Hyperphosphataemia and NADPH Oxidase Regulation in Pathophysiological Processes: Implications for Oxidative Stress and Disease Progression
Marco Antonio Lacerda‐Abreu, José Roberto Meyer‐Fernandes
Abstract
Hyperphosphataemia is a key contributor to oxidative stress (OS) and cellular dysfunction across various pathological conditions. While numerous studies have associated phosphate overload with redox imbalances, the role of NADPH oxidase (NOX) in this process has received limited attention. NOX enzymes are major enzymatic sources of reactive oxygen species (ROS), and their activation has been implicated in the progression of chronic kidney disease, vascular calcification, metabolic disorders, and cancer development. Under hyperphosphataemic conditions, excessive ROS production exacerbates endothelial dysfunction, promotes vascular smooth muscle cell transdifferentiation, induces chronic inflammation, and facilitates tumour progression. Despite increasing evidence linking phosphate metabolism to NOX activation, the underlying molecular mechanisms remain poorly characterised. This review critically examines the relationship between hyperphosphataemia and NADPH oxidase-mediated OS and explores its impact on disease pathophysiology. By providing an integrated analysis of the current findings, this work aims to highlight the pathological consequences of phosphate-induced OS and identify potential therapeutic strategies to mitigate its effects.