Toxicogenetic profile and antioxidant evaluation of gamma-terpinene: Molecular docking and in vitro and in vivo assays.

IF 2.1 4区 医学 Q3 CHEMISTRY, MULTIDISCIPLINARY
Railson Pereira Souza, Antonielly Campinho Dos Reis, Vinícius Duarte Pimentel, Bianca de Sousa Leal, Milena Monteiro de Freitas, Jefferson da Cruz Esteves, Lara Priscila Freitas Ferreira, Débora Caroline do Nascimento Rodrigues, Rayran Walter Ramos de Sousa, Alyne Pereira Lopes, Maria José Dos Santos Soares, João Marcelo de Castro E Sousa, Paulo Michel Pinheiro Ferreira, Aldeídia Pereira de Oliveira
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引用次数: 0

Abstract

Gamma-terpinene (γ-TPN) is found in several plant species, such as thyme, eucalyptus, rosemary, black cumin, oregano, among others, and is known for antimicrobial, antiparasitic, antinociceptive, anticancer, antiplatelet, and insecticidal activities. Based on this, it was assessed its toxicogenetic and antioxidant profile using in silico, in vitro and in vivo replacement assays. The compound was moderately toxic on Artemia salina nauplii [LC50 value of 136.1 (81.8 - 158.7) µM] and reduced proliferation of melanoma B16-F10 [IC50 value of 38.19 (26.82 - 54.52) μM] tumor cells, without affecting viability of normal RAW 264.7 macrophages and mammalian erythrocytes' membrane. γ-TPN (12.5, 25 and 50 µM) intensively reduced the mitotic index (MI) of dividing Allium cepa meristematic cells in a non-concentration-dependent way and caused increasing in interphase and reduction in prophase cells (p < 0.05). The monoterpene showed in silico affinity to the enzymes catalase and glutathione reductase and in vivo amplification of the catalase activity in erythrocytes of γ-TPN-treated spontaneous hypertensive rats. Increase of binucleated cells was observed at the highest dose (100 mg/kg/day) only. Then, as a natural molecule, γ-TPN isn't free of damaging effects, and further investigations are needed to ensure limiting doses and regulation aspects.

γ -萜烯的毒理学特征和抗氧化评价:分子对接和体外和体内试验。
γ-萜烯(γ-TPN)存在于多种植物中,如百里香、桉树、迷迭香、黑孜然、牛至等,具有抗菌、抗寄生虫、抗感染、抗癌、抗血小板和杀虫活性。在此基础上,采用硅片、体外和体内替代试验对其毒理学和抗氧化特性进行了评估。该化合物对青蒿素(Artemia salina nauplii)有中等毒性[LC50值为136.1 (81.8 ~ 158.7)μM],可抑制黑色素瘤B16-F10 [IC50值为38.19 (26.82 ~ 54.52)μM]肿瘤细胞的增殖,但不影响正常RAW 264.7巨噬细胞和哺乳动物红细胞膜的活性。γ-TPN(12.5、25和50µM)以非浓度依赖的方式显著降低了自发性高血压大鼠的分生组织细胞分裂的有丝分裂指数(MI),导致间期细胞对过氧化氢酶和谷胱甘肽还原酶的亲和力增加,前期细胞对过氧化氢酶和谷胱甘肽还原酶的亲和力降低,红细胞过氧化氢酶活性在体内扩增。仅在最高剂量(100 mg/kg/天)下观察到双核细胞的增加。然后,作为一种天然分子,γ-TPN并非没有破坏性影响,需要进一步的研究来确保限制剂量和调节方面。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Drug and Chemical Toxicology
Drug and Chemical Toxicology 医学-毒理学
CiteScore
6.00
自引率
3.80%
发文量
99
审稿时长
3 months
期刊介绍: Drug and Chemical Toxicology publishes full-length research papers, review articles and short communications that encompass a broad spectrum of toxicological data surrounding risk assessment and harmful exposure. Manuscripts are considered according to their relevance to the journal. Topics include both descriptive and mechanics research that illustrates the risk assessment implications of exposure to toxic agents. Examples of suitable topics include toxicological studies, which are structural examinations on the effects of dose, metabolism, and statistical or mechanism-based approaches to risk assessment. New findings and methods, along with safety evaluations, are also acceptable. Special issues may be reserved to publish symposium summaries, reviews in toxicology, and overviews of the practical interpretation and application of toxicological data.
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