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首页> 外文期刊>Journal of applied toxicology >Preliminary safety evaluation of a taurocholate-conjugated low-molecular-weight heparin derivative (LHT7): a potent angiogenesis inhibitor
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Preliminary safety evaluation of a taurocholate-conjugated low-molecular-weight heparin derivative (LHT7): a potent angiogenesis inhibitor

机译：牛磺酸胆碱结合的低分子量肝素衍生物（LHT7）的初步安全性评估：一种有效的血管生成抑制剂

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In our previous studies, taurocholic acid (TA)-conjugated low-molecular-weight heparin derivative (LHT7) has been proven to be a potent anti-angiogenic agent by demonstrated successful blockage capability of vascular endothelial growth factors (VEGF). Preliminary safety evaluations were conducted based on its mechanism of action and chemical behavior. For this purpose, acute toxicity study, and hematological and serological evaluations were carried out. Additionally, in order to evaluate mechanism-related side effects, both blood pressure and the occurrence of proteinuria were measured using a treatment regime of multiple high doses of LHT7 in a biodistribution study. LD50 values for LHT7 in female and male mice were 56.9 and 64.7 mg kg(-1) doses, respectively. There were no vital fluctuations in the serological and hematological parameters, except for the elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at 100 and 200 mg kg(-1) doses of LHT7, representing vital changes in the liver function. Moreover, the results of mechanism-related studies showed that blood pressure at 50 mg kg(-1) did not change but showed elevated levels of protein in urine. In the biodistribution study, a slight accumulation of LHT7 in the kidney and the liver were observed at the 50 mg kg(-1) repeated dose owing to the presence of bile acid. No fatal damage was observed in this study; most observations were related to the chemical composition or the mechanism of action of the material. Copyright (c) 2014 John Wiley & Sons, Ltd.
机译：在我们以前的研究中，牛磺胆酸（TA）共轭的低分子量肝素衍生物（LHT7）已被证明具有成功的血管内皮生长因子（VEGF）阻断能力，是一种有效的抗血管生成剂。根据其作用机理和化学行为进行了初步安全评估。为此目的，进行了急性毒性研究以及血液学和血清学评估。此外，为了评估与机制相关的副作用，在生物分布研究中使用多个高剂量LHT7的治疗方案对血压和蛋白尿的发生进行了测量。 LHT7在雌性和雄性小鼠中的LD50值分别为56.9和64.7 mg kg（-1）剂量。除了在100和200 mg kg（-1）剂量的LHT7时天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）的水平升高外，血清学和血液学参数没有重要的波动，这代表肝功能的重要变化。此外，与机理相关的研究结果表明，50 mg kg（-1）的血压没有变化，但尿液中的蛋白质水平升高。在生物分布研究中，由于胆汁酸的存在，在50 mg kg（-1）重复剂量下观察到LHT7在肾脏和肝脏中有少量积累。在这项研究中没有观察到致命的损害。大多数观察与材料的化学成分或作用机理有关。版权所有（c）2014 John Wiley＆Sons，Ltd.

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