Abstract
Abstract
Background
AB-CHMINACA is a cannabimimetic indazole derivative. In 2013, it was reported in different countries as a substance of abuse.
Purpose
This study evaluated the subacute toxic effects of AB-CHMINACA on the liver and kidneys and measured its blood level in adult male mice.
Methods
The histological and biochemical subacute toxic effects on the liver and kidneys were assessed after four weeks of daily intraperitoneal injections of one of the following doses: 0.3 mg/kg, 3 mg/kg, or 10 mg/kg as the highest dose in adult male albino mice. In addition, the blood concentration level of AB-CHMINACA was determined by GC–MS-MS.
Results
The histological effects showed congestion, hemorrhage, degeneration, and cellular infiltration of the liver and kidney tissues. Considering the control groups as a reference, biochemical results indicated a significant increase in the serum AST only in the highest dose group, while the ALT and creatinine levels did not significantly change. The mean values of AB-CHMINACA blood levels were 3.05 ± 1.16, 15.08 ± 4.30, and 54.43 ± 8.70 ng/mL for the three treated groups, respectively, one hour after the last dose of intraperitoneal injection. The calibration curves were linear in the 2.5–500 ng/mL concentration range. The intra-assay precision and accuracy of the method were less than 7.0% (RSD) and ± 9.2% (Bias).
Conclusion
This research supports the available case reports on AB-CHMINACA toxicity that it has low lethality; still, the chronic administration causes evident liver and kidney histotoxic effects even at low doses with unnoticeable clinical effects in mice.
Publisher
Springer Science and Business Media LLC
Subject
Biochemistry (medical),Toxicology,Pathology and Forensic Medicine
Reference51 articles.
1. Longworth M, Banister SD, Mack JBC, Glass M, Connor M, Kassiou M (2016) The 2-alkyl-2H-indazole regioisomers of synthetic cannabinoids AB-CHMINACA, AB-FUBINACA, AB-PINACA, and 5F-AB-PINACA are possible manufacturing impurities with cannabimimetic activities. Forensic Toxicol 34:286–303. https://doi.org/10.1007/s11419-016-0316-y
2. Uchiyama N, Shimokawa Y, Kawamura M, Kikura-Hanajiri R, Hakamatsuka T (2014) Chemical analysis of a benzofuran derivative, 2-(2-ethylaminopropyl) benzofuran (2-EAPB), eight synthetic cannabinoids, five cathinone derivatives, and five other designer drugs newly detected in illegal products. Forensic Toxicol 32:266–281. https://doi.org/10.1007/s11419-014-0238-5
3. Hudson S, Ramsey J (2011) The emergence and analysis of synthetic cannabinoids. Drug Test Anal 3:466–478. https://doi.org/10.1002/dta.268
4. Wiley JL, Marusich JA, Lefever TW, Antonazzo KR, Wallgren MT, Cortes RA, Patel PR, Grabenauer M, Moore KN, Thomas BF (2015) AB-CHMINACA, AB-PINACA, and FUBIMINA: affinity and potency of novel synthetic cannabinoids in producing Δ9-Tetrahydrocannabinol-like effects in mice. J Pharmacol Exp Ther 354:328–339. https://doi.org/10.1124/jpet.115.225326
5. Solimini R, Busardo FP, Rotolo MC, Ricci S, Mastrobattista L, Mortali C, Graziano S, Pellegrini M, Di Luca NM, Palmi I (2017) Hepatotoxicity associated to synthetic cannabinoids use. Eur Rev Med Pharmacol Sci 21:1–6
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献