Anti-Hyperuricemic Effects of Astaxanthin by Regulating Xanthine Oxidase, Adenosine Deaminase and Urate Transporters in Rats

Abstract

This study was designed to investigate the effects and underlying mechanisms of Astaxanthin (AST) on high-fructose-induced hyperuricemia (HUA) from the perspectives of the uric acid (UA) synthesis and excretion in rat models. Following six weeks of a 10% fructose diet, the level of serum UA effectively decreased in the AST groups as compared to the model group. The enzymatic activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) were significantly inhibited, and the mRNA expression levels of XOD and ADA significantly decreased after the AST administration. These results suggested that the AST reduced UA synthesis by inhibiting the mRNA expressions and enzyme activities of XOD and ADA, thereby contributing to HUA improvement. On the hand, the relative expressions of the mRNA and protein of kidney reabsorption transport proteins (GLUT9 and URAT1) were significantly down-regulated by AST, while that of the kidney secretion proteins (OAT1, OAT3 and ABCG2) were significantly up-regulated by AST. These results indicated that the AST promoted UA excretion by regulating the urate transport proteins, and thus alleviated HUA. This study suggested that the AST could serve as an effective alternative to traditional medicinal drugs for the prevention of fructose-induced HUA.

Ellagic Acid Exerts Beneficial Effects on Hyperuricemia by Inhibiting Xanthine Oxidase and NLRP3 Inflammasome Activation

“…However, if blood levels of UA are high, UA is crystallized and deposited as monosodium urate (MSU) in the joints and tissues and is closely correlated with the occurrence of gout and inflammation. MSU can trigger the production of the pro-inflammatory mediators nuclear factor-kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) via Toll-like receptor 4 (TLR4) . In addition, both ROS and MSU are well-known activators of the nucleotide-binding oligomerization domain-like receptor family containing pyrin domain 3 (NLRP3) inflammasome .…”

“…MSU can trigger the production of the pro-inflammatory mediators nuclear factor-kappa B (NF-κB) and tumor necrosis factor-alpha (TNF-α) via Toll-like receptor 4 (TLR4). 11 In addition, both ROS and MSU are well-known activators of the nucleotide-binding oligomerization domain-like receptor family containing pyrin domain 3 (NLRP3) inflammasome. 12 The NLRP3 inflammasome serves as a platform for the activation of interleukin (IL)-18 and IL-1β secretion through the stimulation of apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) and cysteinyl aspartate specific proteinase 1 (caspase-1).…”

Anti-Inflammatory and Anti-Hyperuricemic Effects of Chrysin on a High Fructose Corn Syrup-Induced Hyperuricemia Rat Model via the Amelioration of Urate Transporters and Inhibition of NLRP3 Inflammasome Signaling Pathway

“…On the other hand, the uric acid excretion transporters ABCG2 and OAT1 are responsible for regulating uric acid excretion via secreting uric acid into the urethra [ 43 ]. Previous studies showed that six weeks of treatment of a 10% fructose diet altered the urate transporter regulation and increased the uric acid serum level [ 44 ]. Moreover, many natural extracts have been explored for efficacy using animal models of hyperuricemia such as quercetin [ 36 ], resveratrol [ 45 ], fucoxanthin [ 46 ], green tea polyphenols [ 47 ], and longan extract [ 48 ], which can inhibit the reabsorption of uric acid by regulating uric acid-related transporters.…”

Drug Transporters in the Kidney: Perspectives on Species Differences, Disease Status, and Molecular Docking

“…Thus, the levels of renal transporters should attract clinician attentions. In animal models, the OAT1/3, OCT2, and BCRP expressions are decreased under the pathological condition, whereas MDR1 and MRP2/4 expressions are not affected by hyperuricemia (Nishizawa et al, 2019;Le et al, 2020). A growing number of studies have reported that OAT1/3, OCT2, and BCRP are involved in urate efflux from epithelial cells to urine (Taniguchi et al, 2021), and these transporters have been extensively studied in the hyperuricemia.…”