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蒽呋喃对家兔的亚慢性经口毒性研究

Subchronic Toxicity Study of Oral Anthrafuran on Rabbits.

作者信息

Treshchalin Michael I, Treshalina Helen M, Golibrodo Vasilisa A, Shchekotikhin Andrey E, Pereverzeva Eleonora R

机构信息

Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia.

Mendeleyev University of Chemical Technology, 9 Miusskaya Square, 125047 Moscow, Russia.

出版信息

Pharmaceuticals (Basel). 2021 Sep 4;14(9):900. doi: 10.3390/ph14090900.

Abstract

A new antitumor multi-target drug anthrafuran, with cellular targets such as topoisomerase I/II and some protein kinases, was obtained in Gause Institute of New Antibiotics and was demonstrated to have a reliable specific effect on different murine and human tumor models by oral administration. In this study, we focused on the evaluation of subchronic toxicity of oral anthrafuran drug formulation (AF) on Chinchilla rabbits. The absence of any changes in the condition or behavior of animals was shown for oral anthrafuran. Changes with reversible and dose-dependent hepato- and nephrotoxicity at low doses, as well as hemato- and gastrointestinal toxicity at high doses, were confirmed pathomorphologically. The identified toxic properties are extremely valuable, since oral anthrafuran does not have the limiting cardio- and myelotoxicity. Anthrafuran with 2 mg/kg/day or 6 mg/kg/day doses was administrated orally over 15 days. Investigations include assessment of the body weight, hematological and serum biochemical parameters and urinalysis, electrocardiography and pathomorphological evaluation of the internal organs. Quantitative data were processed statistically with Student's -Test, < 0.05. Revealed during the subchronic study were the favorable toxicological properties of oral anthrafuran as opposed to clinical anthracyclines, oral idarubicin, or parenteral doxorubicin, which allows it to be considered promising for further research.

摘要

一种新的抗肿瘤多靶点药物蒽呋喃,其细胞靶点包括拓扑异构酶I/II和一些蛋白激酶,是在高斯新抗生素研究所获得的,并通过口服给药证明对不同的小鼠和人类肿瘤模型具有可靠的特效。在本研究中,我们重点评估了口服蒽呋喃药物制剂(AF)对龙猫兔的亚慢性毒性。口服蒽呋喃后,动物的状况或行为未出现任何变化。低剂量时出现可逆的剂量依赖性肝毒性和肾毒性变化,高剂量时出现血液毒性和胃肠道毒性变化,这些变化通过病理形态学得到证实。所确定的毒性特性极具价值,因为口服蒽呋喃没有限制性的心脏毒性和骨髓毒性。以2毫克/千克/天或6毫克/千克/天的剂量口服蒽呋喃,持续15天。研究包括评估体重、血液学和血清生化参数、尿液分析、心电图以及内脏器官的病理形态学评估。定量数据采用学生t检验进行统计学处理,P<0.05。亚慢性研究期间发现,口服蒽呋喃与临床使用的蒽环类药物、口服伊达比星或静脉注射多柔比星相比,具有良好的毒理学特性,这使其有望进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7fca/8464656/53f91e7c2fe0/pharmaceuticals-14-00900-g001.jpg

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