Effect and Mechanism of Rhein-praseodymium Complex on Intestinal Uric Acid Excretion in Rats with Renal Injury and Hyperuricemia

Abstract

Background: Hyperuricemia (HUA) is a disease characterized by excessive uric acid production and/or insufficient uric acid excretion caused by abnormal purine metabolism in the human body. Uric acid deposition caused by hyperuricemia can cause complications, such as kidney damage. The current therapeutic drugs for HUA are not very targeted and usually have specific toxic side effects. Objectives: This study aimed to synthesize a compound using rhein and praseodymium, which can effectively help hyperuricemia patients with kidney injury to excrete uric acid through the intestine and preliminarily explore its intestinal excretion mechanism. Methods: The natural active ingredient rhein and rare earth metal praseodymium were used to synthesize Rh-Pr. The possible chemical structure of Rh-Pr was deduced by UV, IR, 1H-NMR, conductivity method, and thermogravity analysis. Adenine (100 mg/kg) and ethambutol hydrochloride (250 mg/kg) were administered by gavage for three weeks to establish the hyperuricemia rat model of renal injury. Serum uric acid (UA), creatinine (Cr), urea nitrogen (BUN), and uric acid concentration in urine and feces were detected by biochemical methods. The protein expression levels of GLUT9, ABCG2, and MRP4 in the jejunum, ileum, and colon of rats were detected by Western Blotting. Results: According to the characterization, the chemical composition formula of the complex is Pr(C15H7O6)3·2H2O. In vivo, activity tests showed that Rh-Pr could enhance the intestinal uric acid excretion level of rats, upregulate the expression of ABCG2 protein in the jejunum and ileum, down-regulate the expression of GLUT9 protein in the ileum and colon, and also had a good recovery effect on serum uric acid, creatinine, and urea nitrogen levels. result: According to the characterization, the chemical composition formula of the complex is Pr(C15H7O6)3·2H2O. The in vivo activity study showed that Rh-Pr could enhance the intestinal uric acid excretion level of rats, up regulate the expression of ABCG2 protein in jejunum and ileum, down regulate the expression of GLUT9 protein in ileum and colon, and also had a good recovery effect on serum uric acid, creatinine and urea nitrogen levels. Conclusion: Rh-Pr is different from other drugs in that it promotes intestinal uric acid excretion and has a renal recovery effect. It reduces the patient's kidney burden and is significant for hyperuricemia patients with kidney injury. conclusion: Rh-Pr has a significant effect on promoting intestinal excretion of uric acid, and its uric acid lowering effect is better than rhein and medicinal charcoal tablets. At the same time, it may have a certain recovery effect on kidney injury. Rare earth metal praseodymium has a synergistic effect on the uric acid lowering activity of Rhein. After complexation, the uric acid lowering activity increases and the metal toxicity decreases,. The mechanism of Rh-Pr promoting intestinal uric acid excretion may be to enhance the expression of ABCG2 in jejunum and ileum, while inhibiting the expression of GLUT9 in ileum and colon.