ArticlePhysiological reports2017
Renoprotective effect of topiroxostat via antioxidant activity in puromycin aminonucleoside nephrosis rats.
Article in Physiological reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Comparative effects of topiroxostat and febuxostat on arterial properties in hypertensive patients with hyperuricemia.Journal of clinical hypertension (Greenwich, Conn.) · 2021Trial
- Nicorandil protects podocytes via modulation of antioxidative capacity in acute puromycin aminonucleoside-induced nephrosis in rats.American journal of physiology. Renal physiology · 2023Article
- Increased Lung Uric Acid Deteriorates Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2021Article
- Shensu IV prevents glomerular podocyte injury in nephrotic rats via promoting lncRNA H19/DIRAS3-mediated autophagy.Bioscience reports · 2021Article
- Xanthine Oxidoreductase Inhibitors.Handbook of experimental pharmacology · 2021Article
- The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors.Oxidative medicine and cellular longevity · 2021Review
- Research Advances in the Mechanisms of Hyperuricemia-Induced Renal Injury.BioMed research international · 2020Review
- Gender-specific association between uric acid level and chronic kidney disease in the elderly health checkup population in China.Renal failure · 2019Observational
- The effects of xanthine oxidase inhibitor in patients with chronic heart failure complicated with hyperuricemia: a prospective randomized controlled clinical trial of topiroxostat vs allopurinol-study protocol.Clinical and experimental nephrology · 2018Article
- Renoprotective effect of topiroxostat via antioxidant activity in puromycin aminonucleoside nephrosis rats.Physiological reports · 2017Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Topiroxostat is a novel inhibitor of xanthine oxidase, and is postulated to exert a renoprotective effect. Puromycin aminonucleoside nephrosis (PAN) is a rat model of minimal change nephrotic syndrome. In this study, we examined whether topiroxostat ameliorates the kidney injury in PAN rats that was induced by a single intraperitoneal injection of PA (100 mg/kg body weight). Rats were divided into four groups: control rats, PAN rats, control rats treated with topiroxostat (1.0 mg/kg/day), and PAN rats treated with topiroxostat. Topiroxostat significantly reduced the amount of uric acid in the kidney cortex, while serum UA concentration remained unaffected by this treatment. Urinary protein excretion decreased significantly on day 10 in PAN rats upon topiroxostat treatment. Podocyte injury in PAN rats, as indicated by the reduction in WT-1-positive cell numbers and podocin immunoreactivity and foot process effacement, was partially yet significantly alleviated with topiroxostat treatment. In the kidney cortex, the increase in oxidative stress markers such as nitrotyrosine and 8-hydroxy-2-deoxyguanosine (8-OHdG) and the enhanced expressions of xanthine oxidase and NADPH oxidase 4 (NOX4) in PAN rats were significantly ameliorated by topiroxostat. Using cultured podocytes NOX4 expression was upregulated by adding 12 mg/dL UA into the culture medium. These results suggest that topiroxostat ameliorates proteinuria and kidney injury in PAN rats by lowering oxidative stress and tissue UA concentration. The renoprotective effects of topiroxostat could be attributed to its potential to inhibit xanthine oxidase and NOX4 in concert with suppression of intracellular UA production.
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