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

Abstract

Abstract. 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.

Mitophagy Plays a Protective Role in Iodinated Contrast-Induced Acute Renal Tubular Epithelial Cells Injury

“…Taken together, based on previous study [19] and our experimental results, both iohexol and iodixanol caused mitochondrial damage, autophagy, and mitophagy. However, iohexol induced more markedly decrease in cell viability than iodixanol.…”

“…Based on previous study [19], we select the concentration of 200 mg iodine/ml of iohexol or iodixanol and treatment duration of 6 h for further study on mitochondrial damage and ROS generation. The exposure of iohexol or iodixanol led to a significant increase in the signals of fluorescent MitoSOX, suggesting a reinforcement in ROS production (Fig.…”

“…HK-2 cells were incubated in the FBS-free DMEM/F12 medium for 12 h. The cytotoxicity of HK-2 cells were evaluated after exposure to different concentrations of iohexol or iodixanol at the time points of 0 h, 2 h, 4 h, 6 h, 8 h. An injured cell mitophagy model was chosen based on our previous study [19]. Rap (100 nM) or 3-MA (10 mM) were used to enhance or inhibit the formation of autophagosomes and mitophagy respectively.…”

An evaluation of the antioxidant properties of iodinated radiographic contrast media: An in vitro study

“…Iodinated radiographic contrast media also increased cytotoxicity in human proximal renal tubular epithelial cells [ 32 , 33 ]. Other authors showed that iodinated radiographic contrast media caused severe and prolonged oxidative stress in hemodialysis patients.…”

Autophagy is activated to protect renal tubular epithelial cells against iodinated contrast media-induced cytotoxicity

“…Cell treatment. HK-2 cells were incubated in FBS-free DMEM/F12 for 12 h. The establishment of a damaged cells model was performed as previously reported (11). 3-MA (10 mM) was used to inhibit the formation of autophagosomes.…”