scholarly journals Xanthine Oxidase Inhibitor Febuxostat Exerts an Anti-Inflammatory Action and Protects against Diabetic Nephropathy Development in KK-Ay Obese Diabetic Mice

2019 ◽  
Vol 20 (19) ◽  
pp. 4680 ◽  
Author(s):  
Yu Mizuno ◽  
Takeshi Yamamotoya ◽  
Yusuke Nakatsu ◽  
Koji Ueda ◽  
Yasuka Matsunaga ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Protective Effect ◽  
Xanthine Oxidase ◽  
Glycated Albumin ◽  
Oxidase Inhibitor ◽  
High Serum ◽  
Mrna Levels ◽  
Glomerular Injury ◽  
Xanthine Oxidase Inhibitor ◽  
Ay Mice

Hyperuricemia has been recognized as a risk factor for insulin resistance as well as one of the factors leading to diabetic kidney disease (DKD). Since DKD is the most common cause of end-stage renal disease, we investigated whether febuxostat, a xanthine oxidase (XO) inhibitor, exerts a protective effect against the development of DKD. We used KK-Ay mice, an established obese diabetic rodent model. Eight-week-old KK-Ay mice were provided drinking water with or without febuxostat (15 μg/mL) for 12 weeks and then subjected to experimentation. Urine albumin secretion and degrees of glomerular injury judged by microscopic observations were markedly higher in KK-Ay than in control lean mice. These elevations were significantly normalized by febuxostat treatment. On the other hand, body weights and high serum glucose concentrations and glycated albumin levels of KK-Ay mice were not affected by febuxostat treatment, despite glucose tolerance and insulin tolerance tests having revealed febuxostat significantly improved insulin sensitivity and glucose tolerance. Interestingly, the IL-1β, IL-6, MCP-1, and ICAM-1 mRNA levels, which were increased in KK-Ay mouse kidneys as compared with normal controls, were suppressed by febuxostat administration. These data indicate a protective effect of XO inhibitors against the development of DKD, and the underlying mechanism likely involves inflammation suppression which is independent of hyperglycemia amelioration.

scholarly journals Cardio-renal protective effect of the xanthine oxidase inhibitor febuxostat in the 5/6 nephrectomy model with hyperuricemia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hiroki Omizo ◽  
Yoshifuru Tamura ◽  
Chikayuki Morimoto ◽  
Masaki Ueno ◽  
Yuto Hayama ◽  
...  
Keyword(s):  
Protective Effect ◽  
Xanthine Oxidase ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor

The xanthine oxidase inhibitor febuxostat suppresses development of nonalcoholic steatohepatitis in a rodent model

2015 ◽  
Vol 309 (1) ◽  
pp. G42-G51 ◽  
Author(s):  
Yusuke Nakatsu ◽  
Yasuyuki Seno ◽  
Akifumi Kushiyama ◽  
Hideyuki Sakoda ◽  
Midori Fujishiro ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protective Effect ◽  
Xanthine Oxidase ◽  
Elevated Serum ◽  
Oxidase Inhibitor ◽  
Acid Oxidation ◽  
Purine Nucleotides ◽  
Deficient Diet ◽  
Xanthine Oxidase Inhibitor ◽  
Nonalcoholic Fatty Liver

Xanthine oxidase (XO) is an enzyme involved in the production of uric acid (UA) from purine nucleotides. Numerous recent studies have revealed the likelihood of metabolic syndrome including nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH) to be related to hyperuricemia. However, it remains unclear whether elevated serum UA during the development of NAFLD or NASH is a cause or a consequence of these diseases. In this study, the XO inhibitor febuxostat was administered to two types of NASH model mice. Febuxostat exerted a strong protective effect against NASH development induced by a high-fat diet containing trans fatty acid (HFDT). In contrast, methionine choline-deficient-diet-induced NASH development not accompanied by hyperuricemia showed no UA normalization, suggesting that the ameliorating effect of febuxostat occurs via the normalization of hyperuricemia itself and/or accompanying molecular mechanism(s) such as oxidative stress. In the HFDT-fed mice, hyperuricemia, elevated alanine aminotransferase, and increased Tunnel-positive cells in the liver were normalized by febuxostat administration. In addition, upregulation of fatty acid oxidation-related genes, fibrotic change, and increases in collagen deposition, inflammatory cytokine expressions, and lipid peroxidation in the HFDT-fed mice were also normalized by febuxostat administration. Taken together, these observations indicate that administration of febuxostat has a protective effect against HFDT-induced NASH development, suggesting the importance of XO in its pathogenesis. Thus XO inhibitors are potentially potent therapies for patients with NASH, particularly that associated with hyperuricemia.

scholarly journals The Xanthine Oxidase Inhibitor Febuxostat Suppresses the Progression of IgA Nephropathy, Possibly via Its Anti-Inflammatory and Anti-Fibrotic Effects in the gddY Mouse Model

2018 ◽  
Vol 19 (12) ◽  
pp. 3967 ◽  
Author(s):  
Masa-Ki Inoue ◽  
Takeshi Yamamotoya ◽  
Yusuke Nakatsu ◽  
Koji Ueda ◽  
Yuki Inoue ◽  
...  
Keyword(s):  
Protective Effect ◽  
Xanthine Oxidase ◽  
Iga Nephropathy ◽  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Elevated Serum ◽  
Glomerular Sclerosis ◽  
Mrna Levels ◽  
Xanthine Oxidase Inhibitor ◽  
Serum Iga

