Carbonyl scavengers as pharmacotherapies in degenerative disease: Hydralazine repurposing and challenges in clinical translation

摘要: Abstract During cellular metabolism, spontaneous oxidative damage to unsaturated lipids generates many electrophilic carbonyl compounds that readily attack cell macromolecules, forming adducts are potential drivers of tissue dysfunction. Since such is heightened in degenerative conditions, researchers have assessed the efficacy nucleophilic carbonyl-trapping drugs animal models disorders, anticipating they will protect tissues by intercepting toxic lipid-derived electrophiles (LDEs) within cells. This Commentary explores recent evidence for scavenger two disparate yet significant conditions known involve LDE production, namely spinal cord injury (SCI) and alcoholic liver disease (ALD). Primary emphasis placed on studies utilised hydralazine, a clinically-approved “broad-spectrum” trap multiple LDEs. In addition reviewing hydralazine SCI ALD models, reviews new insights concerning novel lifespan- healthspan-extending properties obtained during model invertebrate organisms, since mechanisms involved seem likely benefit treatment disease. Finally, noting human translation histoprotective been limited, final section address obstacles hamper clinical LDE-trapping therapies while also suggesting strategies overcoming these problems.