico, Pharmacology and Toxicology Department, School of Medicine, Medical Science Campus, Puerto Rico; Universidad Metropolitana, School of Environmental Affairs, San Juan, Puerto Rico.
authors.forename: B
authors.initials: B
authors.lastname: Zayas
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003042:Cocaine / Q000633:toxicity*; D004347:Drug Interactions; D042783:Endothelial Cells / Q000187:drug effects*; D006801:Humans; D009022:Morphine Derivatives / Q000633:toxicity*; D014991:Xylazine / Q000633:toxicity*
chemical_list: D009022:Morphine Derivatives; D014991:Xylazine; D003042:Cocaine; C026979:6-O-monoacetylmorphine
keywords: 6-Monoacetylmorphine; Apoptosis; Cocaine; Drug abuse; Xylazine