Atorvastatin alleviates iodinated contrast media-induced cytotoxicity in human proximal renal tubular epithelial cells

摘要

Contrast media (CM)-induced nephropathy (CIN) is a serious complication of intravascularly applied radiocontrast media. At present, no drugs have been approved for the prevention of CIN. The present study aimed to explore the effects and potential mechanisms of atorvastatin on iodinated CM-induced cytotoxicity in the human proximal renal tubular epithelial cells. The cytotoxic effect of iohexol (50, 100 and 200 mg I/ml) and the protective effect of atorvastatin pretreatment (1, 20 and 40 µM) were assessed. The cytotoxicity of iohexol was evaluated via the MTT cell viability and lactate dehydrogenase assays. The amount of apoptotic cells was determined by flow cytometry. Morphological changes in HK-2 cells were observed via transmission electron microscopy. The mRNA expression of NOX4 and p22phox was measured through reverse transcription-quantitative polymerase chain reaction analysis. The cytotoxicity was induced by iohexol in HK-2 cells. Atorvastatin was identified to significantly alleviate the suppression of cell viability induced by iohexol. Notably, 40 µM atorvastatin also significantly reduced the mRNA expression of intracellular NOX4 and p22phox, and the percentage of apoptotic cells. Furthermore, morphological changes characteristic of injured cells were alleviated by atorvastatin pretreatment. These results suggest that atorvastatin exhibits a protective effect on HK-2 cells against iohexol-induced cytotoxicity through the downregulation of NOX4 and p22phox. Thus, atorvastatin is a potential therapeutic agent for the prevention of CIN and required further study.