AB-CHMINACA 对成年雄性小鼠肝脏和肾脏的毒性作用及其血药浓度检测。

IF 2.8 4区 医学 Q2 TOXICOLOGY
Forensic Toxicology Pub Date : 2024-01-01 Epub Date: 2023-08-13 DOI:10.1007/s11419-023-00670-0
Soheir Ali Mohammad, Rasha Elhaddad Ali Mousa, Sahar Mohamed Gebril, Khaled Masoud Mohamed Masoud, Rania Ahmad Radwan
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引用次数: 0

摘要

背景:AB-CHMINACA是一种大麻拟物吲唑衍生物。目的:本研究评估了 AB-CHMINACA 对成年雄性小鼠肝脏和肾脏的亚急性毒性作用,并测量了其血药浓度:方法:每天腹腔注射以下剂量之一,为期四周,评估其对肝脏和肾脏的组织学和生化亚急性毒性影响:成年雄性白化小鼠的最高剂量为 0.3 毫克/千克、3 毫克/千克或 10 毫克/千克。此外,还通过气相色谱-质谱-质谱法测定了 AB-CHMINACA 的血药浓度水平:结果:组织学效应显示肝脏和肾脏组织充血、出血、变性和细胞浸润。以对照组为参照,生化结果表明,只有最高剂量组的血清谷丙转氨酶(AST)显著升高,而谷草转氨酶(ALT)和肌酐水平没有明显变化。腹腔注射最后一剂 AB-CHMINACA 1 小时后,三个治疗组的血药浓度平均值分别为 3.05 ± 1.16、15.08 ± 4.30 和 54.43 ± 8.70 纳克/毫升。校准曲线在 2.5-500 纳克/毫升浓度范围内呈线性关系。该方法的测定内精密度和准确度分别小于 7.0%(RSD)和 ± 9.2%(偏差):这项研究支持现有的 AB-CHMINACA 毒性病例报告,即它的致死率较低;但长期给药即使剂量较低,也会对小鼠的肝脏和肾脏造成明显的组织毒性影响,且临床影响不明显。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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.

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来源期刊
Forensic Toxicology
Forensic Toxicology TOXICOLOGY-
CiteScore
5.80
自引率
9.10%
发文量
40
审稿时长
3 months
期刊介绍: The journal Forensic Toxicology provides an international forum for publication of studies on toxic substances, drugs of abuse, doping agents, chemical warfare agents, and their metabolisms and analyses, which are related to laws and ethics. It includes original articles, reviews, mini-reviews, short communications, and case reports. Although a major focus of the journal is on the development or improvement of analytical methods for the above-mentioned chemicals in human matrices, appropriate studies with animal experiments are also published. Forensic Toxicology is the official publication of the Japanese Association of Forensic Toxicology (JAFT) and is the continuation of the Japanese Journal of Forensic Toxicology (ISSN 0915-9606).
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