Beukelman C J, van den Berg A J J, Hoekstra M J, Uhl R, Reimer K, Mueller S
Medicinal Chemistry & Chemical Biology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, University, The Netherlands.
Burns. 2008 Sep;34(6):845-55. doi: 10.1016/j.burns.2007.11.014. Epub 2008 Apr 18.
A liposomal hydrogel with 3% povidone-iodine (PVP-ILH, Repithel) has shown clinical benefit in settings where inflammation and/or reactive oxygen species are thought to impede wound healing (e.g., burns, chronic wounds and in smokers). This in vitro study investigated whether PVP-ILH is able to reduce inflammatory events responsible for the impairment of the wound healing process in such patients. Therefore, the following assays were conducted with PVP-ILH (and derived control hydrogels to identify the component responsible for the effect): inhibition of reactive oxygen species production by human polymorphonuclear neutrophils (PMNs) and in a cell-free system, oxygen consumption assay of PMNs (prior to oxidative burst), inhibition of human complement (limiting the generation of complement factors), mast cell degranulation, nitric oxide production by murine macrophages and TNF-alpha production by human monocytes/macrophages. Where toxicity could cause cell inhibition, cell viability was assessed. PVP-ILH and its components interacted in our series of bioassays at various stages in the inflammation cascade. Scavenging of superoxide anions was the most pronounced effect. Furthermore, povidone-iodine inhibited PMN production of reactive oxygen species (inhibition of oxygen consumption) and a mast cell inhibitory (stabilising) activity was observed. Based on these results, the clinically observed, beneficial wound healing effects of PVP-ILH may also be attributed to an impediment of inflammatory activity, mainly by iodine's free radical scavenging. Controlling oxidative stress in the wound may be of great importance, especially since further reactions as, e.g., the formation of peroxynitrite from NO and ROS are prevented.
一种含有3%聚维酮碘的脂质体水凝胶(PVP - ILH,Repithel)已在炎症和/或活性氧被认为会阻碍伤口愈合的情况下(如烧伤、慢性伤口以及吸烟者)显示出临床益处。这项体外研究调查了PVP - ILH是否能够减少此类患者伤口愈合过程受损所涉及的炎症事件。因此,对PVP - ILH(以及衍生的对照水凝胶以确定起作用的成分)进行了以下检测:人多形核中性粒细胞(PMN)产生活性氧的抑制作用以及在无细胞系统中PMN的氧消耗检测(在氧化爆发之前)、人补体的抑制作用(限制补体因子的产生)、肥大细胞脱颗粒、小鼠巨噬细胞产生一氧化氮以及人单核细胞/巨噬细胞产生肿瘤坏死因子 - α。在毒性可能导致细胞抑制的情况下,评估细胞活力。PVP - ILH及其成分在我们一系列的生物检测中,在炎症级联反应的各个阶段相互作用。超氧阴离子的清除是最显著的效果。此外,聚维酮碘抑制PMN产生活性氧(抑制氧消耗),并观察到肥大细胞抑制(稳定)活性。基于这些结果,临床上观察到的PVP - ILH对伤口愈合的有益作用也可能归因于炎症活性的阻碍,主要是通过碘的自由基清除作用。控制伤口中的氧化应激可能非常重要,特别是因为可以防止进一步的反应,例如由一氧化氮和活性氧形成过氧亚硝酸盐。