THE ANTI‐INFLAMMATORY EFFECTS OF ADELMIDROL + SODIUM HYALURONATE (VESSILEN®) IN PRECLINICAL AND CLINICAL STUDIES

Abstract

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder condition characterized by frequent urination, bladder inflammation and pain. It is a particular challenging disease and a clear unmet medical need in terms of identifying new therapeutic strategies. Adelmidrol, the diethanolamide derivative of azelaic acid, represents an effective treatment for human inflammatory disorders. The aim of study was first, to evaluate the anti‐inflammatory effects of intravesical Vessilen® administration (a new formulation of 2% adelmidrol + 0.1% sodium hyaluronate) in acute and chronic animal models of cystitis induced by a single or repetitive intraperitoneal injection of cyclophosphamide (CYP) and then, in patients with IC/PBS treated once weekly by endo‐bladder instillation of Vessilen® for 8 weeks.CYP instillation caused macroscopic and histological bladder alterations, inflammatory infiltrate, increased mast cell number and bladder pain that were reduced by Vessilen® treatment. In addition, an increased expression of nitrotyrosine, a marker of oxidative stress and a decreased expression of endothelial tight junction zonula occludens‐1 were found in CYP‐injected animals. Vessilen® diminished nitrotyrosine and increased zonula occludens‐1 formation. To characterize the inflammatory state and possible reactive oxygen species‐induced pathways involved during chronic cystitis, we also analyzed the nuclear factor‐κB pathway and expression of inducible nitric oxide synthase, interleukin‐1β and monocyte chemoattractant protein‐1. Vessilen® inhibited nuclear factor‐κB pathway and inflammatory mediator levels. Moreover, an increase in nerve growth factor was also found in chronic CYP‐induced cystitis triggering inflammatory response and mechanical hyperalgesia. In that regard, Vessilen® treatment reduced mechanical allodynia and nerve growth factor levels. Interestingly, a reduction in symptom intensity and a significant improvement in the assessment of quality of life were also evident in IC/PBS patients treated with Vessilen®.Thus, in conclusion, we demonstrate that Vessilen® treatment could be a new therapeutic approach in the treatment of human cystitis.Support or Funding Informationno fundingThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.