Atorvastatin protects against contrast-induced nephropathy via anti-apoptosis by the upregulation of Hsp27 in vivo and in vitro

Abstract

Contrast-induced nephropathy (CIN) is an iatrogenic acute renal failure occurring following the intravascular injection of iodinated radiographic contrast medium. However, the regulatory mechanisms for CIN remain to be fully elucidated. The present study aimed to investigate whether atorvastatin protects against CIN via anti-apoptotic effects by the upregulation of Hsp27 in vivo and in vitro. To determine whether atorvastatin attenuated CIN, the inflammatory response and apoptosis in vivo and in vitro, a rat model of iopamidol-induced CIN was used, and human embryonic proximal tubule (HK2) cell damage was assessed. The rats were assigned into four groups (n=10 per group), as follows: Control rats; rats+atorvastatin; rats + iopamidol; rats+iopamidol+atorvastatin. In vitro, the HK2 cells were treated with iopamidol in the presence or absence of atorvastatin, heat shock protein (Hsp)27 small interfering (si)RNA or pcDNA3.1-Hsp27. The renal tissues were examined histopathologically and collected for western blot analysis. The results showed that atorvastatin ameliorated the apoptosis and deterioration of renal function (P<0.05). Furthermore, atorvastatin reduced the iopamidol-induced activity of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax)/caspase-3 and increased the expression of Bcl-2 in vivo and in vitro. Notably, following treatment with Hsp27 siRNA or pcDNA3.1-Hsp27, it was found that iopamidol enhanced or weakened the upregulation of Bax/caspase-3 and downregulation of Bcl-2 in the HK2 cells, respectively. The results of the present study suggested that atorvastatin protected against contrast-induced renal tubular cell apoptosis through the upregulation of Hsp27 in vivo and in vitro.

Oxidative stress caused by activation of NADPH oxidase 4 promotes contrast-induced acute kidney injury

“…Several regimens, such as N-acetylcysteine (NAC; a reactive oxygen scavenger), ascorbic acid, tocopherol, and atorvastatin, have been evaluated for reducing reactive oxygen species (ROS) levels to prevent CIAKI [ 24 – 27 ]. However, the preventive effects have been equivocal in many clinical studies [ 28 – 31 ].…”

The molecular mechanism of contrast-induced nephropathy (CIN) and its link to in vitro studies on iodinated contrast media (CM)

“…Increasing Bax, caspase-3 protein levels and decreasing Bcl-2, HSP70 protein levels by western. [ 63 ] LLC-PK1 (Pig renal tubular epithelial cells) Iodixanol (Visipaque) 4.7-75 mgI/ ml 2h , 24h 1. Decreasing cell proliferation by MTT assay.…”

Protective Effects of Simvastatin on Endotoxin-Induced Acute Kidney Injury through Activation of Tubular Epithelial Cells’ Survival and Hindering Cytochrome C-Mediated Apoptosis

“…By inhibition of hydroxy-3-methylglutaryl-CoA (HMG-CoA), reductase statins block the mevalonate pathway and activation of intermediate products involved in cell signaling pathways, such as apoptosis or cell survival. One previous study showed that atorvastatin ameliorated contrast-induced nephropathy and reduced the extent of renal tubular cell apoptosis that is associated with the decreased expression of proapoptotic Bax/caspase-3 and increased Bcl-2 [ 17 ]. Another study that demonstrated the renoprotective effects of pitavastatin on cisplatin-induced AKI pointed to suppression of the mitogen-activated protein kinase (MAPK)/NF-kB/inflammation axis and intrinsic apoptotic pathway [ 18 ].…”