The assessment of in vitro cardiotoxic potentials for synthetic cannabinoid, AM-2201

Yıl 2019, Cilt: 49 Sayı: 3, 121 - 124, 01.12.2019

Esra Nişikli Müzeyyen Çeliksöz Akar Gül Özhan

Öz

DOI: 10.26650/IstanbulJPharm.2019.19004

Synthetic cannabinoid abuse becomes more common in recent years, although knowledge about the risk of the relatively new synthetic cannabinoid molecules is not adequate. Data is mainly limited with new analytical methods and case reports related to their clinical effects. The studies are generally related to the cardiac effects of first defined molecules rather than every molecule in the group. The cardiac clinical effects of synthetic cannabinoid abuse and underlying mechanisms are not certain. Therefore, we aimed to investigate AM-2201, one of synthetic cannabinoids, because knowledge for AM-2201 is less than the others in this group. The cardiotoxicity and underlying mechanisms of AM-2201 were assessed on cardiac cell culture. The half-maximal inhibition concentration (IC50) values were 101.49 and 63.33 M by WST-1 and LDH assays. AM-2201 was not induced either the total antioxidant capacity (TAC) or reactive oxygen species (ROS) levels. As to the measurements Annexin V-FITC and acridine orange dye, AM-2201 did not induce apoptosis and the primary cell death was necrosis. According to our results, further studies such as mechanism on cell death and cancer pathways should be investigated.

You may cite this article as: Nişikli E, Çeliksöz Akar M, Özhan G (2019). The Assessment of in Vitro Cardiotoxic Potentials for Synthetic Cannabinoid, AM-2201. Istanbul J Pharm 10.26650/IstanbulJPharm.2019.19004.

Anahtar Kelimeler

AM-2201, Apoptosis, Cardiotoxicity, Cytotoxicity, Oxidative stress, Syntethic cannabinoid

Kaynakça

• Aksel G, Oner Bozan O, Kayacı M, Guneysel O, Sezgin SB, (2015). Rising threat; bonsai. Turk J Emerg Med 15: 75-78. Almada M, Costa L, Fonseca BM, Amaral C, Teixeirab N, Correia-da Silva G, (2017). The synthetic cannabinoid WIN-55,212 induced-apoptosis in cytotrophoblasts cells by a mechanism dependent on CB1 receptor. Toxicol 385: 67-73. Atik SU, Dedeoğlu R, Varol F, Çam H, Eroğlu AG, Saltık L, (2015). Cardiovascular side effects related with use of synthetic cannabinoids “bonzai”: two case reports. Turk Pediatri Ars 50(1): 61-64. Castellanos D and Gralnik LM, (2016). Synthetic cannabinoids 2015: an update for pediatricians in clinical practice. World J Clin Pediatr 5: 16-24. Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA, (2014). Synthetic cannabinoids: epidemiology, pharmacodynamics and clinical implications. Drug Alcohol Depen 144: 12-41. Cooper ZD, (2016). Adverse effects of synthetic cannabinoids: management of acute toxicity and withdrawal. Curr Psychiatry Rep 18(5): 52-71. Couceiro J, Bandarra S, Sultan H, Bell S, Constantino S, Quintas A, (2016). Toxicological impact of JWH-018 and its phase I metabolite N-(3-hydroxypentyl) on human cell lines. Forensic Sci Int 264: 100-105. Debruyne D and Boisselier RL, (2015). Emerging drugs of abuse: current perspectives on synthetic cannabinoids. Subst Abuse Rehabil 6: 113-129. Mitou G, Budak H, Gozuacik D, (2009). Techniques to study autophagy in plants. Int J Plant Genom 2015, Article ID 451357: 1-14. Gözüaçık D, (2011). Otofaji analiz yöntemleri ve uygulama aşamaları. In S. Koçtürk & H. S. Vatansever, eds. Hücre Ölümü Araştırma Teknikleri. İzmir: Dokuz Eylul University Press, 129-141. Hess C, Schoeder CT, Pillaiyar T, Madea B, Müller CE, (2016). Pharmacological evaluation of synthetic cannabinoids identified as constituents of spice. Forensic Toxicol 34: 329-343. Ibrahim S, Al-Saffar F, Wannenburg T, (2014). A unique case of cardiac arrest following K2 abuse. Case Reports in Cardiology 2014, Article ID 120607: 1-3. McKeever RG, Vearrier D, Jacobs D, LaSala GL, Okaneku J, Greenberg MI, (2015). K2-not the spice of life; synthetic cannabinoids and ST elevation myocardial infarction: A case report. J Med Toxicol 11: 129-131. Rajesh M, Mukhopadhyay P, Haskó G, Liaudet L, Mackie K, Pacher P, (2010). Cannabinoid-1 receptor activation induces reactive oxygen species-dependent and -independent mitogen-activated protein kinase activation and cell death in human coronary artery endothelial cells. Br J Pharmacol 160: 688-700. Schupp N, Schmid U, Heidland A, Stopper H, (2008). Rosuvastatin protects against oxidative stress and DNA damage in vitro via upregulation of glutathione synthesis. Atherosclerosis 199(2): 27–287. Tomiyama K and Funada M, (2011). Cytotoxicity of synthetic cannabinoids found in “Spice” products: The role of cannabinoid receptors and the caspase cascade in the NG 108-15 cell line. Toxicol Lett 207: 12-17. Tomiyama K and Funada M, (2014). Cytotoxicity of synthetic cannabinoids on primary neuronal cells of the forebrain: the involvement of cannabinoid CB1 receptors and apoptotic cell death. Toxicol Appl Pharmacol 274: 17-23. Table: The results of apoptosis and necrosis in the H9c2 cardiomyoblast cells treated with AM-2201 Concentrations (μM) Apoptosis (mean% ±standard error) Necrosis (mean% ±standard error) Negative control 0.31 ±0.03 1.03 ±0.08 12.5 0.36 ±0.04 3.94 ±0.07* 25 0.48 ±0.06 8.27 ±1.12* 50 0.76 ±0.08* 7.22 ±1.05* 100 0.94 ±0.08* 8.05 ±1.11* *p>0.05, one-way ANOVA, Post Hoc and Dunnet t-test.