Atorvastatin ameliorates contrast medium-induced renal tubular cell apoptosis in diabetic rats via suppression of Rho-kinase pathway.
Contrast medium-induced acute kidney injury (CI-AKI) remains a leading cause of iatrogenic, drug-induced acute renal failure. This study aimed to investigate the protective effects of atorvastatin against renal tubular cell apoptosis in diabetic rats and the related mechanisms. CI-AKI was induced by intravenous administration of iopromide (12ml/kg) in streptozotocin-induced diabetic rats. Atorvastatin (ATO) was administered intragastrically at the dose of 5, 10 and 30mg/kg/d in different groups, respectively, for 5 days before iopromide injection. Renal function parameters, kidney histology, renal tubular cell apoptosis, the expression of apoptosis regulatory proteins, caspase-3 and Rho-associated protein kinase 1 (ROCK-1), and the phosphorylation of myosin phosphatase target subunit -1 (MYPT-1), were determined. Atorvastatin was shown to notably ameliorate contrast medium induced medullary damage, restore renal function, and suppress renal tubular apoptosis. Meanwhile, atorvastatin up-regulated the expression of Bcl-2, down-regulated the expression of Bax, caspase-3 and ROCK-1, restored the ratio of Bcl-2/Bax, and suppressed the phosphorylation of MYPT-1 in a dose-dependent manner. Thus, atorvastatin pretreatment could dose-dependently ameliorate the development of CI-AKI, which was partly attributed to its suppression of renal tubular cell apoptosis by inhibiting the Rho/ROCK pathway.
Department of Cardiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Rd, Fuzhou 350005, China. Electronic address: sujinzi1@yahoo.com.cn.
Jinzi
J
Su
First Clinical College, Fujian Medical University, 20 Chazhong Rd, Fuzhou 350005, China; Department of Intensive Care Unit, Yichang Central Hospital, 183 Yiling Rd, Yichang 443003, China.
Wenbo
W
Zou
Department of Cardiology, First Affiliated Hospital of Fujian Medical University, 20 Chazhong Rd, Fuzhou 350005, China.
Wenqin
W
Cai
First Clinical College, Fujian Medical University, 20 Chazhong Rd, Fuzhou 350005, China.
Xiuping
X
Chen
First Clinical College, Fujian Medical University, 20 Chazhong Rd, Fuzhou 350005, China.
Fangbing
F
Wang
First Clinical College, Fujian Medical University, 20 Chazhong Rd, Fuzhou 350005, China.
Shuizhu
S
Li
Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan 430030, China.
Wenwen
W
Ma
Department of Internal Medicine, UCSF-Fresno Center for Medical Education and Research, 155N. Fresno Street, Fresno, CA 93701, USA.
Yangming
Y
Cao
D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin; D053148:Caspase 3 / Q000378:metabolism; D003287:Contrast Media; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D007472:Iohexol / Q000031:analogs & derivatives; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D054645:Protein Phosphatase 1 / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
C494828:Bax protein, rat; D003287:Contrast Media; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; D051028:bcl-2-Associated X Protein; D007472:Iohexol; C038192:iopromide; D000069059:Atorvastatin; C578418:ROCK1 protein, rat; D054460:rho-Associated Kinases; C499850:Ppp1r12a protein, rat; D054645:Protein Phosphatase 1; D053148:Caspase 3
Apoptosis; Atorvastatin; Contrast-induced acute kidney injury; Diabetic rat; ROCK-1