Atorvastatin inhibits renal inflammatory response induced by calcium oxalate crystals via inhibiting the activation of TLR4/NF ‐κB and NLRP3 inflammasome

This study aimed to investigate the renal protective effect of atorvastatin (ATV) on the kidney inflammation induced by calcium oxalate (CaOx) crystals. A cell model of cell ‐crystal interactions and a rat model of CaOx kidney stone were established. The expressions of TLR4, NF‐κB, NLRP3, and cleaved caspase‐1 in cells and rat kidney tissues were detected using Western blot, immunohistochemical, and/or immunofluorescence. The concentrations of malondialdehyde (MD A), superoxide dismutase (SOD), reactive oxygen species (ROS) in cells, and lactic acid dehydrogenase (LDH) in the culture medium were measured. The secreted levels of interleukin (IL)‐1β, IL‐18, IL‐6, and tumor necrosis factor‐α (TNF‐α) were examined by ELISA. The serum levels of creat inine (CRE) and blood urea nitrogen (BUN) were measured. von Kossa staining was used for the evaluation of renal lens deposition. The CaOx model group showed significantly decreased SOD level; increased concentrations of MDA; ROS and LDH; elevated expressions of TLR4, NF‐κB, NLRP3, and cleaved ca spase‐1; and the elevated release of IL‐1β, IL‐18, IL‐6, and TNF‐ α as compared to the control group. The treatment with ATV significantly inhibited the formation of CaOx kidney stone by increasing the level of SOD; downregulating MDA, ROS, and LDH; inhibiting the expressions of TLR4, NF ‐κB, NLRP3 and cleaved caspase‐1; and blocking the secretion of inflammatory cytokines. In addition, the serum levels...
Source: IUBMB Life - Category: Research Authors: Tags: RESEARCH COMMUNICATION Source Type: research