Uric acid accumulation in the kidney triggers mast cell degranulation and aggravates renal oxidative stress

Zhang, Mingkang; Cui, Ruirui; Zhou, Yan; Yue, Ma; Jin, Yongxing; Gou, Xueyan; Yang, Jinru; Wu, Xin’an

doi:10.1016/j.tox.2022.153387

Cited by 10 publications

(6 citation statements)

References 41 publications

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“…The mice were randomly divided into 7 groups: normal group (Normal), diseased group (Diseased), allopurinol group (Alp), hesperitin group (Hsp), low-dose Hsp-Cu(II) complex group (LHC), mediumdose Hsp-Cu(II) complex group (MHC), and high-dose Hsp-Cu(II) complex group (HHC). Mice except the Normal group were administered intragastrically with oteracil potassium [200 mg/kg body weight (BW)] and hypoxanthine (200 mg/kg) for 2 weeks to establish the HUA diseased mice [34]. Then Alp group mice were given Alp (10 mg/kg), Hsp group mice were given Hsp (60 mg/kg), and the LHC, MHC, and HHC groups mice were given 30, 60, and 120 mg/kg Hsp-Cu(II) complex for 22 days, respectively.…”

Section: Animalsmentioning

confidence: 99%

“…The whole blood, liver, and kidney were collected, and the organs were weighed. The organ index was calculated based on a previous report [34]. The blood of the mice was centrifuged at 6000× g for 15 min to collect the supernatant and stored at −80 • C. One part of the kidneys was soaked in 4% paraformaldehyde for kidney tissue observation.…”

Section: Animalsmentioning

confidence: 99%

“…The blood of the mice was centrifuged at 6000× g for 15 min to collect the supernatant and stored at −80 • C. One part of the kidneys was soaked in 4% paraformaldehyde for kidney tissue observation. The rest of the kidney and liver were stored at −80 • C for follow-up experiments [34].…”

Section: Animalsmentioning

confidence: 99%

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Hesperitin-Copper(II) Complex Regulates the NLRP3 Pathway and Attenuates Hyperuricemia and Renal Inflammation

Peng,

Liu,

et al. 2024

Foods

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Background: Hyperuricaemia (HUA) is a disorder of purine metabolism in the body. We previously synthesized a hesperitin (Hsp)-Cu(II) complex and found that the complex possessed strong uric acid (UA)-reducing activity in vitro. In this study we further explored the complex’s UA-lowering and nephroprotective effects in vivo. Methods: A mouse with HUA was used to investigate the complex’s hypouricemic and nephroprotective effects via biochemical analysis, RT-PCR, and Western blot. Results: Hsp-Cu(II) complex markedly decreased the serum UA level and restored kidney tissue damage to normal in HUA mice. Meanwhile, the complex inhibited liver adenosine deaminase (ADA) and xanthine oxidase (XO) activities to reduce UA synthesis and modulated the protein expression of urate transporters to promote UA excretion. Hsp-Cu(II) treatment significantly suppressed oxidative stress and inflammatory in the kidney, reduced the contents of cytokines and inhibited the activation of the nucleotide-binding oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory pathway. Conclusions: Hsp-Cu(II) complex reduced serum UA and protected kidneys from renal inflammatory damage and oxidative stress by modulating the NLRP3 pathway. Hsp-Cu(II) complex may be a promising dietary supplement or nutraceutical for the therapy of hyperuricemia.

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Section: Animalsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

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Hesperitin-Copper(II) Complex Regulates the NLRP3 Pathway and Attenuates Hyperuricemia and Renal Inflammation

Peng,

Liu,

et al. 2024

Foods

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“…Recent experimental studies have shown that the internalization of UA increases oxidative stress within cells [66]. In human epithelial tubular cells, UA causes increased free radicals and oxidative stress via NADPH oxidase and induces inflammation [67,68].…”

Section: Uric Acidmentioning

confidence: 99%

Non-Haemodynamic Mechanisms Underlying Hypertension-Associated Damage in Target Kidney Components

