Title : Repurposing tavaborole for enhanced wound healing in chronic venous leg ulcers: A study on arginase inhibition and inflammatory modulation
Abstract:
Chronic venous insufficiency (CVI) often leads to venous leg ulcers (VLUs), which present significant challenges in wound healing due to venous reflux, elevated pressure, inflammation, and endothelial dysfunction. This study investigates the potential of tavaborole, an arginase inhibitor, in improving wound healing in VLUs by targeting key factors such as arginase activity, nitric oxide production, oxidative stress, and the inflammatory response. RAW 264.7 macrophages were treated with various concentrations of tavaborole and compared to L-Norvaline, a standard arginase inhibitor. The effects on cell viability, arginase activity, nitric oxide (NO) production, reactive oxygen species (ROS) generation, and wound healing were assessed through MTT, arginase inhibition assays, Griess reagent, ROS fluorescence assay, and scratch assays. Additionally, gene expression analysis of arginase-1 was conducted via quantitative real-time PCR (qRT-PCR) to examine the impact of tavaborole on arginase-1 expression. The results revealed that tavaborole significantly inhibited arginase activity, reduced NO production, and lowered IL-6 levels, compared to L-Norvaline. Gene expression analysis of arginase-1 confirmed a reduction in arginase-1 expression in tavaborole-treated cells, indicating its role in modulating arginase activity. Furthermore, tavaborole demonstrated promising effects in reducing ROS production and promoting wound healing, as observed in the scratch assays. In conclusion, tavaborole appears to be a promising therapeutic agent for enhancing wound healing in VLUs by modulating inflammatory pathways, reducing oxidative stress, and restoring endothelial function. Its potential in targeting key factors such as arginase activity and nitric oxide production makes it a valuable candidate for further investigation in chronic wound management.
Keywords: Tavaborole, Arginase Inhibition, RAW 264.7 Macrophages, Venous Leg Ulcers, Wound Healing
