Oral charcoal adsorbent (AST-120) prevents progression of cardiac damage in chronic kidney disease through suppression of oxidative stress
Oral charcoal adsorbent (AST-120) prevents progression of cardiac damage in chronic kidney disease through suppression of oxidative stress
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DOI：
10.1093/ndt/gfp007
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发表时间：
2009-07-01
影响因子：
6.1
通讯作者：
Fukagawa, Masafumi
中科院分区：
文献类型：
--
作者：
Fujii, Hideki;Nishijima, Fuyuhiko;Fukagawa, Masafumi
方法.雄性刘易斯大鼠在8周龄时给予阿霉素，并在12周龄时切除右肾。从14周龄开始，每天用AST-120处理大鼠（n = 8）或不处理（对照组，n = 8）。34周龄时处死大鼠，进行尿、血生化检查及心脏组织学分析。在14周龄时，对照组和AST-120组之间的血压、肾功能（肌酐清除率：1.54 +/- 0.28 mL/min vs 1.60 +/- 0.22 mL/min）、氧化应激标志物或其他生化数据无显著差异。在34周时，尽管血压和肾功能相似（肌酐清除率：0.78 +/- 0.46 mL/min vs 0.75 +/- 0.54 mL/min），但AST-120组的IS血清浓度和8-羟基脱氧鸟苷（8-OHdG）、丙烯醛和IS的尿排泄量显著低于对照组。实验AST-120组的心脏体积、左心室体积和心脏纤维化明显小于对照组。免疫组织化学分析显示，8-OHdG-和丙烯醛阳性心肌细胞的数量和心肌和血管周围纤维化的程度，AST-120管理改善。心肌纤维化评分与8-OHdG-（r = 0.848，P < 0.001）和丙烯醛阳性（r = 0.812，P < 0.001）细胞评分显著相关。血管周围纤维化评分与8-OHdG-（r = 0.906，P < 0.0001）和丙烯醛阳性（r = 0.789，P < 0.001）细胞评分也显著相关。氧化应激在慢性肾脏病心肌肥厚和纤维化的发展中起着关键作用。AST-120可抑制CKD中的氧化应激并减少心脏损伤。
Methods. Male Lewis rats were administered adriamycin at 8 weeks of age, and the right kidney was removed at 12 weeks of age. From 14 weeks of age, the rats were treated daily with AST-120 (n = 8) or were untreated (control group, n = 8). At 34 weeks of age, the rats were killed and urinary and blood biochemical tests as well as cardiac histological analyses were performed.Results. At 14 weeks of age, there were no significant differences in blood pressure, renal function (creatinine clearance: 1.54 +/- 0.28 mL/min versus 1.60 +/- 0.22 mL/min), oxidative stress markers or other biochemical data between the control and AST-120 groups. At 34 weeks, despite similar blood pressure and renal function (creatinine clearance: 0.78 +/- 0.46 mL/min versus 0.75 +/- 0.54 mL/min), serum concentrations of IS and urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), acrolein and IS were significantly lower in the AST-120 group than in the control group. Heart volume, left ventricular volume and cardiac fibrosis were significantly smaller in the experimental AST-120 group than in the control group. Immunohistological analysis revealed that the numbers of 8-OHdG- and acrolein-positive cardiomyocytes and the degrees of myocardial and perivascular fibrosis were ameliorated by AST-120 administration. The myocardial fibrosis score was significantly associated with the 8-OHdG- (r = 0.848, P < 0.001) and acrolein-positive (r = 0.812, P < 0.001) cell scores. The perivascular fibrosis score was also significantly associated with the 8-OHdG- (r = 0.906, P < 0.0001) and acrolein-positive (r = 0.789, P < 0.001) cell scores.Conclusions. Oxidative stress is suggested to play a key role in the development of cardiac hypertrophy and fibrosis in CKD. AST-120 may suppress oxidative stress and reduce cardiac damage in CKD.