Potential role of oxidative stress in the pathogenesis of diabetic bladder dysfunction

Diabetes mellitus is a chronic metabolic disease, posing a considerable threat to global public health. Treating systemic comorbidities has been one of the greatest clinical challenges in the management of diabetes. Diabetic bladder dysfunction, characterized by detrusor overactivity during the early stage of the disease and detrusor underactivity during the late stage, is a common urological complication of diabetes. Oxidative stress is thought to trigger hyperglycaemia-dependent tissue damage in multiple organs; thus, a growing body of literature has suggested a possible link between functional changes in urothelium, muscle and the corresponding innervations. Improved understanding of the mechanisms of oxidative stress could lead to the development of novel therapeutics to restore the redox equilibrium and scavenge excessive free radicals to normalize bladder function in patients with diabetes. Diabetic bladder dysfunction (DBD) is a common complication of diabetes. Hyperglycaemia-induced oxidative stress is thought to mediate functional changes in organs and tissues affected by DBD. In this Review, the authors provide an overview of mechanisms and consequences of oxidative stress, focusing on the role of diabetes-induced oxidative stress in generating dysfunctions at the level of the urothelium, smooth muscle contractility and nerve structures involved in DBD pathogenesis. Key points Oxidative stress, characterized by either excessive reactive oxygen species production or disturbed antioxidant regulation, occurs in biological systems in normal and pathological conditions. In physiological conditions, reactive oxygen species have a crucial role in cell metabolism, proliferation, differentiation, inflammatory response and preservation of mitochondrial function. The balance between oxidants and antioxidants is maintained through several intertwined mechanisms that could be vulnerable to hyperglycaemia, leading to dysregulated oxidative stress and diabetic complications. Diabetic bladder dysfunction (DBD) can manifest with functional abnormalities varying over time, characterized by a sensory urgency in the early stage, and an impaired sensation of bladder fullness and impaired bladder emptying in the late stage. Hyperglycaemia-induced oxidative stress leading to DBD might also be responsible for impaired contractility of smooth muscle, altered sensory response of urothelium, and slowed conduction of lower urinary tract innervation. In-depth research on dys