Molecular pathways involved in lymphedema: Hydroxytyrosol as a candidate natural compound for treating the effects of lymph accumulation

Abstract

Lymphedema is a chronic accumulation of interstitial fluid due to inefficient lymph drainage. Major causes of lymphedema are malformations of lymphatic vessels, trauma, toxic damage and surgery. The swelling typically affects the limbs. Lymphedema may be primary, caused by genetic mutations and relatively rare, or secondary (acquired), due to external causes such as infections or surgery. Fluid accumulation induces pathological changes: activation of the inflammatory cascade, immune cell infiltration, tissue fibrosis, adipose accumulation. We focused on the inflammatory phenotype mediated by leukotriene B4, a lipid mediator of the inflammatory pathway, and the potential therapeutic effect of hydroxytyrosol. We conducted an electronic search in PubMed using "lymphedema", "lymphedema pathway", "hydroxytyrosol" as keywords. We found that lymphedema deregulates at least six molecular pathways and that hydroxytyrosol, a compound with antioxidant activity, can improve endothelial dysfunction, hemostatic and lipid profiles, and decrease oxidative stress and inflammation through inhibition of leukotriene B4 activity. This review is the first to highlight the possibility of using hydroxytyrosol to treat the secondary effects of lymphedema, especially inflammation. The possible effects of hydroxytyrosol on lymphedema should be tested in vitro and in vivo to find the best way to treat patients with lymphedema in order to improve their health status.

Keywords: Hydroxytyrosol; Leukotriene B4; Lymphedema; Molecular pathways; Oxidative stress.