Department of Biosciences, Institute of Health and Society, Federal University of São Paulo, UNIFESP, Rua Silva Jardim, 136, Room 332, Vila Mathias, Santos, SP, 11050-020, Brazil.
Department of Pathology, Paulista Medical School, Federal University of Sao Paulo, UNIFESP, Sao Paulo, SP, Brazil.
Arch Toxicol. 2024 Jun;98(6):1877-1890. doi: 10.1007/s00204-024-03712-7. Epub 2024 Mar 17.
Cannabis is the most used illicit substance for recreational purposes around the world. However, it has become increasingly common to witness the use of approved cannabis preparations for symptoms management in various diseases. The aim of this study was to investigate the effects of cannabis nano emulsion in the liver of Wistar rats, with different proportions of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). For this, a total of 40 male Wistar rats were distributed into 5 groups, as follows (n = 8 per group): Control: G1, Experimental group (G2): treated with cannabis nano emulsion (THC and CBD) at a dose of 2.5 mg/kg, Experimental group (G3): treated with cannabis nano emulsion (THC and CBD) at a dose of 5 mg/kg, Experimental group (G4): treated with cannabis nano emulsion (CBD) at a dose of 2.5 mg/kg; Experimental group (G5): treated with cannabis nano emulsion (CBD) at a dose of 5 mg/kg. Exposure to the nano emulsion was carried out for 21 days, once a day, orally (gavage). Our results showed that cannabis nano emulsions at higher doses (5 mg/kg), regardless of the composition, induced histopathologic changes in the liver (G3 and G5) in comparison with the control group. In line with that, placental glutathione S-transferase (GST-P) positive foci increased in both G3 and G5 (p < 0.05), as well as the immune expression of Ki-67, vascular endothelial growth factor (VEGF) and p53 (p < 0.05). Also, the nano emulsion intake induced an increase in the number of micronucleated hepatocytes in G5 (p < 0.05) whereas G3 showed an increase in binucleated cells (p < 0.05). As for metanuclear alterations, karyolysis and pyknosis had an increased frequency in G3 (p < 0.05). Taken together, the results show that intake of cannabis nano emulsion may induce degenerative changes and genotoxicity in the liver in higher doses, demonstrating a clear dose-response relationship.
大麻是全球范围内娱乐用途最广泛的非法物质。然而，越来越常见的是，人们开始使用已批准的大麻制剂来治疗各种疾病的症状。本研究的目的是调查不同比例的 delta-9-四氢大麻酚（THC）和大麻二酚（CBD）的大麻纳米乳液对 Wistar 大鼠肝脏的影响。为此，将总共 40 只雄性 Wistar 大鼠分为 5 组，如下所示（每组 8 只）：对照组：G1，实验组（G2）：用 2.5mg/kg 的大麻纳米乳液（THC 和 CBD）治疗，实验组（G3）：用 5mg/kg 的大麻纳米乳液（THC 和 CBD）治疗，实验组（G4）：用 2.5mg/kg 的大麻纳米乳液（CBD）治疗；实验组（G5）：用 5mg/kg 的大麻纳米乳液（CBD）治疗。纳米乳液的暴露时间为 21 天，每天一次，口服（灌胃）。我们的结果表明，与对照组相比，高剂量（5mg/kg）的大麻纳米乳液（无论成分如何）都诱导了肝脏的组织病理学变化（G3 和 G5）。与此一致的是，G3 和 G5 中胎盘谷胱甘肽 S-转移酶（GST-P）阳性焦点增加（p<0.05），Ki-67、血管内皮生长因子（VEGF）和 p53 的免疫表达也增加（p<0.05）。此外，纳米乳液摄入导致 G5 中微核肝细胞数量增加（p<0.05），而 G3 中二倍体细胞增加（p<0.05）。至于多核改变，核溶解和核固缩的频率在 G3 中增加（p<0.05）。综上所述，结果表明，摄入大麻纳米乳液可能会在高剂量下引起肝脏的退行性变化和遗传毒性，表现出明显的剂量反应关系。
