Format

Send to

Choose Destination
J Pharmacol Sci. 2016 May;131(1):18-27. doi: 10.1016/j.jphs.2016.03.006. Epub 2016 Mar 18.

Atorvastatin attenuates contrast-induced nephropathy by modulating inflammatory responses through the regulation of JNK/p38/Hsp27 expression.

Author information

1
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Disease, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
2
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Disease, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. Electronic address: chenjiyan741@163.com.
3
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Disease, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China. Electronic address: zhouyingling852@163.com.

Abstract

This study aimed to investigate whether atorvastatin reduce the contrast-induced nephropathy inflammatory response and apoptosis of renal tubular epithelial cells and the relationship with MAPK signaling pathway. We utilized the iopamidol-induced contrast-induced nephropathy (CIN) rat model which was induced by a single dose of iopamidol (2.9 g iodine/kg) and a cell model in which human embryonic proximal tubular (HK2) cells were treated with iopamidol. The rats were divided into five groups: (1) control rats (CR); (2) atorvastatin (CA); (3) iopamidol (CM); (4) iopamidol and atorvastatin (20 mg/kg d) (CMA2); (5) iopamidol and atorvastatin (40 mg/kg d) (CMA4). On days 1, 2 and 6 after iopamidol injection, the urea nitrogen and cystatin C increased in CM compared with CR but decreased in CMA compared with CM. Inflammatory parameters and the percentage of apoptotic cells were increased in CM compared with CR and CA, but they were decreased in CMA compared with CM. We also found that atorvastatin ameliorated the renal tubular necrosis, apoptosis, and the deterioration of renal function in a dose dependent manner (P < 0.05). Furthermore, in vivo, both of SP600125 (JNK inhibitor) and SB203580 (p38 inhibitor) could decrease the expression of Bax and caspase-3, but increase Bcl-2 levels in HK2 cells treated with iopamidol. Our study demonstrates that high-dosage atorvastatin treatment attenuates both the inflammatory processes and apoptosis in contrast-induced acute kidney injury, and that the JNK/p38 MAPK pathway participates in the contrast-induced apoptosis of renal tubular cells. Finally, atorvastatin reduces CIN by suppression of apoptosis, which may be through inhibition of JNK/p38 MAPK pathways.

KEYWORDS:

Apoptosis; Atorvastatin; Contrast-induced nephropathy (CIN); Inflammatory processes; JNK/p38 MAPK pathway

PMID:
27156929
DOI:
10.1016/j.jphs.2016.03.006
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center