Kidney toxicology of a novel compound Lithium Bis(trifluoromethanesulfonyl)imide (LiTFSI, ie. HQ-115) used in energy applications: An epigenetic perspective

Exposure to emerging energy-based environmental contaminants such as lithium bis(trifluoromethanesulfonyl)imide (LiTFSI, trade name HQ-115), poses a significant threat to human health, yet its impact on kidney function and epigenetic regulation remains poorly understood. Here, we investigated the effects of LiTFSI exposure on kidney-related biochemical indicators, renal injuries, and epigenetic alterations in male CD-1 mice under both 14-day and 30-day exposure durations. Our study revealed that LiTFSI exposure led to changes in kidney-related markers, notably affecting serum bicarbonate levels, while relative kidney weight remained unaffected. Histological analysis revealed tubule dilation, inflammation, and loss of kidney structure in LiTFSI-exposed mice, alongside dysregulated expression of genes associated with inflammation, renal function, and uric acid metabolism. Epigenetic analysis further identified widespread DNA methylation changes in the two exposure regimes. Functional analysis revealed that differentially methylated regions are implicated in cell apoptosis and cancer-related pathways and are enriched with development-related transcription factor binding motifs, suggesting a potential mechanism of action underlying exposure induced kidney damage. These findings underscore the intricate interplay between environmental exposures, epigenetic modulation, and kidney health, emphasizing the need for additional research to unravel precise mechanisms and develop targeted interventions to mitigate the adverse effects of LiTFSI and exposure of similar clean energy compounds on human health.