Toxic effects of AB-CHMINACA on liver and kidney and detection of its blood level in adult male mice

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.