TY - JOUR
T1 - Kidney toxicology of a novel compound Lithium Bis(trifluoromethanesulfonyl)imide (LiTFSI, ie. HQ-115) used in energy applications
T2 - An epigenetic perspective
AU - Sands, Mia
AU - Zhang, Xing
AU - Irudayaraj, Joseph
N1 - This work was funded by start-up grant to JI at the University of Illinois at Urbana-Champaign and grant from the Internal Research Board. We acknowledge funding from Research Training Program in Toxicology and Environmental Health 5T32ES007326\u201309 of the University of Illinois at Urbana-Champaign.
The authors acknowledge Dr. Arnon Gal for assistance with histologic examination, the Roy J. Carver Biotechnology Center at the University of Illinois at Urbana-Champaign for assistance in sequencing support, the Carver Metabolomics core for assistance with LC-MS, and the Veterinary Diagnostic Laboratory for aiding in biochemical profiles. Biological assessments were performed at the Tumor Engineering and Phenotyping Facility at the Cancer Center at Illinois. All animal-related procedures were carried out at the Beckman Institute.
PY - 2024/12/10
Y1 - 2024/12/10
N2 - 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.
AB - 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.
KW - DNA methylation
KW - Lithium Bis(trifluoromethanesulfonyl)imide (LiTFSI, ie. HQ-115)
KW - Nephrotoxicity
KW - PFAS
KW - PFOA
KW - Uric acid metabolism
UR - https://www.scopus.com/pages/publications/85207051629
UR - https://www.scopus.com/pages/publications/85207051629#tab=citedBy
U2 - 10.1016/j.scitotenv.2024.177019
DO - 10.1016/j.scitotenv.2024.177019
M3 - Article
C2 - 39447891
AN - SCOPUS:85207051629
SN - 0048-9697
VL - 955
JO - Science of the Total Environment
JF - Science of the Total Environment
M1 - 177019
ER -