Silva-Torres L A, Vélez C, Lyvia Alvarez J, Ortiz J G, Zayas B
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.
Universidad Metropolitana, School of Environmental Affairs, San Juan, Puerto Rico.
Toxicol In Vitro. 2014 Oct;28(7):1312-9. doi: 10.1016/j.tiv.2014.06.013. Epub 2014 Jul 8.
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.
在过去7年里，包括波多黎各在内，全世界都出现了将赛拉嗪用作滥用药物的情况。临床研究结果表明，赛拉嗪使用者的生理退化程度比海洛因使用者更严重。本研究的目的是评估赛拉嗪对内皮细胞的毒性，因为内皮细胞是给药后首先受到影响的组织之一。将培养的人脐静脉内皮细胞用赛拉嗪、可卡因、6-单乙酰吗啡（海洛因代谢物）及其组合进行处理，浓度为0.10 - 400μM，处理时间为24、48和72小时。计算IC50并进行膜联蛋白V测定以确定细胞死亡机制。结果表明，24小时时的IC50值如下：赛拉嗪62μM，可卡因210μM，6-单乙酰吗啡300μM。当这些药物联合使用时，IC50值为57μM。膜联蛋白V结果表明，用赛拉嗪处理或联合处理的细胞通过凋亡机制导致细胞死亡。结果表明，与可卡因和6-单乙酰吗啡相比，赛拉嗪在更低浓度下就能抑制内皮细胞增殖。这些发现有助于理解赛拉嗪对内皮细胞诱导的毒性机制。
