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单萜烯α-松油醇对正常和肿瘤真核细胞的遗传毒性特征。

Toxicogenetic profile of the monoterpene alpha-terpineol on normal and tumor eukaryotic cells.

机构信息

Postgraduation Program in Pharmaceutical Sciences, Laboratory of Research in Toxicological Genetics (LAPGENIC), Federal University of Piauí, Teresina, Brazil.

Department of Biochemistry and Pharmacology, Federal University of Piauí, Teresina, Brazil.

出版信息

Drug Chem Toxicol. 2024 Jul;47(4):427-435. doi: 10.1080/01480545.2023.2188440. Epub 2023 Mar 13.

Abstract

Alpha-terpineol is a monoterpene alcohol found in essential oils from medicinal plants with some well-known pharmacological activities and widely used in cosmetics. However, the toxicological effects and additional pharmacological activities need to be clarified. Thus, the study evaluated the toxic, cytotoxic, genotoxic, hemolytic, and oxidative potential of alpha-terpineol in non-clinical bioassays. Different concentrations of alpha-terpineol were used in bioassays, including MTT (50, 100, 200, and 400 μg/mL), (6.25-400 μg/mL), (10, 50, and 100 μg/mL), comet assay (100, 200, and 500 μg/mL), cytokinesis-block micronucleus (100, 250, and 500 μg/mL), confocal microscopy for apoptosis quantification (100 and 500 μg/mL), hemolysis and central disk test (10, 35, and 75 μg/mL). For the MTT test, alpha-terpineol was more cytotoxic on melanoma murine B16-F10 cells rather than macrophages. For test, alpha-terpineol showed LC of 68.29 and 76.36 μg/mL for 24 h and 48 h of exposure time, respectively. Meanwhile, alpha-terpineol was also cytotoxic to meristematic cells, which revealed inhibition of cellular division and mutagenic action by formation of bridges and delayed anaphases. The compound increased damage index and frequency of damage corroborated by the presence of micronuclei, bridges and nuclear buds at 500 μg/mL, but it caused neither hemolysis, oxidative damage on the nor cell death in normal fibroblasts. The findings indicate alpha-terpineol has cytotoxic potential by cytogenetic and molecular mechanisms associated with apoptosis and probable target effects against melanoma cells.

摘要

α-松油醇是一种单萜醇,存在于药用植物的精油中,具有一些众所周知的药理学活性,广泛应用于化妆品中。然而,其毒理学效应和其他药理学活性需要进一步阐明。因此,本研究在非临床生物测定中评估了α-松油醇的毒性、细胞毒性、遗传毒性、溶血和氧化潜力。在生物测定中使用了不同浓度的α-松油醇,包括 MTT(50、100、200 和 400μg/mL)、(6.25-400μg/mL)、彗星试验(100、200 和 500μg/mL)、细胞分裂阻断微核试验(100、250 和 500μg/mL)、细胞凋亡定量共聚焦显微镜检测(100 和 500μg/mL)、溶血和中央盘试验(10、35 和 75μg/mL)。在 MTT 试验中,α-松油醇对黑色素瘤鼠 B16-F10 细胞的细胞毒性大于对巨噬细胞的细胞毒性。在 试验中,α-松油醇暴露 24 和 48 小时的 LC 分别为 68.29 和 76.36μg/mL。同时,α-松油醇对有丝分裂细胞也具有细胞毒性,表现为细胞分裂抑制和形成桥和延迟后期导致的诱变作用。该化合物在 500μg/mL 时增加了损伤指数和损伤频率,微核、桥和核芽的存在证实了这一点,但它既没有引起溶血,也没有对 造成氧化损伤,也没有导致正常成纤维细胞死亡。这些发现表明,α-松油醇通过与细胞凋亡相关的细胞遗传学和分子机制以及对黑色素瘤细胞的可能靶向作用具有细胞毒性潜力。

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