Franck T, Kohnen S, Grulke S, Neven P, Goutman Y, Peters F, Pirotte B, Deby-Dupont G, Serteyn D
Department of Clinical Sciences, Equine Clinic, Veterinary Institute B 41, University of Liège - Sart Tilman, Liège, Belgium.
Physiol Res. 2008;57(4):577-587. doi: 10.33549/physiolres.931086. Epub 2007 Jul 26.
In the horse, the inflammation response to various pathologies (intestinal strangulations, laminitis, etc.) involves an excessive stimulation of the polymorphonuclear neutrophils releasing reactive oxygen species (ROS) and myeloperoxidase (MPO). The aim of the present work was to study the effect of natural polyphenols, curcuminoids and tetrahydrocurcuminoids (THC) on isolated stimulated equine neutrophils and on the activity of purified MPO. The ROS production and the release of MPO by activated neutrophils were measured by chemiluminescence and ELISA techniques, respectively. The activity of purified MPO was measured by studying its nitration, chlorination or oxidation capacity and by using an original method called SIEFED allowing the study of drug interaction with the enzyme without interferences of the medium. Curcuminoids and THC had dose-dependent inhibitory effects on ROS production and MPO release by activated neutrophils and on purified MPO activity. We suggest that the higher efficacy of curcuminoids versus THC could be explained, at least partially, by its chemical structure: the conjugated double bounds and the plane structure of curcuminoids made easier the neutralization of the radical species generated by activated neutrophils and the interaction of the drug with the active site of MPO. These inhibitory effects of curcuminoids on the oxidant activity of equine neutrophils and on MPO activity open therapeutic perspectives in equine pathologies with excessive inflammatory reactions.
在马体内，对各种病理状况（如肠绞窄、蹄叶炎等）的炎症反应涉及多形核中性粒细胞的过度刺激，从而释放活性氧（ROS）和髓过氧化物酶（MPO）。本研究的目的是研究天然多酚、姜黄素类化合物和四氢姜黄素类化合物（THC）对分离的受刺激马中性粒细胞以及纯化MPO活性的影响。分别通过化学发光和酶联免疫吸附测定（ELISA）技术测量活化中性粒细胞产生的ROS和MPO的释放量。通过研究其硝化、氯化或氧化能力，并使用一种名为SIEFED的原始方法来测量纯化MPO的活性，该方法可在不受培养基干扰的情况下研究药物与酶的相互作用。姜黄素类化合物和THC对活化中性粒细胞产生的ROS和MPO释放以及纯化MPO活性具有剂量依赖性抑制作用。我们认为，姜黄素类化合物相对于THC具有更高疗效，至少部分原因可能是其化学结构：姜黄素类化合物的共轭双键和平坦结构使其更容易中和活化中性粒细胞产生的自由基，并使药物与MPO的活性位点相互作用。姜黄素类化合物对马中性粒细胞氧化活性和MPO活性的这些抑制作用为具有过度炎症反应的马病理状况开辟了治疗前景。
