Statin induces epithelial cell death and tissue barrier damage in renal tubule on chip

Although statins are widely used to reduce lipid levels, they can lead to cytotoxicity in various cell types when given at certain dosages. The effects of statins on kidney epithelial cells are speculated based on clinical phenomena but remain unverified in animal models. Here, we described a human renal tubule chip that allows the evaluation of statin-induced cytotoxicity. The renal chip was constructed by co-culturing human proximal tubular epithelial cells and umbilical vein endothelial cells under fluidic flow. In this model, the effects of lovastatin (25 μM) on the cells over 48 h were tested using the CCK-8, Lactate Dehydrogenase leakage, permeability tests and ROS production assays. Our findings revealed that lovastatin reduced cell viability, increased Lactate Dehydrogenase leakage, and impaired barrier integrity while elevating ROS levels. Different from what we expected, lovastatin-treated epithelial cells exhibited exacerbated tubular injury and further increased ROS production following the addition of N-acetylcysteine or GSH. In contrast, sodium pyruvate attenuated lovastatin-induced ROS levels and barrier damage in the chip. These findings demonstrate that lovastatin induces oxidative stress via GSH, with ROS-mediated pathways driving tubular injury. This study establishes a platform for the in vitro assessment of drug cytotoxicity and the investigation of statin-related renal side effects.

Cytotoxicity; Drug evaluation; Lovastatin; Oxidative stress; Renal tubule on chip.