Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Sohag University, Sohag, Egypt.
Department of Histology, Faculty of Medicine, Sohag University, Sohag, Egypt.
Forensic Toxicol. 2024 Jan;42(1):7-17. doi: 10.1007/s11419-023-00670-0. Epub 2023 Aug 13.
AB-CHMINACA is a cannabimimetic indazole derivative. In 2013, it was reported in different countries as a substance of abuse.
This study evaluated the subacute toxic effects of AB-CHMINACA on the liver and kidneys and measured its blood level in adult male mice.
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.
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).
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.
AB-CHMINACA 是一种大麻样吲哚衍生物。2013 年，它在不同国家被报道为一种滥用物质。
本研究评估 AB-CHMINACA 对成年雄性小鼠肝脏和肾脏的亚急性毒性作用，并测定其血液水平。
通过腹腔注射不同剂量（0.3mg/kg、3mg/kg 和 10mg/kg，作为最高剂量），对成年雄性白化小鼠进行为期四周的每日腹腔注射，评估其对肝脏和肾脏的组织学和生化亚急性毒性作用。此外，通过 GC-MS-MS 测定 AB-CHMINACA 的血药浓度水平。
组织学结果显示肝脏和肾脏组织充血、出血、变性和细胞浸润。与对照组相比，生化结果仅显示在最高剂量组血清 AST 显著升高，而 ALT 和肌酐水平无显著变化。腹腔注射最后一次后 1 小时，三个处理组的 AB-CHMINACA 血药浓度平均值分别为 3.05±1.16、15.08±4.30 和 54.43±8.70ng/mL。校准曲线在 2.5-500ng/mL 浓度范围内呈线性。该方法的日内精密度和准确度均小于 7.0%（RSD）和±9.2%（偏差）。
本研究支持 AB-CHMINACA 毒性的现有案例报告，即它的致死率较低；然而，即使在低剂量下，慢性给药也会导致明显的肝和肾组织毒性作用，而在小鼠中没有明显的临床作用。
