N-octanoyl dopamine, a non-hemodyanic dopamine derivative, for cell protection during hypothermic organ preservation.
N-octanoyl dopamine, a non-hemodyanic dopamine derivative, for cell protection during hypothermic organ preservation.
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DOI：
10.1371/journal.pone.0009713
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发表时间：
2010-03-16
期刊：
影响因子：
3.7
通讯作者：
Yard BA
中科院分区：
文献类型：
--
作者：
Lösel RM;Schnetzke U;Brinkkoetter PT;Song H;Beck G;Schnuelle P;Höger S;Wehling M;Yard BA
虽然供体多巴胺治疗减少了肾移植受者对移植后透析的需求，但其血流动力学副作用阻碍了多巴胺在供体管理中的应用。因此，新的多巴胺衍生物缺乏任何血液动力学作用，但更有效地保护组织免受冷保存损伤是必要的。我们假设分子结构的变化将产生更有效的化合物，避免任何血液动力学效应。为此，我们评估了保护对冷保存损伤的HUVEC的衰减乳酸脱氢酶（LDH）的释放。通过烷酰基修饰多巴胺可以增加细胞摄取并显着提高保护功效。进一步的变化表明，只有在苯核的邻位或帕拉带有两个羟基的化合物，即强还原剂，才具有保护作用。然而，其他还原剂，如N-乙酰半胱氨酸和抗坏血酸，或NADPH氧化酶抑制剂并不能防止细胞损伤后冷藏。与多巴胺不同，一种原型的新型化合物不会引起血液动力学副作用。总之，我们表明，保护免受冷保存损伤的儿茶酚胺是完全由强大的还原能力和足够的亲脂性。新的多巴胺衍生物可能在供体预处理中具有临床相关性，因为它们完全没有血液动力学作用，它们增加的细胞摄取将减少治疗时间，因此也可能对无心跳供体具有潜在用途。
Although donor dopamine treatment reduces the requirement for post transplantation dialysis in renal transplant recipients, implementation of dopamine in donor management is hampered by its hemodynamic side-effects. Therefore novel dopamine derivatives lacking any hemodynamic actions and yet are more efficacious in protecting tissue from cold preservation injury are warranted. We hypothesized that variation of the molecular structure would yield more efficacious compounds avoid of any hemodynamic effects. To this end, we assessed protection against cold preservation injury in HUVEC by the attenuation of lactate dehydrogenase (LDH) release. Modification of dopamine by an alkanoyl group increased cellular uptake and significantly improved efficacy of protection. Further variation revealed that only compounds bearing two hydroxy groups in ortho or para position at the benzene nucleus, i.e. strong reductants, were protective. However, other reducing agents like N-acetyl cysteine and ascorbate, or NADPH oxidase inhibition did not prevent cellular injury following cold storage. Unlike dopamine, a prototypic novel compound caused no hemodynamic side-effects. In conclusion, we demonstrate that protection against cold preservation injury by catecholamines is exclusively governed by strong reducing capacity and sufficient lipophilicity. The novel dopamine derivatives might be of clinical relevance in donor pre-conditioning as they are completely devoid of hemodynamic action, their increased cellular uptake would reduce time of treatment and therefore also may have a potential use for non-heart beating donors.
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影响因子：
6.2
作者：
Hoeger, Simone;Petrov, Kiril;Yard, Benito A.
通讯作者：
Yard, Benito A.
影响因子：
38.9
作者：
Juste, RN;Moran, L;Soni, N
通讯作者：
Soni, N
影响因子：
6.2
作者：
Salahudeen, AA;Jenkins, JK;Salahudeen, AK
通讯作者：
Salahudeen, AK
影响因子：
19.6
作者：
Schnuelle, P;Lorenz, D;van der Woude, FJ
通讯作者：
van der Woude, FJ
影响因子：
2.8
作者：
Rauen, U;Kerkweg, U;de Groot, H
通讯作者：
de Groot, H