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首页> 外文期刊>Journal of Cachexia, Sarcopenia and Muscle >Febuxostat improves outcome in a rat model of cancer cachexia
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Febuxostat improves outcome in a rat model of cancer cachexia

机译：非布索坦可改善癌症恶病质大鼠模型的结果

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AbstractBackgroundActivity of xanthine oxidase is induced in cancer cachexia, and its inhibition by allopurinol or oxypurinol improves survival and reduces wasting in the Yoshida hepatoma cancer cachexia model. Here, we tested the effects of the second-generation xanthine oxidase inhibitor febuxostat compared with placebo in the same model as used previously by our group.MethodsWistar rats (~200 g) were treated daily with febuxostat at 5 mg/kg/day or placebo via gavage for a maximum of 17 days. Weight change, quality of life, and body composition were analysed. After sacrifice, proteasome activity in the gastrocnemius muscle was measured. Muscle-specific proteins involved in metabolism were analysed by western blotting.ResultsTreatment of the tumour-bearing rats with febuxostat led to a significantly improved survival compared with placebo (hazard ratio: 0.45, 95% confidence interval: 0.22–0.93, P = 0.03). Loss of body weight was reduced (−26.3 ± 12.4 g) compared with placebo (−50.2 ± 2.1 g, P  0.01). Wasting of lean mass was attenuated (−12.7 ± 10.8 g) vs. placebo (−31.9 ± 2.1 g, P  0.05). While we did not see an effect of febuxostat on proteasome activity at the end of the study, the pAkt/Akt ratio was improved by febuxostat (0.94 ± 0.09) vs. placebo (0.41 ± 0.05, P  0.01), suggesting an increase in protein synthesis.ConclusionsFebuxostat attenuated cachexia progression and improved survival of tumour-bearing rats.
机译：摘要黄嘌呤氧化酶的活性在恶病质中被诱导，其被别嘌呤醇或氧嘌呤醇的抑制作用提高了存活率并减少了吉田肝癌恶病质模型的浪费。在这里，我们在与我们小组先前使用的模型相同的模型中测试了第二代黄嘌呤氧化酶抑制剂非布司他与安慰剂的作用。方法Wistar大鼠（〜200μg）每天用5μmg/ kg /天的非布司他或安慰剂治疗通过管饲法最多可以进行17天。分析体重变化，生活质量和身体组成。处死后，测量腓肠肌中的蛋白酶体活性。结果：与非安慰剂相比，用非布司他治疗荷瘤大鼠可显着改善存活率（危险比：0.45，95％置信区间：0.22-0.93，P = 0.03） 。与安慰剂相比（-50.2±2.1±g，P ＜0.01），体重减轻了（-26.3±12.4g）。与安慰剂相比，瘦肉的浪费减少了（-12.7±10.8μg）（-31.9±2.1μg，P <0.05）。虽然在研究结束时我们没有看到非布索坦对蛋白酶体活性的影响，但与安慰剂相比，非布索坦（0.94±0.09）改善了pAkt / Akt比（0.41±0.05，P <0.01），表明结论：非布司他减缓恶病质的进展并改善荷瘤大鼠的存活率。

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