Uricosuric agents decrease the plasma urate level in rats by concomitant treatment with topiroxostat, a novel xanthine oxidoreductase inhibitor

2015 ◽  
Vol 68 (1) ◽  
pp. 76-83 ◽  
Author(s):  
Tetsuya Taniguchi ◽  
Naoki Ashizawa ◽  
Koji Matsumoto ◽  
Takashi Iwanaga ◽  
Kazuhiro Saitoh
Keyword(s):  
Concomitant Treatment ◽  
Xanthine Oxidoreductase ◽  
Uricosuric Agents ◽  
Plasma Urate ◽  
Xanthine Oxidoreductase Inhibitor

scholarly journals Xanthine oxidoreductase inhibitor topiroxostat ameliorates podocyte injury by inhibiting the reduction of nephrin and podoplanin

Nefrología ◽  
2021 ◽  
Author(s):  
Ying Zhang ◽  
Yoshiyasu Fukusumi ◽  
Mutsumi Kayaba ◽  
Takashi Nakamura ◽  
Ryusuke Sakamoto ◽  
...  
Keyword(s):  
Xanthine Oxidoreductase ◽  
Podocyte Injury ◽  
Xanthine Oxidoreductase Inhibitor

scholarly journals Influence of xanthine oxidoreductase inhibitor, topiroxostat, on body weight of diabetic obese mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takashi Nakamura ◽  
Mai Nampei ◽  
Takayo Murase ◽  
Etsuko Satoh ◽  
Seigo Akari ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Ketone Body ◽  
The Body ◽  
Xanthine Oxidoreductase ◽  
Diabetic Mellitus ◽  
Triglyceride Content ◽  
Xanthine Oxidoreductase Inhibitor ◽  
Single Regression ◽  
Muscle Triglyceride

AbstractPlasma xanthine oxidoreductase (XOR) activity is high in metabolic disorders such as diabetic mellitus, obesity, or overweight. Thus, this study investigated whether the XOR inhibitor, topiroxostat, affected body weight. Male db/db mice were fed standard diets with or without topiroxostat for 4 weeks. Body weight and food intake were constantly monitored, along with monitoring plasma biochemical markers, including insulin and XOR activity. Additionally, hepatic hypoxanthine and XOR activity were also documented. Single regression analysis was performed to determine the mechanism. Topiroxostat treatment suppressed weight gain relative to the vehicle without any impact on food intake. However, the weight of fat pads and hepatic and muscle triglyceride content did not change. Topiroxostat decreased the plasma uric acid and increased hepatic hypoxanthine in response to the inhibition of XOR activity. Plasma ketone body and free fatty acid were also increased. Moreover, fat weight was weakly associated with plasma XOR activity in the diabetic state and was negatively associated with ketone body by topiroxostat. These results suggested that topiroxostat amplified the burning of lipids and the salvage pathway, resulting in predisposing the body toward catabolism. The inhibition of plasma XOR activity may contribute to weight loss.

Anti‐hyperuricemia activity and toxicity prediction of a novel xanthine oxidoreductase inhibitor

2019 ◽  
Vol 34 (2) ◽  
Author(s):  
Liping Zhou ◽  
Baxiong Wei ◽  
Lvying Wu ◽  
Jing Li ◽  
Bin Zhu ◽  
...  
Keyword(s):  
Xanthine Oxidoreductase ◽  
Toxicity Prediction ◽  
Xanthine Oxidoreductase Inhibitor

Xanthine crystals induced by topiroxostat, a xanthine oxidoreductase inhibitor, in rats, cause transitional cell tumors

2014 ◽  
Vol 88 (4) ◽  
pp. 1035-1042 ◽  
Author(s):  
Takeo Shimo ◽  
Mitsuyoshi Moto ◽  
Naoki Ashizawa ◽  
Koji Matsumoto ◽  
Takashi Iwanaga ◽  
...  
Keyword(s):  
Transitional Cell ◽  
Xanthine Oxidoreductase ◽  
Xanthine Oxidoreductase Inhibitor ◽  
Transitional Cell Tumors

scholarly journals Renoprotective effect of the xanthine oxidoreductase inhibitor topiroxostat on adenine-induced renal injury

2016 ◽  
Vol 310 (11) ◽  
pp. F1366-F1376 ◽  
Author(s):  
Atsuko Kamijo-Ikemori ◽  
Takeshi Sugaya ◽  
Chihiro Hibi ◽  
Takashi Nakamura ◽  
Takayo Murase ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Serum Creatinine ◽  
Renal Injury ◽  
High Dose ◽  
Xanthine Oxidoreductase ◽  
Fatty Acid Binding ◽  
Injury Model ◽  
Tubulointerstitial Damage ◽  
Xanthine Oxidoreductase Inhibitor ◽  
Group Serum

The aim of the present study was to reveal the effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice ( n = 24) were fed a 0.2% (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal dysfunction was confirmed, and the mice were divided into the following four groups: the adenine group was given only the diet containing adenine, and the Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to adenine for another 2 wk. After withdrawal of the adenine diet, each medication was continued for 2 wk. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels, and renal XOR activity were significantly attenuated in the kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group. Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the Top-H group were significantly lower than those in the Feb group. Urinary excretion of L-FABP in both the Top-H and Top-L groups was significantly lower than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in an adenine-induced renal injury model.

Study on toxicological aspects of crystal-mediated nephrotoxicity induced by FYX-051, a xanthine oxidoreductase inhibitor, in rats

2011 ◽  
Vol 34 (2) ◽  
pp. 192-198 ◽  
Author(s):  
Takeo Shimo ◽  
Mitsuyoshi Moto ◽  
Naoki Ashizawa ◽  
Kazuhiko Oba ◽  
Osamu Nagata
Keyword(s):  
Xanthine Oxidoreductase ◽  
Xanthine Oxidoreductase Inhibitor
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