Premium
Anti‐oxidative effect of AST‐120 on kidney injury after myocardial infarction
Author(s) -
Fujii Hideki,
Yonekura Yuriko,
Yamashita Yusuke,
Kono Keiji,
Nakai Kentaro,
Goto Shunsuke,
Sugano Mikio,
Goto Sumie,
Fujieda Ayako,
Ito Yoshiharu,
Nishi Shinichi
Publication year - 2016
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13417
Subject(s) - medicine , kidney disease , oxidative stress , myocardial infarction , kidney , acute kidney injury , endocrinology , urine , gastroenterology
Background and Purpose Chronic kidney disease (CKD) is a crucial risk factor for cardiovascular disease (CVD), and combined CKD and CVD further increases morbidity and mortality. Here, we investigated effects of AST‐120 on oxidative stress and kidney injury using a model of myocardial infarction (MI) in rats. Experimental Approach At 10 weeks, male spontaneously hypertensive rats (SHR) were divided into three groups: SHR ( n = 6), MI ( n = 8) and MI + AST‐120 ( n = 8). AST‐120 administration was started at 11 weeks after MI. At 18 weeks, the rats were killed, and blood and urine, mRNA expression and renal histological analyses were performed. Echocardiography was performed before and after MI. Key Results At 18 weeks, the BP was significantly lower in the MI and MI+AST‐120 groups than in the SHR group. Elevated levels of indoxyl sulfate (IS), one of the uremic toxins, in serum and urine were reduced by AST‐120 treatment, compared with the MI group. Markers of oxidative stress in urine and serum biomarkers of kidney injury were decreased in the MI+AST‐120 group compared with the other two groups. Renal expression of mRNAs for kidney injury related‐markers were decreased in the MI+AST‐120 group, compared with the MI group. In vitro data also supported the influence of IS on kidney injury. Immunohistological analysis showed that intrarenal oxidative stress was reduced by AST‐120 administration. Conclusions and Implications Serum IS was increased after MI and treatment with AST‐120 may have protective effects on kidney injury after MI by suppressing oxidative stress.