Conclusion
Results suggest that PCT cell exposure to SAD SiNPs could promote glycolytic and fibrotic shifts consistent with CKDu pathology via oxidative stress-mediated disruption of redox signaling pathways.
Methods
In order to characterize the impact of sugarcane ash derived (SAD) SiNPs on human kidney proximal convoluted tubule (PCT) cells and identify potential mechanisms of toxicity, HK-2 cells were exposed to treatments of either pristine, manufactured, 200 nm SiNPs or SAD SiNPs and changes to cellular energy metabolism and redox state were determined. To determine how the cellular redox environment may influence PCT cell function and toxicity, the redox proteome was examined using cysteine-targeted click chemistry proteomics.
Results
Pristine, 200 nm SiNPs induced minimal changes to energy metabolism and proteomic profiles in vitro while treatment with SAD SiNPs resulted in mitochondrial membrane hyperpolarization, inhibited mitochondrial respiration, increased reactive oxygen species generation, and redox proteomic trends suggesting activation of aryl hydrocarbon receptor (AHR) and other signaling pathways with known roles in mitochondrial inhibition and CKD progression.