# Role of Sulfide Quinone Oxidoreductase and Supersulfides in Hepatic Ischemia–Reperfusion Injury in Mice

## TL;DR

This study shows that SQOR and supersulfides protect the liver from injury during ischemia and reperfusion, suggesting sodium trisulfide could be a treatment.

## Contribution

The study reveals a novel protective role of SQOR and supersulfides in hepatic IRI and identifies sodium trisulfide as a potential therapeutic.

## Key findings

- SQOR protects the liver by supporting mitochondrial electron transport and maintaining NAD redox balance.
- Sodium trisulfide reduces oxidative stress and preserves sulfide oxidation enzymes during IRI.
- SQOR and supersulfides exhibit antioxidative and redox-regulating functions in liver injury.

## Abstract

Hepatic ischemia–reperfusion injury (IRI) is a critical clinical condition associated with liver transplantation and acute liver injury. This study investigated the role of sulfide quinone oxidoreductase (SQOR) and its downstream product, supersulfides, in hepatic IRI. C57BL/6NJ mice were subjected to 45 min of partial hepatic ischemia, followed by reperfusion lasting 4 h. Control of shRNA mediated knockdown of SQOR expressing adeno-associated viral vectors were administered 3 weeks prior to liver ischemia. In the shRNA-mediated knockdown of SQOR group, the hydro-trisulfide donor sodium trisulfide was administered daily for 1 week prior to the induction of liver ischemia. SQOR played a crucial protective role during hepatic IRI by facilitating electron transport to the mitochondrial respiratory chain and maintaining the oxidized and reduced nicotinamide adenine dinucleotide ratio. Administration of sodium trisulfide, exhibited protective effects against hepatic IRI. Sodium trisulfide restored the oxidized and reduced nicotinamide adenine dinucleotide ratio, reduced oxidative stress, and preserved the expression of key enzymes involved in the sulfide oxidation pathway. SQOR and supersulfides contribute to hepatic protection against IRI, likely through their potent antioxidative and redox-regulating functions, and highlight sodium trisulfide as a potential therapeutic agent.