Related Experiment Video
Updated: Aug 11, 2026
In Vivo Assessment of Alveolar Macrophage Efferocytosis Following Ozone Exposure
Published on: October 22, 2019
Protective effect of urate oxidase on uric acid induced-monocyte apoptosis
Valeria Bordoni1, Massimo De Cal, Mario Rassu
1Department of Nephrology, San Bortolo Hospital, Vicenza, Italy.
Abstract:
Uremic patients have a higher risk of infection and malignancy than normal subjects. Previous studies have deomonstrated that monocytes isolated from uremic patients display an increased apoptosis rate compared to normal subjects; furthermore uremic plasma can increase apoptosis rates on U937, a human monocytic cell line. In several pathological conditions, precipitation of uric acid crystals can lead to renal insufficiency or acute renal failure by different mechanisms. In recent studies uric acid has been shown to induce inflammatory response from monocytes and it has been suggested to be involved in cell dysfunction. Rasburicase is a new recombinant urate oxidase developed to prevent and treat hyperuricaemia in patients with cancer or renal failure; it degrades uric acid to allantoin, a less toxic and more soluble product. In the present study, we aimed at determining whether uric acid may be a factor affecting U937 apoptosis, and whether urate oxidase may reduces or even prevent uric acid induced cell apoptosis. Hoechst staining and internucleosome ledder fragmentation of DNA showed that uric acid increased the percentage of apoptotic cells comparing to the control and that when the U937 cells were incubated with uric acid and urate oxidase the percentage of apoptosis significantly decreased (from 43+/-7% to 19+/- 3%, p<0.05). Also, the activity of caspase-8 and caspase-3 showed the same trend (caspase 3: from 2.7+/-0.53 to 1.6+/-0.42; caspase-8: from 2.2+/-0.43 to 1.3+/-0.57). A reduction of intracellular reduced glutathione (GSH) concentration was found in uric acid treated cells while the addition of urate oxidase in the uric acid incubated cells decreased the GSH extrusion. The concentration of TNF-alpha was increased in the sample incubated with uric acid comparing to the control. Uric acid is an inducer of apoptosis on U937 cell line, and therefore it may be a component of the mosaic of uremic toxins both in acute and chronic renal disease. We can hypothesize that uric acid might be directly involved in the apoptotic process trough the activation of both death receptor and mitochondrial-mediated pathways. We have, also, demonstrated that urate oxidase is able to prevent at least in part, the effect of uric acid on U937 apoptosis. This effect might be a result of different mechanisms of action.
Insights
Uric acid induces apoptosis in human monocytic cells, potentially contributing to kidney disease. Urate oxidase effectively reduces this uric acid-induced cell death, offering a potential therapeutic avenue.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Uremic patients exhibit increased susceptibility to infections and malignancies.
- Monocytes from uremic patients show higher apoptosis rates; uremic plasma exacerbates apoptosis in U937 cells.
- Uric acid precipitation is linked to renal dysfunction and may induce monocyte inflammatory responses and cell dysfunction.
Purpose of the Study:
- To investigate if uric acid is a factor in U937 cell apoptosis.
- To determine if urate oxidase can reduce or prevent uric acid-induced apoptosis in U937 cells.
Main Methods:
- U937 cells were treated with uric acid and/or urate oxidase.
- Apoptosis was assessed using Hoechst staining and DNA fragmentation analysis.
- Caspase-8 and caspase-3 activities, intracellular reduced glutathione (GSH) levels, and TNF-alpha concentration were measured.
Main Results:
- Uric acid significantly increased U937 cell apoptosis (43% vs. control).
- Urate oxidase co-incubation reduced apoptosis (19%, p<0.05) and decreased caspase-3 and caspase-8 activity.
- Uric acid lowered GSH concentration and increased TNF-alpha; urate oxidase mitigated these effects.
Conclusions:
- Uric acid acts as an inducer of apoptosis in the U937 cell line, suggesting its role in uremic toxicity.
- Uric acid may trigger apoptosis via death receptor and mitochondrial pathways.
- Urate oxidase demonstrates a partial protective effect against uric acid-induced U937 apoptosis through multiple mechanisms.
