An in vivo and in vitro model on the protective effect of cilnidipine on contrast‐induced nephropathy via regulation of apoptosis and CaMKⅡ/mPTP pathway

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Contrast‐induced nephropathy (CIN) is an acute kidney injury (AKI) observed after the administration of contrast media. Calcium channel blockers (CCBs) have been reported to exert a renal protective effect. This study aims to investigate the role of cilnidipine, a novel CCBs, on CIN by regulating the calcium/calmodulin‐dependent protein kinase Ⅱ(CaMKⅡ)/mitochondrial permeability transition pore (mPTP) pathway. Here, iohexol, a representative contrast media, was used to establish CIN model. KN‐93 (CaMKⅡ inhibitor) and atractyloside (mPTP opener) were administered in rats, and CaMKⅡ overexpression was used in Human proximal tubular epithelial cells. Markers of renal injury (serum creatinine, blood urea nitrogen, and urinary NAGL), hematoxylin‐eosin stain, oxidative stress (ROS, superoxide dismutase [SOD], and malondialdehyde [MDA] levels), cell death (MTT and terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labeling [TUNEL]), mitochondrial function (mPTP, mitochondrial membrane potential [MMP], and ATP) were assessed. Western blots were used to measure the expression levels of Bax/Bcl‐2, caspase‐3, CaMKⅡ/mPTP signaling pathways. Results showed that cilnidipine markedly improved kidney function, and alleviated tubular cell apoptosis, oxidative stress and mitochondrial damage induced by iohexol in vitro and in vivo. The underlying mechanism may be that cilnidipine relieved CaMKⅡ activation and mPTP opening induced by iohexol. All of these protective effects of cilnidipine were attenuated by CaMKⅡ overexpression and atractyloside (mPTP opener) pretreatment. Moreover, KN‐93 (CaMKⅡ inhibitor) treatment showed a similar renal protective effect with cilnidipine, while the protective effect of cilnidipine on kidney in CIN rats was not further suppressed by KN‐93 cotreatment. These in vitro and in vivo results point toward the fact that cilnidipine might be a novel therapeutic drug against contrast‐induced nephrotoxicity in a CaMKⅡ‐dependent manner.

Related collections

Most cited references 45

Record: found
Abstract: found
Article: found

Is Open Access

Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)

John A. Kellum, Norbert Lameire (2013)

Acute kidney injury (AKI) is a common and serious problem affecting millions and causing death and disability for many. In 2012, Kidney Disease: Improving Global Outcomes completed the first ever, international, multidisciplinary, clinical practice guideline for AKI. The guideline is based on evidence review and appraisal, and covers AKI definition, risk assessment, evaluation, prevention, and treatment. In this review we summarize key aspects of the guideline including definition and staging of AKI, as well as evaluation and nondialytic management. Contrast-induced AKI and management of renal replacement therapy will be addressed in a separate review. Treatment recommendations are based on systematic reviews of relevant trials. Appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendations Assessment, Development and Evaluation approach. Limitations of the evidence are discussed and a detailed rationale for each recommendation is provided.

0 comments Cited 562 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Hospital-acquired renal insufficiency.

Kevin Nash, Abdul Hafeez, Susan Hou (2002)

Despite myriad improvements in the care of hospitalized patients, a decline in renal function remains a common event. Renal function in 4,622 consecutive patients admitted to the medical and surgical services of an urban tertiary care hospital was followed up prospectively from the time of admission. Some degree of renal insufficiency developed in 7.2% of patients. Decreased renal perfusion, medications, surgery, and radiographic contrast media were the most common causes of hospital-acquired renal insufficiency (HARI). The overall mortality rate was 19.4% and was similar among patients for all causes of renal insufficiency, except sepsis. For patients with a greater than 3.0-mg/dL increase in serum creatinine level, the mortality rate was 37.8%. As shown by previous investigators, age and preexisting renal insufficiency were risk factors for HARI. Women and blacks had less hospital-acquired renal failure. The increasing acuity of hospital admissions has been accompanied by a greater incidence of acute renal insufficiency in patients admitted to hospitals. There is a trend toward better survival in patients with a severe deterioration in renal function. Copyright 2002 by the National Kidney Foundation, Inc.