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新型抗肿瘤4-噻唑烷酮衍生物与阿霉素在含聚乙二醇聚合物载体复合物中对大鼠血清心脏毒性作用的大鼠血清生化指标研究

[Study of rat blood serum biochemical indicators of cardiotoxic action of novel antitumor 4-thiazolidinone derivatives and doxorubicin in complexes with polyethylene glycol-containing polymeric carrier in the rat blood serum].

作者信息

Kobylyns'ka L I, Havryliuk D Ia, Riabtseva A O, Mitina N Ie, Zaichenko O S, Zimenkovskyĭ B S, Stoĭka R S

出版信息

Ukr Biochem J. 2014 Nov-Dec;86(6):84-95.

Abstract

The aim of this study was to measure the activity of enzymes which reflect cardiotoxic action in rats of novel synthetic 4-thiazolidone derivatives--3882, 3288 and 3833 that demonstrated antineoplastic effect in vitro towards 60 lines of human tumor cells tested in the framework of the program of screening new anticancer drugs at the National Cancer Institute (USA). Such action of these compounds was compared with the effect of well known anticancer agent doxorubicin and after conjugation of all above mentioned substances with new polyethylenglycol-containing polymeric comb-like carrier that was synthesized by the authors. Among the biochemical indicators of cardiotoxic action of anticancer agents, activity of the following enzymes in rat blood serum showed to be the most informative: creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransterase. Tenfold injection of doxorubicin in a dose of 5.5 mg/kg of weight caused rats' death, while 3882, 3288 and 3833 preparations had not such action. Application of the doxorubicin in combination with polymeric carrier prolonged the survival time to 20 days. Thus, the injection of anticancer agents in a complex with polymeric carrier provides a significant decrease in their cardiotoxicity that was confirmed by the corresponding changes in the activity of marker enzymes: creatine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in blood serum of treated rats.

摘要

本研究的目的是测定新型合成4-噻唑烷二酮衍生物——3882、3288和3833在大鼠体内反映心脏毒性作用的酶活性。这些衍生物在美国国立癌症研究所(National Cancer Institute)的新型抗癌药物筛选项目框架下,对60种人类肿瘤细胞系具有体外抗肿瘤作用。将这些化合物的这种作用与著名抗癌药物阿霉素的作用进行比较,并将上述所有物质与作者合成的新型含聚乙二醇的聚合物梳状载体进行偶联。在抗癌药物心脏毒性作用的生化指标中,大鼠血清中以下几种酶的活性显示出最具信息量:肌酸激酶、乳酸脱氢酶、天冬氨酸转氨酶和丙氨酸转氨酶。以5.5mg/kg体重的剂量给大鼠注射10倍剂量的阿霉素会导致大鼠死亡,而3882、3288和3833制剂则没有这种作用。将阿霉素与聚合物载体联合应用可使存活时间延长至20天。因此,将抗癌药物与聚合物载体联合注射可显著降低其心脏毒性,这一点通过处理大鼠血清中标记酶(肌酸激酶、乳酸脱氢酶、天冬氨酸转氨酶和丙氨酸转氨酶)活性的相应变化得到证实。

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