Uric Acid and Oxidative Stress—Relationship with Cardiovascular, Metabolic, and Renal Impairment

Abstract

Background: The connection between uric acid (UA) and renal impairment is well known due to the urate capacity to precipitate within the tubules or extra-renal system. Emerging studies allege a new hypothesis concerning UA and renal impairment involving a pro-inflammatory status, endothelial dysfunction, and excessive activation of renin–angiotensin–aldosterone system (RAAS). Additionally, hyperuricemia associated with oxidative stress is incriminated in DNA damage, oxidations, inflammatory cytokine production, and even cell apoptosis. There is also increasing evidence regarding the association of hyperuricemia with chronic kidney disease (CKD), cardiovascular disease, and metabolic syndrome or diabetes mellitus. Conclusions: Important aspects need to be clarified regarding hyperuricemia predisposition to oxidative stress and its effects in order to initiate the proper treatment to determine the optimal maintenance of UA level, improving patients’ long-term prognosis and their quality of life.

Dietary fructose and high salt in young male Sprague Dawley rats induces salt‐sensitive changes in renal function in later life

“…Uric acid is a known by‐product of fructose catabolism and has been shown to decrease nitric oxide availability and impair mitochondrial respiration. The reduced mitochondrial respiration ultimately results in preferential glycolysis and the formation of reactive oxygen species (De Becker et al, 2019 ), both of which have been implicated in dysregulated extracellular matrix formation and cell proliferation/apoptosis via the Warburg effect (Gherghina et al, 2022 ; Lunt & Vander Heiden, 2011 ). Whether prior exposure to high fructose during youth alters these or other mechanisms later in life will need further study.…”

Optimization of the extraction process and metabonomics analysis of uric acid-reducing active substances from Gymnadenia R.Br. and its protective effect on hyperuricemia zebrafish

“…The available evidence reveals that the formation of UA is catalyzed by XOD, which is a purported source of ROS, and the changes in XOD and UA are biomarkers of oxidative stress. Additionally, XOD may provide an important source of nitric oxide (NO) that quenches the injurious effects caused by ROS (108)(109)(110). Li et al have shown that febuxostat can reduce the content of serum UA in rats, inhibit the occurrence and development of inflammation, reduce oxidative stress, and reduce damage to cerebral arteries and blood vessels (111).…”

Association of Elevated Serum Uric Acid with Nerve Conduction Function and Peripheral Neuropathy Stratified by Gender and Age in Type 2 Diabetes Patients

“…Intracellular uric acid induces pro-inflammatory biomarkers and activates NADPH oxidases, then further increases ROS production which can lead to pro-oxidative actions [ 42 ]. Oxidative stress induced by hyperuricemia causes various pathophysiology reactions such as inflammatory cytokine release and cell apoptosis [ 43 ]. Uric acid crystals could also activate the inflammasome, leading to the maturation of interleukin-1 and initiation of inflammatory cascades [ 44 ].…”