精氨酸酶-2抑制剂酚类化合物致敏和致突变作用的研究

L. Korokina, M. Pokrovskii, I. S. Kochkarova, O. N. Pokopeiko, S. Povetkin
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引用次数: 0

摘要

致敏和过敏性疾病的一大危险因素是对动物过敏原的易感性。除螨虫和蟑螂外,最重要的动物过敏原来自哺乳动物。对KUD975的致敏性进行实验,实验对象为体重300±20 g的两性性成熟白化豚鼠。在致敏性和致突变性的初步评估中,通过建立活跃的皮肤过敏反应来研究KUD975的致敏性。研究了显性致死突变诱导试验的致突变性。在研究中,体重180-220 g的杂交雄性大鼠以106 mg/kg的剂量灌胃KUD975,相当于估计治疗剂量的40倍。根据精子发生的阶段,每周以每雄3头的比例种植完整雌。实验代码为KUD975的酚类化合物甲酯(2 -((1-羟基萘-2-基)硫(乙酰))- d -脯氨酸)的显性致死突变诱导试验对豚鼠活性皮肤过敏反应配方中的致敏效应和致突变性的研究表明,化合物KUD975没有致敏和致突变性的迹象。鉴于本研究结果,以及已有的毒理学安全性、药理活性研究,可以推荐甲酯(2 -((1-羟基萘-2-基)硫代)乙酰基)- d -脯氨酸kud975作为作用于精氨酸酶-2的药物进一步研究,用于治疗和预防多种内皮相关疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Investigation of Allergenic and Mutagenic Effects of Phenolic Compound, an Arignase-2 Inhibitor
A big risk factor for sensitization and allergic diseases is susceptibility to animal allergens. The most significant animal allergens are derived from mammals, besides mites and cockroaches. The experiments on the allergenic properties of KUD975 were carried out on bisexual sexually mature albino guinea pigs weighing 300 ± 20 g. During the initial assessment of allergenic and mutagenic properties, the allergenic properties of KUD975 were studied by setting up an active skin anaphylaxis reaction. Mutagenicity in the test of induction of dominant lethal mutations was studied. For research, outbred male rats weighing 180-220 g KUD975 was administered intragastrically at a dose of 106 mg/kg, which corresponds to a 40-fold estimated therapeutic dose. Planting intact females at the rate of 3 heads for each male was performed weekly according to the stages of spermatogenesis. The study of the allergenic effect in the formulation of the reaction of active skin anaphylaxis in guinea pigs and mutagenicity in the test for the induction of dominant lethal mutations of the phenolic compound methyl ester (2 - ((1-hydroxy naphthalene-2-yl) thio) acetyl) -D-proline under the laboratory code KUD975 showed no signs of allergenicity and mutagenicity of compound KUD975. Given the results of this study, as well as the previously conducted study of toxicological safety, pharmacological activity, methyl ester (2 - ((1-hydroxy naphthalene-2-yl) thio) acetyl) -D-proline KUD-975 can be recommended for further study as a medicinal agent acting on arignase-2 for the treatment and prevention of a number of endothelium-associated diseases.
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