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从 Platonia insignis Mart 种子中分离得到的多聚异戊二烯基二苯甲酮 Garcinielliptone FC 的前临床毒理学:互变异构对。

Pre-clinical toxicology of garcinielliptone FC, a tautomeric pair of polyprenylated benzophenone, isolated from Platonia insignis Mart seeds.

机构信息

Department of Phamacy, Laboratory of Research in Experimental Neurochemistry (LAPNEX), Federal University of Piauí, Teresina, CEP 64049-550, Piauí, Brazil.

Department of Phamacy, Laboratory of Research in Experimental Neurochemistry (LAPNEX), Federal University of Piauí, Teresina, CEP 64049-550, Piauí, Brazil.

出版信息

Phytomedicine. 2016 May 15;23(5):477-82. doi: 10.1016/j.phymed.2016.02.013. Epub 2016 Mar 8.

Abstract

BACKGROUND

Garcinielliptone FC (GFC) is a tautomeric pair of polyprenylated benzophenone, which has proven to have antiepileptic, cytotoxic and antioxidant activity.

PURPOSE

The aim of this study was to investigate the biochemical, hematological and pathological effects of the acute toxicity study as well as to assess the locomotor activity and motor coordination in mice treated with GFC.

METHODS

Swiss mice of both sexes weighing 25-30 g divided into three separate groups of five animals matched by weight and size. GFC was aseptically suspended in 0.05% Tween 80, dissolved in 0.9% saline (vehicle) and administered orally (p.o.) and intraperitoneally (i.p.) (500, 1000 and 2000 mg/kg). The acute toxicity study was performed in compliance with the Anvisa regulations.

RESULTS

Behavioral manifestations of toxicity, such as state of consciousness, coordination, muscle tone, reflexes, the activity on the central nervous system (shake, seizures, Straub tail reaction and anesthesia) and the activity of the autonomic nervous system (lacrimation, ptosis, urination, piloerection, hypothermia, breathing and hyperemia) were not seen in any of the animals treated with doses of 500, 1000 and 2000 mg/kg. Additionally, no significant difference in body weight, food and water intake, excreta production or macroscopic changes in the organs of treated animals were detected in comparison with control group. GFC did not affect the locomotor activity and motor coordination of the animals.

CONCLUSION

The acute toxicity study indicated that GFC treatment, at selected doses given orally and intraperitoneally, showed relatively low risk of toxicity in all test animals, suggesting that it is safe for further investigation.

摘要

背景

藤黄菌素 FC(GFC)是一种多聚异戊二烯基二苯甲酮的互变异构体,已被证明具有抗癫痫、细胞毒性和抗氧化活性。

目的

本研究旨在研究急性毒性研究中的生化、血液学和病理学影响,并评估 GFC 处理的小鼠的运动活动和运动协调能力。

方法

将 25-30 克重的雄性和雌性瑞士小鼠分为三组,每组五只动物,按体重和大小匹配。GFC 无菌悬浮于 0.05%吐温 80 中,溶解于 0.9%生理盐水(载体)中,并口服(p.o.)和腹腔内(i.p.)给药(500、1000 和 2000 mg/kg)。急性毒性研究符合 Anvisa 法规进行。

结果

在任何接受 500、1000 和 2000 mg/kg 剂量治疗的动物中,均未观察到毒性的行为表现,如意识状态、协调、肌肉张力、反射、中枢神经系统活动(摇晃、癫痫、Straub 尾巴反应和麻醉)和自主神经系统活动(流泪、眼睑下垂、排尿、毛发竖起、体温过低、呼吸和充血)。此外,与对照组相比,未观察到处理动物的体重、食物和水摄入量、排泄物产生或器官的宏观变化有任何显著差异。GFC 未影响动物的运动活动和运动协调能力。

结论

急性毒性研究表明,口服和腹腔内给予选定剂量的 GFC 治疗在所有试验动物中显示出相对较低的毒性风险,表明其进一步研究是安全的。

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