Mladenka Premysl, Zatloukalová Libuse, Simůnek Tomás, Bobrovová Zuzana, Semecký Vladimír, Nachtigal Petr, Hasková Pavlína, Macková Eliska, Vávrová Jaroslava, Holecková Magdaléna, Palicka Vladimir, Hrdina Radomír
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology, Czech Republic.
Toxicology. 2009 Jan 8;255(1-2):25-32. doi: 10.1016/j.tox.2008.09.027. Epub 2008 Oct 17.
High levels of catecholamines are cardiotoxic and may trigger acute myocardial infarction (AMI). Similarly, the synthetic catecholamine isoprenaline (ISO) evokes a pathological state similar to AMI. During AMI there is a marked increase of free iron and copper which are crucial catalysts of reactive oxygen species formation. Rutin, a natural flavonoid glycoside possessing free radical scavenging and iron/copper chelating activity, may therefore be potentially useful in reduction of catecholamine cardiotoxicity as was previously demonstrated after its long-term peroral administration. Male Wistar:Han rats received rutin (46 or 11.5 mg kg(-1) i.v.) alone or with necrogenic dose of ISO (100 mg kg(-1) s.c.). Haemodynamic parameters were measured 24h after drug application together with analysis of blood, myocardial content of elements and histological examination. Results were confirmed by cytotoxicity studies using cardiomyoblast cell line H9c2. Rutin in a dose of 46 mg kg(-1) aggravated ISO-cardiotoxicity while the dose of 11 mg kg(-1) had no effect. These unexpected results were in agreement with in vitro experiments, where co-incubation with larger concentrations of rutin significantly augmented ISO cytotoxicity. Our results, in contrast to previous studies in the literature, suggest that the reported positive effects of peroral administration of rutin were unlikely to have been mediated by rutin per se but probably by its metabolite(s) or by some other, at this moment, unknown adaptive mechanism(s), which merit further investigation.
高水平的儿茶酚胺具有心脏毒性，可能引发急性心肌梗死（AMI）。同样，合成儿茶酚胺异丙肾上腺素（ISO）也会诱发与AMI相似的病理状态。在AMI期间，游离铁和铜显著增加，它们是活性氧形成的关键催化剂。芦丁是一种具有自由基清除和铁/铜螯合活性的天然黄酮糖苷，因此可能在降低儿茶酚胺心脏毒性方面具有潜在作用，此前其长期口服给药后已得到证实。雄性Wistar:Han大鼠单独接受芦丁（46或11.5 mg kg⁻¹静脉注射）或与致坏死剂量的ISO（100 mg kg⁻¹皮下注射）联合给药。给药24小时后测量血流动力学参数，并分析血液、心肌元素含量及进行组织学检查。使用心肌母细胞系H9c2进行细胞毒性研究证实了结果。46 mg kg⁻¹剂量的芦丁加重了ISO的心脏毒性，而11 mg kg⁻¹剂量则无影响。这些意外结果与体外实验一致，在体外实验中，与较高浓度的芦丁共同孵育显著增强了ISO的细胞毒性。与文献中先前的研究相反，我们的结果表明，口服芦丁所报道的积极作用不太可能是由芦丁本身介导的，而可能是由其代谢产物或目前未知的其他适应性机制介导的，这值得进一步研究。
