Effects of Uric Acid on Hearts of Rats with Chronic Kidney Disease

Abstract

Aims: To study the effects of uric acid on cardiac lesions and its possible mechanism by establishing an early-stage CKD animal model with hyperuricemia. Allopurinol was used to see whether it could reduce cardiac lesions. Methods: The experimental rats were randomly divided into 4 groups (n = 15): Group A (sham-operative group), Group B (CKD group), Group C (CKD with hyperuricemia group), Group D (CKD with hyperuricemia + allopurinol group). After 16 weeks, the rats were sacrificed and blood samples were collected for detection of Scr, SUA, hs-CRP and IL-6. Kidney and heart tissues were pathologically examined. The collagen I of heart tissues was examined by immunohistochemistrical methods. Results: Obvious pathological changes could be observed in Group C. However, compared to Group C, the pathological changes in Group D were lighter. The proportion of collagen I positive area (PCIPA) in Group C was significantly higher than that in Group A, B and D. Univariate analysis showed that the SUA level had a significant positive correlation with PCIPA in myocardium. IL-6 and hs-CRP levels in Group C were significantly higher than in Group A, B and D. Univariate analysis showed that the SUA level had a significant positive correlation with IL-6 and hs-CRP, and PCIPA in myocardium had a significant positive correlation with hs-CRP and IL-6 levels. Conclusions: There were obvious cardiac lesions in early-stage CKD rats with hyperuricemia, and the severity of cardiac lesions was positively related to the level of SUA. Micro-inflammation might be one mechanism causing cardiac lesions. Allopurinol could alleviate cardiac lesions in early-stage CKD rats by lowering the SUA level, which, in turn, could reduce the severity of micro-inflammation.

Uric acid regulates NLRP3/IL-1β signaling pathway and further induces vascular endothelial cells injury in early CKD through ROS activation and K+ efflux

“…The animal model was established as described [17]. Briefly, 20 male Sprague-Dawley rats (220~250 g, 6~8 weeks old) were obtained from Hunan Slac Jingda Experimental Animal Co. Ltd. (Changsha, China) and kept in the animal experimental center of the First Affiliated Hospital of Hunan Normal University (Changsha, China).…”

Negative correlation between serum uric acid and kidney URAT1 mRNA expression caused by resveratrol in rats

“…Allopurinol is a competitive inhibitor of xanthine oxidase, which reduces the generation of UA. As a traditional UA‐lowering drug, allopurinol is routinely used to treat gout . However, adverse effects limit its effectiveness .…”

Uric acid promotes myocardial infarction injury via activating pyrin domain-containing 3 inflammasome and reactive oxygen species/transient receptor potential melastatin 2/Ca2+pathway

“…However, this method is not enough to prevent the further deterioration of cardiac function and might further cause serious problems such as ischemia–reperfusion injury. It has been reported that high uric acid (UA) is closely related with cardiovascular disease, and the severity of cardiac lesions is positively related to the level of serum UA [ 1 , 2 ]. Meanwhile, UA can induce the endothelial dysfunction, and this effect might associate with decreased intracellular ATP, mitochondrial alterations [ 3 , 4 ].…”