Uricase deficiency causes mild and multiple organ injuries in rats

Fan, Nan; Yu, Yun; Li, Lvyu; Xia, Heng; Dong, Xiangxian; Chen, Huan; Duan, Weigang

doi:10.1371/journal.pone.0256594

Cited by 6 publications

(7 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that uricase deficiency causes multiple mild organ injuries in KDY rats ( Fan et al, 2021 ), which was further verified in the present study. The possible mechanisms underlying these injuries may be associated with Uox, the protein of uricase, or the elevation of SUA, which requires further investigation.…”

Section: Discussionsupporting

confidence: 89%

See 1 more Smart Citation

Dieting alleviates hyperuricemia and organ injuries in uricase-deficient rats via down-regulating cell cycle pathway

Yu,

Wan,

et al. 2023

PeerJ

Self Cite

View full text Add to dashboard Cite

Dieting is a basic treatment for lowering hyperuricemia. Here, we aimed to determine the optimal amount of dietary food that lowers serum uric acid (SUA) without modifying the dietary ingredients in rats. Increased SUA was found in food-deprived 45-day-old uricase-deficient rats (Kunming-DY rats), and the optimal amount of dietary food (75% dietary intake) to lower SUA was established by controlling the amount of food given daily from 25% to 100% for 2 weeks. In addition to lowering SUA by approximately 22.5 ± 20.5%, the optimal amount of dietary food given for 2 weeks inhibited urine uric acid excretion, lowered the uric acid content in multiple organs, improved renal function, lowered serum triglyceride, alleviated organ injuries (e.g., liver, kidney and intestinal tract) at the histological level, and down-regulated the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway of the cell cycle (ko04110). Taken together, these results demonstrate that 75% dietary food effectively lowers the SUA level without modifying dietary ingredients and alleviates the injuries resulting from uricase deficiency or hyperuricemia, the mechanism of which is associated with the down-regulation of the cell cycle pathway.

show abstract

Section: Discussionsupporting

confidence: 89%

“…Uricase deficiency caused multiple mild organ injuries in KDY rats ( Fan et al, 2021 ), similar to the phenomena observed in uricase-deficient mice ( Guo et al, 2019 ). In the control group, swollen hepatic cells were observed, and the sinuses were crowded with swollen hepatic cells, which caused the hepatic sinuses to be very narrow ( Fig.…”

Section: Resultssupporting

confidence: 59%

Dieting alleviates hyperuricemia and organ injuries in uricase-deficient rats via down-regulating cell cycle pathway

Yu,

Wan,

et al. 2023

PeerJ

Self Cite

View full text Add to dashboard Cite

show abstract

“…As reported previously [ 17 , 24 ], Uox -/- rats are apparently healthy. Their serum creatinine and urea are at low levels in the normal ranges, although they are significantly higher than those in wild-type rats.…”

Section: Discussionsupporting

confidence: 82%

“…Considering the mass of the organs, the total uric acid in an organ was calculated by multiplying the uric acid content by its weight [ 24 ]. According to the results shown in Fig 6D , the liver, small intestine, and kidneys were the top three organs in uric acid distribution.…”

Section: Resultsmentioning

confidence: 99%

“…The level of SUA in the Uox -/- rats was higher than that in the reported wild-type rats that were jointly administered with oxonate, and was maintained for at least 130 days. Considering that the uricase deficiency only causes a mild injury in rats [ 24 ], the results suggest that, like humans, the rats are apparently healthy, but vulnerable to renal injury factors.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Uricase-deficient rats with similarly stable serum uric acid to human’s are sensitive model animals for studying hyperuricemia

