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Cutaneous arsenical exposure induces distinct metabolic transcriptional alterations of kidney cells

ABSTRACT: Arsenicals are deadly chemical warfare agents which primarily cause death through systemic capillary fluid leakage and hypovolemic shock. Arsenicals are also known to cause acute kidney injury, a condition that contributes to arsenical-associated death due to the necessity of the kidney in maintaining whole-body fluid homeostasis. Because of the global health risk that arsenicals pose, a nuanced understanding of how arsenical exposure can lead to kidney injury is needed. Our study utilized a non-targeted transcriptional approach to evaluate the effects of cutaneous exposure to phenylarsine oxide, a common arsenical, in a murine model. Here, we demonstrate an upregulation of metabolic pathways such as fatty acid oxidation and PPAR- signaling within proximal tubule epithelial cells and endothelial cells in the kidney. We also reveal highly upregulated single genes related to metabolism and metabolic switching within these same cell types which may serve as future therapeutic targets. The ability of arsenicals to inhibit enzymes such as pyruvate dehydrogenase have been previously described in vitro. This along with our own data lead us to conclude that arsenical-induced acute kidney injury may be due to a metabolic impairment in proximal tubule and endothelial cells, and that appropriately ameliorating these metabolic effects may lead to the development of life-saving therapies.

ORGANISM(S): Mus musculus

PROVIDER: GSE233859 | GEO | 2023/09/07

REPOSITORIES: GEO

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