In Vivo Kinetics of the Uremic Toxin P-Cresyl Sulfate in Mice With Variable Renal Function
In Vivo Kinetics of the Uremic Toxin P-Cresyl Sulfate in Mice With Variable Renal Function
复制标题
尿毒症毒素对甲酚硫酸盐在肾功能可变小鼠体内的体内动力学
DOI：
10.1111/1744-9987.12185
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发表时间：
2014
影响因子：
1.9
通讯作者：
Zhang Ruiyan
中科院分区：
文献类型：
--
作者：
Ni Jingwei;Zhang Wenli;Zhu Zhengbin;Zhu Jinzhou;Du Run;Jing Yajun;Lu Lin;Zhang Ruiyan
尿毒症毒素如硫酸对甲苯酯（PCS）与慢性肾病（CKD）患者死亡率增加相关，但由于缺乏标准动物模型，体内PCS毒性研究有限。为了建立这样一个模型，我们测量了PCS在不同肾功能小鼠中的药代动力学。对5/6肾切除术（CRF）、单侧肾切除术（UNX）或未手术（对照）的雄性Balb/c小鼠给予PCS（po，50 mg/kg）。随着时间的推移收集血液样品，并测量血浆PCS浓度。在4小时内，CRF小鼠血浆中PCS（63.28 ± 2.76 mg/L）显著高于UNX小鼠（3.11 ± 0.64 mg/L）和对照组（0.39 ± 0.12 mg/L）。CRF小鼠的PCS半衰期最长（12.07 ± 0.12 h），UNX小鼠为0.79 ± 0.04 h，对照小鼠为0.48 ± 0.02 h。然而，CRF小鼠中可能存在额外的尿毒症毒素沿着PCS，对照小鼠中PCS快速清除，这表明UNX小鼠是研究毒性的更好PCS模型。
Uremic toxins such as p‐cresyl sulfate (PCS) are associated with increased mortality for chronic kidney disease (CKD) patients, but in vivo PCS toxicity studies are limited due to the lack of a standard animal model. To establish such a model, we measured the pharmacokinetics of PCS in mice with variable renal function. Male Balb/c mice subjected to 5/6 nephrectomy (CRF), unilateral nephrectomy (UNX), or no surgery (controls) were given PCS (po, 50 mg/kg). Blood samples were collected over time and plasma PCS concentrations were measured. Over 4 h, PCS was significantly higher in the plasma of CRF mice (63.28 ± 2.76 mg/L), compared to UNX mice (3.11 ± 0.64 mg/L) and controls (0.39 ± 0.12 mg/L). The PCS half‐life was greatest in CRF mice (12.07 ± 0.12 h), compared to 0.79 ± 0.04 h in UNX mice and 0.48 ± 0.02 h in control mice. However, the potential presence of additional uremic toxins along with PCS in CRF mice and rapid PCS clearance in control mice suggest that the UNX mouse would be a better PCS model to study toxicity.