Effect of Methamphetamine Exposure on the Plasma Levels of Endothelial-Derived Microparticles Publisher Pubmed



Nazari A¹ ; Zahmatkesh M^{1, 2} ; Mortaz E^{3, 4, 5} ; Hosseinzadeh S⁶
Source: Drug and Alcohol Dependence Published:2018

Abstract

Background: Methamphetamine (Meth), a neurotoxin, induces inflammation, oxidative stress, and triggers endothelial dysfunction and cardiovascular disease which is the second cause of death among individuals with Meth-use disorder. Oxidative stress and inflammation trigger the microparticle (MP) release. These are extracellular vesicles extracted from cell surface and identified in biological fluids. MP levels alter during pathological conditions, suggesting its potential biomarker role. In this respect, we designed the present experiment to investigate the effects of Meth on the plasma level of the endothelial-derived microparticle (EMP). Methods: Animals received Meth (4 mg/kg i.p.) for 1, 7 and 14 days and then, the plasma level of EMPs was evaluated, using cell surface markers, including AnnexinV, CD144, CD31, CD41a antigens with the flow cytometry method. The biochemical indices and locomotor activity were also assessed in a rat model. Results: Meth increased locomotor activity (Meth-1, 277.12 ± 20.17; Meth-7, 262.25 ± 11.95; Meth-14, 265.75 ± 14.75), inflammatory and oxidative indices as evidenced by rising of the C-reactive protein (Meth-7, 39.4 ± 1.24; Meth-14, 38.58 ± 2.19, vs 8.65 ± 0.45, mg/L) and malondialdehyde (Meth-7, 9.74 ± 1.38; Meth-14, 14.6 ± 1.45, vs 4.43 ± 0.32 nmol/L) plasma levels. We also found that Meth triggered endothelial injury, as demonstrated by elevated levels of EMP (Meth-7, 4.77 ± 0.22; Meth-14, 5.91 ± 0.34, % total events/mL) compared with control group. Conclusion: Our data showed that Meth exposure stimulates inflammatory and oxidative pathways and facilitates the EMPs shedding. Measuring the level of EMPs might be applied as a potential diagnostic index to monitor the endothelial dysfunction in substance-use disorders. © 2018 Elsevier B.V.