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Updated: Aug 14, 2026
Isogenic Kidney Glomerulus Chip Engineered from Human Induced Pluripotent Stem Cells
Published on: November 4, 2022
Statin induces epithelial cell death and tissue barrier damage in renal tubule on chip
Shiquan Wang1, Yaqi Liu2, Daqing Wang2
1Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Abstract:
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.
Insights
Statins like lovastatin can harm kidney cells, causing oxidative stress and damage. This study developed a kidney chip to model and investigate these statin-induced renal side effects in vitro.
Area of Science:
- Nephrology
- Toxicology
- Biotechnology
Background:
- Statins are widely prescribed for lipid reduction but may cause cytotoxicity.
- Clinical observations suggest statin-induced kidney damage, but in vivo evidence is lacking.
- A need exists for reliable in vitro models to study drug nephrotoxicity.
Purpose of the Study:
- To develop and validate a human renal tubule chip for assessing statin-induced cytotoxicity.
- To investigate the mechanisms underlying lovastatin-induced nephrotoxicity.
- To establish a platform for evaluating drug-related renal side effects.
Main Methods:
- Co-culture of human proximal tubular epithelial cells and umbilical vein endothelial cells under fluidic flow.
- Application of lovastatin (25 μM) for 48 hours.
- Assessment of cell viability (CCK-8), membrane integrity (LDH leakage), barrier function, and reactive oxygen species (ROS) production.
Main Results:
- Lovastatin significantly reduced cell viability, increased LDH leakage, and impaired barrier integrity.
- Elevated ROS levels were observed in lovastatin-treated cells.
- Contrary to expectations, N-acetylcysteine or GSH exacerbated injury, while sodium pyruvate mitigated damage and ROS levels.
Conclusions:
- Lovastatin induces nephrotoxicity through oxidative stress pathways, potentially involving glutathione (GSH).
- The human renal tubule chip is a viable model for studying drug cytotoxicity and statin-related renal effects.
- This platform facilitates in vitro assessment of drug safety and mechanistic investigations.
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