Sodium thiosulfate attenuates liver injury in a rat model of sepsis by modulating ferroptosis and oxidative stress.

Sepsis is a dysregulated immune response to infection that can present with a pro-inflammatory endotype in which the ischemia/reperfusion injury leads to excessive production of reactive oxygen species (ROS), inflammatory mediators and the activation of cell death mechanisms. Sodium thiosulfate (STS) is a hydrogen sulfide producing agent that could reduce ischemia/reperfusion injuries induced ROS, inflammation and cell death. We used the peritoneal contamination and infection model in adult rats to induce sepsis. Animals from the treatment groups received either Trolox, an antioxidant medication or STS in doses of 500mg/kg b.w. (STS500 group) or 1000mg/kg b.w. (STS1000 group). Additionally all rats received fluid resuscitation therapy, antibiotic therapy and analgesic treatment. After 48 h the rats were sacrificed and blood and liver samples collected for analysis. Both STS500 and STS1000 reduced overall the ROS production and improved antioxidant defence mechanisms. They also reduced inflammatory cytokines IL-6 and TNF-α levels. In liver samples STS reduced inflammatory alterations and ferroptosis but had little effect on pyroptosis. STS could be a potential treatment option is sepsis pro-inflammatory endotypes by improving the redox balance and inhibiting ferroptosis and inflammation.