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壳聚糖-铁(III)复合物作为尿毒症大鼠的磷酸盐螯合剂:一种新的治疗选择。

Chitosan-Fe (III) Complex as a Phosphate Chelator in Uraemic Rats: A Novel Treatment Option.

机构信息

Division of Clinical Medicine of the Federal University of Juiz de Fora, Juiz de Fora, Brazil.

Interdisciplinary Center for Laboratory Animal Studies (NIDEAL), Center for Reproductive Biology, Federal University of Juiz de Fora, Juiz de Fora, Brazil.

出版信息

Basic Clin Pharmacol Toxicol. 2018 Jan;122(1):120-125. doi: 10.1111/bcpt.12849. Epub 2017 Aug 10.

Abstract

Phosphate retention and hyperphosphataemia are associated with increased mortality in patients with chronic kidney disease (CKD). We tested the use of cross-linked iron chitosan III (CH-FeCl) as a potential phosphate chelator in rats with CKD. We evaluated 96 animals, divided equally into four groups (control, CKD, CH-FeCl and CKD/CH-FeCl), over 7 weeks. We induced CKD by feeding animals an adenine-enriched diet (0.75% in the first 4 weeks and 0.1% in the following 3 weeks). We administered 30 mg/kg daily of the test polymer, by gavage, from the third week until the end of the study. All animals received a diet supplemented with 1% phosphorus. Uraemia was confirmed by the increase in serum creatinine in week 4 (36.24 ± 18.56 versus 144.98 ± 22.1 μmol/L; p = 0.0001) and week 7 (41.55 ± 22.1 versus 83.98 ± 18.56 μmol/L; p = 0.001) in CKD animals. Rats from the CKD group treated with CH-FeCl had a 54.5% reduction in serum phosphate (6.10 ± 2.23 versus 2.78 ± 0.55 mmol/L) compared to a reduction of 25.6% in the untreated CKD group (4.75 ± 1.45 versus 3.52 ± 0.74 mmol/L, p = 0.021), between week 4 and week 7. At week 7, renal function in both CKD groups was similar (serum creatinine: 83.98 ± 18.56 versus 83.10 ± 23.87 μmol/L, p = 0.888); however, the CH-FeCl-treated rats had a reduction in phosphate overload measured by fractional phosphate excretion (FEPi) (0.71 ± 0.2 versus 0.4 ± 0.16, p = 0.006) compared to the untreated CKD group. Our study demonstrated that CH-FeCl had an efficient chelating action on phosphate.

摘要

磷酸盐潴留和高磷血症与慢性肾脏病(CKD)患者的死亡率增加有关。我们测试了交联铁壳聚糖 III(CH-FeCl)作为 CKD 大鼠潜在的磷酸盐螯合剂的用途。我们评估了 96 只动物,平均分为四组(对照组、CKD 组、CH-FeCl 组和 CKD/CH-FeCl 组),持续 7 周。我们通过给动物喂食富含腺嘌呤的饮食(前 4 周为 0.75%,接下来 3 周为 0.1%)来诱导 CKD。从第 3 周开始,我们每天给 30mg/kg 的试验聚合物进行管饲,直到研究结束。所有动物均接受添加 1%磷的饮食。第 4 周(36.24 ± 18.56 与 144.98 ± 22.1 μmol/L;p = 0.0001)和第 7 周(41.55 ± 22.1 与 83.98 ± 18.56 μmol/L;p = 0.001)时血清肌酐的增加证实了尿毒症,CKD 动物。与未治疗的 CKD 组相比,用 CH-FeCl 治疗的 CKD 组的血清磷酸盐降低了 54.5%(6.10 ± 2.23 与 2.78 ± 0.55 mmol/L),而未治疗的 CKD 组降低了 25.6%(4.75 ± 1.45 与 3.52 ± 0.74 mmol/L,p = 0.021),在第 4 周到第 7 周之间。第 7 周时,两组 CKD 动物的肾功能相似(血清肌酐:83.98 ± 18.56 与 83.10 ± 23.87 μmol/L,p = 0.888);然而,与未治疗的 CKD 组相比,用 CH-FeCl 治疗的大鼠的磷排泄分数(FEPi)测量的磷过载减少(0.71 ± 0.2 与 0.4 ± 0.16,p = 0.006)。我们的研究表明,CH-FeCl 对磷酸盐具有有效的螯合作用。

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