Russo¹,

Bussalino

Macciò

et al. 2023

IJMS

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Arterial hypertension (AH) is a global challenge that greatly impacts cardiovascular morbidity and mortality worldwide. AH is a major risk factor for the development and progression of kidney disease. Several antihypertensive treatment options are already available to counteract the progression of kidney disease. Despite the implementation of the clinical use of renin–angiotensin aldosterone system (RAAS) inhibitors, gliflozins, endothelin receptor antagonists, and their combination, the kidney damage associated with AH is far from being resolved. Fortunately, recent studies on the molecular mechanisms of AH-induced kidney damage have identified novel potential therapeutic targets. Several pathophysiologic pathways have been shown to play a key role in AH-induced kidney damage, including inappropriate tissue activation of the RAAS and immunity system, leading to oxidative stress and inflammation. Moreover, the intracellular effects of increased uric acid and cell phenotype transition showed their link with changes in kidney structure in the early phase of AH. Emerging therapies targeting novel disease mechanisms could provide powerful approaches for hypertensive nephropathy management in the future. In this review, we would like to focus on the interactions of pathways linking the molecular consequences of AH to kidney damage, suggesting how old and new therapies could aim to protect the kidney.

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“…Part of uric acid remains in the blood while the rest is eliminated by the kidneys or the gastrointestinal tract [ 2 ]. The levels of uric acid in the blood may increase due to increased endogenous production, difficulties in elimination, and interference with the use of certain medications [ 3 , 4 ], or even through the ingestion of foods rich in purines, such as animal protein, barley, soft drinks, distilled beverages, and high-fructose beverages [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Hyperuricemic, Anti-Arthritic, Hemolytic Activity and Therapeutic Safety of Glycoconjugated Triazole-Phthalimides

Silva,

Aires,

Cunha

et al. 2023

Biomedicines

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Hyperuricemia, the metabolic alteration that leads to gout or gouty arthritis, is increasing worldwide. Glycoconjugated triazole-phthalimides show potent anti-inflammatory activity. The aim of this study was to evaluate the anti-hyperuricemia effect of glycoconjugated triazole-phthalimides. To develop hyperuricemia, groups of mice received orally potassium oxonate (250 mg/kg) for 7 days, and F2, F3 and F4 glycoconjugated triazole-phthalimides (20 mg/kg), allopurinol (300 mg/kg), and 1% carboxymethylcellulose; indomethacin (2 and 4 mg/kg) was the positive control for anti-arthritic effect. Genotoxic and mutagenic effects were evaluated by the comet and micronucleus assays, respectively. The hemolytic action of the compounds was evaluated. Phthalimides F2, F3 and F4 significantly reduced the levels of serum uric acid, creatinine and urea in hyperuricemic animals. In addition, the compounds were efficient in reducing protein denaturation in a dose-dependent manner. In an interesting way, the histopathological analysis of kidneys from groups treated with F2, F3 and F4 showed a glomerular architecture, with the Bowman’s capsule and renal tubules having a normal appearance and without inflammatory changes. Also, F2 and F4 showed a small increase in micronuclei, indicating a low mutagenic effect, whilst by comet assay only, we could infer that F4 affected the frequency and damage index, thus indicating a very small genotoxic action. Similarly, the phthalimides showed a low degree of erythrocyte hemolysis (<3%). Our data demonstrate that the new glycoconjugate triazole-phthalimides have potential to treat hyperuricemia and its secondary complications, such as gouty arthritis, with a low to non-significant rate of erythrocytes hemolysis, genotoxicity and mutagenicity making these molecules strong candidates as pharmaceutical agents for treatment requiring uric-acid-lowering therapy.

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Uric acid accumulation in the kidney triggers mast cell degranulation and aggravates renal oxidative stress

Cited by 10 publications

References 41 publications

Hesperitin-Copper(II) Complex Regulates the NLRP3 Pathway and Attenuates Hyperuricemia and Renal Inflammation

Hesperitin-Copper(II) Complex Regulates the NLRP3 Pathway and Attenuates Hyperuricemia and Renal Inflammation

Non-Haemodynamic Mechanisms Underlying Hypertension-Associated Damage in Target Kidney Components

Anti-Hyperuricemic, Anti-Arthritic, Hemolytic Activity and Therapeutic Safety of Glycoconjugated Triazole-Phthalimides

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