Gao

Wan

et al. 2022

PLoS ONE

Self Cite

View full text Add to dashboard Cite

The aim of this study was to provide a sensitive model animal for studying hyperuricemia. Male uricase-deficient rats, named Kunming-DY rats, were raised for 130 days, or orally administered with purines and other chemicals. Serum uric acid (SUA) in the animals was assayed, and the UA level in their organs and their 24-h excretion was determined. Genes in the jejunum, ileum, kidney and liver related to UA synthesis and transportation were detected by quantitative RNA sequencing. Uricase-deficient rats have a high level of SUA and are sensitive to xanthine, adenosine, inosine, allopurinol, and alcohol. Besides, the high level of SUA in male uricase-deficient rats was stable, much higher than that in wild-type rats but similar to that in men. The distribution pattern of UA in uricase-deficient rats’ organs was different from that in wild-type rats. The kidney, liver, and small intestine were the top three organs where UA distributed, but the UA in the small intestine, colon, lung, thymus, and brain was less affected by uricase deficiency, indicating that these organs are constitutive distribution organs in UA. The 24-h UA excreted by a uricase-deficient rat was about five times higher than that excreted by a wild-type rat. However, the 24-h UA excreted through feces was not significantly changed. Both the urine volume and UA in uricase-deficient rats significantly increased, and more than 90% of UA was excreted via urine. The expression of xanthine dehydrogenase was not upregulated. Some genes of transporter associated with uric acid excretion in the kidney were significantly regulated, though not sufficient to explain the increase in SUA. In conclusion, male uricase-deficient rats’ UA metabolism is similar to that of men. The elevation of SUA in uricase-deficient rats is caused by uricase deficiency, and uricase-deficient rats are a sensitive model for studying hyperuricemia.

show abstract

Serum Uric Acid as a Diagnostic Biomarker for Rheumatoid Arthritis–Associated Interstitial Lung Disease

Wang

Xiang

et al. 2022

Inflammation

View full text Add to dashboard Cite

Previous studies have suggested a correlation between uric acid (UA) and lung lesion in some diseases. However, it remains unknown whether UA contributes to the lung injury in rheumatoid arthritis (RA). Our study aimed to investigate the clinical value of the UA level in the severity of rheumatoid arthritis–associated interstitial lung disease (RA-ILD). We measured UA in serum and bronchoalveolar lavage fluid (BALF), and UA levels of subjects were compared. As for the role of UA on ILD, we incubated A549 cells with UA and the expression of EMT markers was measured by immunofluorescence staining. The concentrations and messenger RNA expression of IL-1, IL-6, and transforming growth factor-β (TGF-β) were measured by ELISA and RT-PCR, respectively. We observed that serum UA levels in RA were significantly higher than those in controls. And, higher UA was measured in both serum and BALF of patients with RA-ILD, particularly those with interstitial pneumonia (UIP) pattern. Additionally, the correlation of the serum and BALF UA levels with serum KL-6, a biomarker of ILDs, in RA was significant (r = 0.44, p < 0.01; r = 0.43, p < 0.01). And, the negative correlations of UA, in both serum and BALF, with forced vital capacity (r = −0.61, p < 0.01; r = −0.34, p < 0.01) and diffusing capacity for carbon monoxide (r = −0.43, p < 0.01; r = −0.30, p < 0.01) were measured in patients. In the ROC curve analysis, the AUC value of UA for RA-ILD was 0.744 (95% CI: 0.69–0.80; p < 0.01), and the AUC of serum UA for predicting UIP pattern of patients with RA-ILD was 0.845 (95% CI: 0.78–0.91; p < 0.01), which showed the significance of the UA in clinical settings. Also, the in vitro experiment showed that UA induced epithelial-to-mesenchymal transition (EMT) and production of IL-1, IL-6, and TGF-β in A549 cells. Therefore, the elevated UA levels may be a diagnostic marker in RA-ILD, particularly RA-UIP.

show abstract

Uricase deficiency causes mild and multiple organ injuries in rats

Cited by 6 publications

References 20 publications

Dieting alleviates hyperuricemia and organ injuries in uricase-deficient rats via down-regulating cell cycle pathway

Dieting alleviates hyperuricemia and organ injuries in uricase-deficient rats via down-regulating cell cycle pathway

Uricase-deficient rats with similarly stable serum uric acid to human’s are sensitive model animals for studying hyperuricemia

Serum Uric Acid as a Diagnostic Biomarker for Rheumatoid Arthritis–Associated Interstitial Lung Disease

Contact Info

Product

Resources

About