Sodium selenite attenuates sepsis-induced cardiac inflammation and oxidative injury by regulating TXN2/TXNIP/NLRP3 signaling and ferroptosis.

Septic cardiomyopathy is cardiac dysfunction caused by sepsis and is a common consequence of sepsis. Clinical studies have found patients with sepsis syndrome commonly have low serum selenium (Se) levels, and Se supplementation at doses higher than the daily requirement may reduce mortality; however, the underlying mechanism remains unclear. We found that downregulation of thioredoxin-2 (TXN2)-induced mitochondrial reactive oxygen species (mtROS), which increased inflammatory and oxidative injury in cardiomyocytes, might be a major contributor to septic cardiomyopathy. Mitoquinone mesylate (MitoQ), an antioxidant specifically targeted to mitochondria, increased TXN2 expression and decreased mtROS, thioredoxin-interacting protein (TXNIP, a negative regulator of TXN), nucleotide-binding oligomerization domain (NOD)-like receptor protein-3 (NLRP3) inflammasome activation, and ferroptosis. The results suggest that the TXN2-ferroptosis-NLRP3 pathway may represent a therapeutic target for sepsis-induced cardiac injury. In addition, we found that Se supplementation improved cardiac function and relieved mtROS accumulation and ferroptosis in sepsis-associated cardiac injury by regulating TXN2 and TXNIP/NLRP3 expression.