TNF-α-downregulated SIRT1 regulates mitochondrial-autophagy and apoptosis in renal vascular endothelial cells involved in trichloroethylene-induced immune kidney injury.

Occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) represents a critical clinical issue, with patients frequently experiencing multi-organ damage, including renal impairment. The underlying mechanisms, however, remain elusive. This study investigated how trichloroethylene (TCE) sensitization-induced tumor necrosis factor alpha (TNF-α) deposition in renal vascular endothelial cells affects apoptosis and its underlying mechanisms. A TCE-sensitized mouse model was established using 6-8-week-old female BALB/c mice. The TNF-α inhibitor R7050 (12 mg/kg) and the sirtuin 1 (SIRT1) activator SRT1720 (5 mg/kg) were employed for therapeutic intervention. Significant kidney damage and mitochondrial impairment were observed in TCE-sensitized positive mice. While treatment with R7050 reduced kidney damage and cell apoptosis, SRT 1720 restored mitochondrial function and increased mitochondrial autophagy in renal endothelial cells. In vitro experiments with recombinant human TNF-α (100 ng/mL for 48 h) on human umbilical vein endothelial cells (HUVEC) showed that TNF-α suppresses SIRT1 expression. This elevation of TNF-α also inhibited the SIRT1-activated PINK1-Parkin mitochondrial autophagy pathway, causing mitochondrial dysfunction and leading to apoptosis in renal vascular cells.