Recent clinical studies have demonstrated the protective effect of xanthine oxidase (XO) inhibitors against chronic kidney diseases, although the underlying molecular mechanisms remain unclear. However, to date, neither clinical nor basic research has been carried out to elucidate the efficacy of XO inhibitor administration for IgA nephropathy. We thus investigated whether febuxostat, an XO inhibitor, exerts a protective effect against the development of IgA nephropathy, using gddY mice as an IgA nephropathy rodent model. Eight-week-old gddY mice were provided drinking water with (15 μg/mL) or without febuxostat for nine weeks and then subjected to experimentation. Elevated serum creatinine and degrees of glomerular sclerosis and fibrosis, judged by microscopic observations, were significantly milder in the febuxostat-treated than in the untreated gddY mice, while body weights and serum IgA concentrations did not differ between the two groups. In addition, elevated mRNA levels of inflammatory cytokines such as TNFα, MCP-1, IL-1β, and IL-6, collagen isoforms and chemokines in the gddY mouse kidneys were clearly normalized by the administration of febuxostat. These data suggest a protective effect of XO inhibitors against the development of IgA nephropathy, possibly via suppression of inflammation and its resultant fibrotic changes, without affecting the serum IgA concentration.

Beneficial Effects of Xanthine Oxidase Inhibitor, Topiloxostat, on Experimental Diabetic Neuropathy in Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 549-P
Author(s):  
HIROKI MIZUKAMI ◽  
REMINA KOYAMA ◽  
KAZUHISA TAKAHASHI ◽  
SHO OSONOI ◽  
SAORI OGASAWARA ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Xanthine Oxidase ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor ◽  
Beneficial Effects ◽  
Experimental Diabetic Neuropathy

Allopurinol and Loss of Consciousness in a 78-old Year Man Suffering from Gout

2020 ◽  
Vol 20 (2) ◽  
pp. 253-256 ◽  
Author(s):  
Mahnaz Arian ◽  
Mina AkbariRad ◽  
Ahmad Bagheri Moghaddam ◽  
Abdollah Firoozi ◽  
Mohammad Jami
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Kidney Stones ◽  
Oxidase Inhibitor ◽  
Loss Of Consciousness ◽  
Drug Induced ◽  
Xanthine Oxidase Inhibitor ◽  
Case Presentation ◽  
Maculopapular Rashes ◽  
Reduced State

: Allopurinol is an FDA -Approved xanthine oxidase inhibitor, which is effective in the treatment of gout, hyperuricemia and uremic kidney stones in patients with an increased level of uric acid excretion. Xanthine oxidase acts by converting hypoxanthine and xanthine into uric acid, and therefore its inhibition results in decreased production of uric acid. The most common side effects of this medication are as follows: maculopapular rashes, hives, itching, headache, dizziness, abnormal hair loss, fever and hypersensitivity reaction. Case Presentation: This report represents a case of drug-induced meningitis of a senile man who ended up in the ICU due to the remarkably reduced state of consciousness.

scholarly journals Xanthine oxidase inhibitors are associated with reduced risk of cardiovascular disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hirotaka Saito ◽  
Kenichi Tanaka ◽  
Tsuyoshi Iwasaki ◽  
Akira Oda ◽  
Shuhei Watanabe ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Xanthine Oxidase ◽  
Cardiovascular Events ◽  
Oxidase Inhibitor ◽  
Cardiovascular Risks ◽  
Diabetic Mellitus ◽  
Xanthine Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitors ◽  
Reduced Risk

AbstractAs previous studies have reported finding an association between hyperuricemia and the development of cardiovascular and chronic kidney disease, hyperuricemia is thought to be an independent risk factor for hypertension and diabetic mellitus. However, we have not been able to determine whether the use of xanthine oxidase inhibitors can reduce cardiovascular disease. The present study used the longitudinal data of the Fukushima Cohort Study to investigate the relationship between the use of xanthine oxidase inhibitors and cardiovascular events in patients with cardiovascular risks. During the 3-year period between 2012 and 2014, a total of 2724 subjects were enrolled in the study and followed. A total of 2501 subjects had hypertension, diabetic mellitus, dyslipidemia, or chronic kidney disease, and were identified as having cardiovascular risks. The effects of xanthine oxidase inhibitor use on the development of cardiovascular events was evaluated in these patients using a time to event analysis. During the observational periods (median 2.7 years), the incidence of cardiovascular events was 20.7 in subjects with xanthine oxidase inhibitor and 11.2 (/1000 person-years, respectively) in those without. Although a univariate Cox regression analysis showed that the risk of cardiovascular events was significantly higher in subjects administered xanthine oxidase inhibitors (HR = 1.87, 95% CI 1.19–2.94, p = 0.007), the risk was significantly lower in subjects administered a xanthine oxidase inhibitor after adjustment for covariates (HR = 0.48, 95% CI 0.26–0.91; p = 0.024) compared to those without. Xanthine oxidase inhibitor use was associated with reduced risk of cardiovascular disease in patients with cardiovascular risk factors.

scholarly journals The xanthine oxidase inhibitor oxypurinol does not limit infarct size in a canine model of 40 minutes of ischemia with reperfusion

1988 ◽  
Vol 12 (1) ◽  
pp. 209-217 ◽  
Author(s):  
James M Kinsman ◽  
Charles E Murry ◽  
Vincent J Richard ◽  
Robert B Jennings ◽  
Keith A Reimer
Keyword(s):  
Infarct Size ◽  
Xanthine Oxidase ◽  
Canine Model ◽  
Oxidase Inhibitor ◽  
Xanthine Oxidase Inhibitor
Sign in / Sign up

Export Citation Format

Share Document