Fiorillo Claudia, Becatti Matteo, Pensalfini Anna, Cecchi Cristina, Lanzilao Luisa, Donzelli Gianpaolo, Nassi Niccolò, Giannini Lara, Borchi Elisabetta, Nassi Paolo
Department of Biochemical Sciences University of Florence, 50134 Florence, Italy.
Free Radic Biol Med. 2008 Sep 15;45(6):839-46. doi: 10.1016/j.freeradbiomed.2008.06.013. Epub 2008 Jun 20.
In this study we explored the effects of curcumin in cardiac cells subjected to a protocol simulating ischemia-reperfusion (IR). Curcumin (10 microM) was administered before ischemia (pretreatment) or at the moment of reperfusion (posttreatment) and its effects were compared to those produced by a reference antioxidant (Trolox) with an equal antioxidant capacity. IR cardiac cells showed clear signs of oxidative stress, impaired mitochondrial activity, and a marked development of both necrotic and apoptotic processes; at the same time, increases in NF-kappaB nuclear translocation and JNK phosphorylation were observed. Curcumin pretreatment was revealed to be the most effective in attenuating all these modifications and, in particular, in reducing the death of IR cells. This confirms that the protective effect of curcumin is not related simply to its antioxidant properties but involves other mechanisms, notably interactions in the NF-kappaB and JNK pathways. These findings suggest that curcumin administration, in particular before the hypoxic challenge, represents a promising approach to protecting cardiac cells against IR injury. In this scenario our results point out the importance of the chronology for the outcome of the treatment and provide a differential valuation of the degree of protection that curcumin can exert by its antioxidant activity or by other mechanisms.
在本研究中,我们探究了姜黄素对经历模拟缺血再灌注(IR)方案的心脏细胞的影响。在缺血前(预处理)或再灌注时(后处理)给予姜黄素(10微摩尔),并将其效果与具有同等抗氧化能力的参考抗氧化剂(曲洛司坦)所产生的效果进行比较。IR心脏细胞表现出氧化应激、线粒体活性受损以及坏死和凋亡过程显著发展的明显迹象;同时,观察到核因子-κB核转位和JNK磷酸化增加。结果显示,姜黄素预处理在减轻所有这些改变方面最为有效,尤其是在减少IR细胞死亡方面。这证实了姜黄素的保护作用并非仅仅与其抗氧化特性相关,而是涉及其他机制,特别是在核因子-κB和JNK途径中的相互作用。这些发现表明,给予姜黄素,特别是在缺氧挑战之前,是保护心脏细胞免受IR损伤的一种有前景的方法。在这种情况下,我们的结果指出了治疗时间顺序对治疗结果的重要性,并对姜黄素通过其抗氧化活性或其他机制所能发挥的保护程度进行了差异评估。