Toxic effects of xylazine on endothelial cells in combination with cocaine and 6-monoacetylmorphine

Silva-Torres, Luz; Vélez, Christian; Alvarez, Juan; Ortíz, José G.; Zayas, Beatriz

doi:10.1016/j.tiv.2014.06.013

Cited by 10 publications

(7 citation statements)

References 68 publications

(73 reference statements)

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“…The results of the experiment corroborate those of other studies which showed that xylazine is toxic to thymocytes (CUPIĆ et al, 2003), splenocytes (CUPIĆ et al, 2001), chondrocytes (MANCINI et al, 2017), mesenchymal cells (EDMONDS et al, 2016) and endothelial cells (SILVA-TORRES et al, 2014). Mancini et al (2017) assessed the cell morphology of chondrocytes treated with xylazine using cell cytometry and verified cell death due to apoptosis.…”

Section: Resultssupporting

confidence: 85%

Evaluation of the effects of acepromazine and xylazineon viability in an equine dermal cell line

Silveira

Cappelari

Varela

et al. 2020

AVB

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Xylazine and acepromazine are drugs used exclusively in veterinary medicine. Xylazineis used as a sedative, analgesic, and tranquilizer while acepromazine is used as a sedative, pre-anesthetic, and anesthetic adjuvant. In vitrodrug toxicity experimentation is essential to predict possible damage associated with treatment. This study was carried out to evaluate and compare the in vitroeffects of acepromazine and xylazine on cell viability. Equine Dermis cells lines were used to examine different drug concentrations (0.02 mg/mL, 0.01 mg/mL, 0.005 mg/mL and 0.0025 mg/mL). An MTT assay was carried out to reveal cell viability. Both tested drugs reduced the viability of ED cells at 0.02 and 0.01 mg/mL. At 0.005 mg/mL, only acepromazine presented an effect. These results corroborate previous studies with xylazine. On the other hand, this is thefirst report about acepromazine and cell viability. Previous studies suggest that the mechanisms involved in reducing cell viability are apoptosis for xylazine and the activation of the autophagic pathway for acepromazine. Both mechanisms have been seen in other drugs of the same classes. These findings reveal that both acepromazine and xylazine cause concentration-dependent cytotoxicity in vitro. Future experiments could further elucidate the mechanisms by which this effect happens and thus circumvent therisk of potential tissue damage in vivo.

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Section: Resultssupporting

confidence: 85%

Evaluation of the effects of acepromazine and xylazineon viability in an equine dermal cell line

Silveira

Cappelari

Varela

et al. 2020

AVB

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“… 15 However, the toxic effects of xylazine in combination with heroin and/or cocaine or other drugs in humans have remained unexplored due to the restriction of its administration to humans. 15 , 16 …”

Section: Introductionmentioning

confidence: 99%

“…The effects of xylazine could be attenuated, blocked, and reversed with the α2-adrenergic antagonist yohimbine . In the past decade, xylazine became a popular recreational drug worldwide , and has been widely used to adulterate illicit drugs such as cocaine, heroin, and speedball (a mixture of cocaine and heroin) . However, the toxic effects of xylazine in combination with heroin and/or cocaine or other drugs in humans have remained unexplored due to the restriction of its administration to humans. , …”

Section: Introductionmentioning

confidence: 99%

“…13 In the past decade, xylazine became a popular recreational drug worldwide 3,14 and has been widely used to adulterate illicit drugs such as cocaine, heroin, and speedball (a mixture of cocaine and heroin). 15 However, the toxic effects of xylazine in combination with heroin and/or cocaine or other drugs in humans have remained unexplored due to the restriction of its administration to humans. 15 The analytical techniques to determine xylazine proposed in the literature have included high-performance liquid chromatography with ultraviolet absorbance detection, 17 gas chromatography coupled with mass spectrometry, 6 and liquid chromatography with mass spectrometry.…”

