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CUMYL-4CN-BINACA对雄性白化大鼠的急性和亚急性毒性作用。

Acute and subacute toxic effects of CUMYL-4CN-BINACA on male albino rats.

作者信息

Lafzi Ayşe, Yeşilyurt Fatma, Demirci Tuba, Hacımüftüoğlu Ahmet, Şişman Turgay

机构信息

Department of Criminalistics, Graduate School of Natural and Applied Science, Atatürk University, 25240, Erzurum, Turkey.

Department of Medical Pharmacology, Medicine Faculty, Atatürk University, 25240, Erzurum, Turkey.

出版信息

Forensic Toxicol. 2024 Jul;42(2):125-141. doi: 10.1007/s11419-023-00676-8. Epub 2023 Dec 15.

Abstract

PURPOSE

There is very little information about the toxicological and pathological effects of synthetic cannabinoids, which have cannabis-like properties. This study was carried out to histopathologically, hematologically, and biochemically determine the toxic effects of acute and subacute exposure to a novel synthetic cannabinoid 1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)indazole-3-carboxamide in internal organs of adult male rats.

METHODS

The cannabinoid was injected intraperitoneally at three doses (0.5, 1.0, and 2.0 mg/kg, body weight). The cannabinoid was administered to acute groups for 2 days and to subacute groups for 14 days. Observations were made for 14 days and various changes such as mortality, injury, and illness were recorded daily. Hematological and biochemical changes were evaluated and histopathological analyses in lung, liver, and kidney tissues were also performed.

RESULTS

No mortality was observed. It was observed that there were fluctuations in hematological and serum biochemical parameters. Among the oxidative stress parameters, significant decreases in superoxide dismutase, catalase levels and significant increases in lipid peroxidation levels were determined. Serious pathological changes such as necrosis, vacuolation, congestion, and fibrosis were observed in the internal organs in a dose-dependent and time-dependent manner. It was also found that the synthetic cannabinoid triggered apoptosis in the organs. The results demonstrated that the most affected organ by the cannabinoid was the kidney.

CONCLUSION

This study showed for the first time that CUMYL-4CN-BINACA adversely affects healthy male albino rats. It can be estimated that the abuse of the cannabinoid may harm human health in the same way.

摘要

目的

关于具有大麻样特性的合成大麻素的毒理学和病理学影响,目前所知甚少。本研究旨在通过组织病理学、血液学和生物化学方法,确定成年雄性大鼠急性和亚急性暴露于新型合成大麻素1-(4-氰基丁基)-N-(2-苯基丙烷-2-基)吲唑-3-甲酰胺后,其对大鼠内脏器官的毒性作用。

方法

以三种剂量(0.5、1.0和2.0毫克/千克体重)腹腔注射该大麻素。将大麻素分别给予急性组2天,亚急性组14天。观察14天,每天记录死亡率、损伤和疾病等各种变化。评估血液学和生化变化,并对肺、肝和肾组织进行组织病理学分析。

结果

未观察到死亡情况。观察到血液学和血清生化参数存在波动。在氧化应激参数中,超氧化物歧化酶、过氧化氢酶水平显著降低,脂质过氧化水平显著升高。在内脏器官中观察到坏死、空泡化、充血和纤维化等严重的病理变化,且呈剂量和时间依赖性。还发现该合成大麻素引发了器官中的细胞凋亡。结果表明,受大麻素影响最严重的器官是肾脏。

结论

本研究首次表明CUMYL-4CN-BINACA对健康雄性白化大鼠有不良影响。可以推测,滥用该大麻素可能会以同样的方式危害人类健康。

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