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一种光稳定剂Tinuvin 770诱导的成年大鼠心肌细胞毒性损伤。

A light stabilizer Tinuvin 770-induced toxic injury of adult rat cardiac myocytes.

作者信息

Sótonyi P, Keller E, Járay J, Nemes B, Benkõ T, Kovács A, Tolokán A, Rajs I

机构信息

Department of Transplantation and Surgery, Semmelweis University of Medicine, Baross u. 23-25, 1082, Budapest, Hungary.

出版信息

Forensic Sci Int. 2001 Jul 15;119(3):322-7. doi: 10.1016/s0379-0738(00)00462-x.

Abstract

Tinuvin 770/bis(2,2,6,6-tetramethyl-4-piperidinyl)sebacate is a worldwide used light stabilizer for plastic materials like polyolefins. Tinuvin 770 is a biologically active component of polypropylene tubes. Glossmann and his study group managed to extract this compound by aqueous or organic solvents from laboratory plastic tubes, and propose that Tinuvin 770 is a potent blocker of L-type Ca(2+)-channel through the phenylalkylamine and benzothiazepine-selective drug binding domains of the alpha(1) subunit of the receptor [Proc. Natl. Acad. Sci. U.S.A. 90 (1993) 9523]. We examined the direct morphological effect of Tinuvin 770 in give 25nmol, 0, 30, 60, 120 minute exposure time in isolated cardiomyocytes from adult rats. Incubation of myocytes with Tinuvin resulted in a progressive decline of rod-shaped and viable cells. It was accompanied by an increase in number of hypercontracted myocytes with microbleb formation compared to control and depletion of ATP level. In summary, our results demonstrate that plasma membrane damage and hypercontraction are manifestations of Tinuvin-induced injury of isolated cardiomyocytes.

摘要

Tinuvin 770/癸二酸双(2,2,6,6-四甲基-4-哌啶基)酯是一种在全球范围内用于聚烯烃等塑料材料的光稳定剂。Tinuvin 770是聚丙烯管的一种生物活性成分。Glossmann和他的研究小组成功地通过水性或有机溶剂从实验室塑料管中提取了这种化合物,并提出Tinuvin 770是通过受体α(1)亚基的苯烷基胺和苯并硫氮杂䓬选择性药物结合域对L型钙通道的有效阻滞剂[美国国家科学院院刊90 (1993) 9523]。我们在成年大鼠分离的心肌细胞中,以25nmol的剂量,分别在0、30、60、120分钟的暴露时间下,研究了Tinuvin 770的直接形态学效应。用Tinuvin孵育心肌细胞导致杆状活细胞逐渐减少。与对照组相比,伴有微泡形成的过度收缩心肌细胞数量增加以及ATP水平降低。总之,我们的结果表明,质膜损伤和过度收缩是Tinuvin诱导的分离心肌细胞损伤的表现。

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