Section: ■ Introductionmentioning

confidence: 99%

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Nanocoral-like Polyaniline-Modified Graphene-Based Electrochemical Paper-Based Analytical Device for a Portable Electrochemical Sensor for Xylazine Detection

et al. 2022

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A portable electrochemical device for xylazine detection is presented for the first time. An electrochemical paper-based analytical device (ePAD) was integrated with a smartphone. The fabrication of the ePAD involved wax printing, low-tack transfer tape, and cutting and screen-printing techniques. Graphene ink was coated on the substrate and modified with nanocoral-like polyaniline, providing an electron transfer medium with a larger effective surface area that promoted charge transfer. The conductive ink on the ePAD presented a thickness of 25.0 ± 0.9 μm for an effective surface area of 0.374 cm 2 . This sensor was then tested directly on xylazine using differential pulse voltammetry. Two linear responses were obtained: from 0.2 to 5 μg mL –1 and from 5 to 100 μg mL –1 . The detection limit was 0.06 μg mL –1 . Reproducibility was tested on 10 preparations. The relative standard deviation was less than 5%. The applicability of the sensor was evaluated with beverage samples spiked with trace xylazine. Recoveries ranged from 84 ± 4 to 105 ± 2%. The developed sensor demonstrated excellent accuracy in the detection of trace xylazine. It would be possible to develop the portable system to detect various illicit drugs to aid forensic investigations.

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“…Our previous study demonstrated XYL use alone or in combination with COC and/or 6-MAM diminished proliferation and induced apoptosis in EA.hy926 cells (HUVEC) [ 25 ]. This apoptosis process could be triggered by increased production of nitrogen and oxygen reactive species.…”

Section: Introductionmentioning

confidence: 99%

Xylazine as a Drug of Abuse and Its Effects on the Generation of Reactive Species and DNA Damage on Human Umbilical Vein Endothelial Cells

Silva-Torres

Vélez

Álvarez

et al. 2014

Journal of Toxicology

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Human xylazine (XYL) abuse among addicts has received great interest due to its potential toxic effects upon addicts and the need to understand the mechanism of action associated with the potential health effects. XYL is an alpha-2 agonist restricted to veterinarian applications, without human medical applications. Our previous work demonstrated that XYL and its combination with cocaine (COC) and/or 6-monoacetylmorphine (6-MAM) induce cell death through an apoptotic mechanism. The aim of this study was to determine the effect of xylazine on the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) as well as DNA damage on endothelial cell. Human umbilical vein endothelial cells (HUVEC) were treated with XYL (60 μM), COC (160 μM), 6-MAM (160 μM), camptothecin (positive control, 50 μM), XYL/COC (50 μM), XYL/6-MAM (50 μM), and XYL/COC/6-MAM (40 μM) for a period of 24 hours. Generation of intracellular ROS, RNS, and DNA fragmentation were analyzed using a fluorometric assay. Results reveal that XYL and 6-MAM increase levels of ROS; no induction of RNS production was observed. The combination of these drugs shows significant increase in DNA fragmentation in G2/M phase, while XYL, COC, and 6-MAM, without combination, present higher DNA fragmentation in G0/G1 phase. These findings support that these drugs and their combination alter important biochemical events aligned with an apoptotic mechanism of action in HUVEC.

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Toxic effects of xylazine on endothelial cells in combination with cocaine and 6-monoacetylmorphine

Cited by 10 publications

References 68 publications

Evaluation of the effects of acepromazine and xylazineon viability in an equine dermal cell line

Evaluation of the effects of acepromazine and xylazineon viability in an equine dermal cell line

Nanocoral-like Polyaniline-Modified Graphene-Based Electrochemical Paper-Based Analytical Device for a Portable Electrochemical Sensor for Xylazine Detection

Xylazine as a Drug of Abuse and Its Effects on the Generation of Reactive Species and DNA Damage on Human Umbilical Vein Endothelial Cells

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