Effect of hydrogen sulphide on inflammatory factors of the mitochondria after limb ischaemia‐reperfusion injury in rats

Abstract

The goal of this study was to evaluate the effect of hydrogen sulphide on inflammatory factors and the energy metabolism of mitochondria after limb reperfusion injury in rats. Sixty Wistar rats were divided into three groups: the sham operated group, the control group (the ischaemia‐reperfusion injury [IRI] + normal saline group), and the experimental group (the IRI + H2S group). An experimental rat model of limb IRI was established. Skeletal muscle samples were collected to observe the content of necrotic products (including myoglobin (MB), lysophosphatidylcholine (LPC), and lipid peroxidation (LPO)); blood samples were collected to observe changes in the contents of interleukin‐1 (IL‐1), Interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α); and the mitochondria of skeletal muscle cells were extracted for mitochondrial transmembrane potential measurement and adenosine triphosphate (ATP) content determination. The results underwent further statistical analysis. The contents of MB, LPC, and LPO in the limb skeletal muscle, liver, lung, and kidney tissues of rats in the control group were significantly increased (P < 0.05) after IRI, which was markedly attenuated by treatment with hydrogen sulphide (P < 0.05). Ischaemia/reperfusion of the lower extremities in rats triggered a significant increase in serum levels of IL‐1, IL‐6, and TNF‐α, which was significantly inhibited by treatment with H2S during ischaemia/reperfusion. In addition, the inhibitory effect tended to be time‐dependent. After limb ischaemia/reperfusion, the mitochondrial transmembrane potential of skeletal muscle cells in the control group decreased significantly (P < 0.05), while the potential energy of the mitochondrial membrane in the experimental group was significantly higher than that in the control group (P < 0.05). The content of ATP in mitochondria of skeletal muscle cells of ischaemia‐reperfusion rats in the control group was significantly lower than that in the sham operated group (P < 0.05), while the content of ATP of mitochondria in the experimental group after H2S treatment was significantly higher than the control group (P < 0.05). Hydrogen sulphide can alleviate the injury of skeletal muscle and distal organs after limb ischaemia‐reperfusion and reduce local inflammatory reaction, which is essential in alleviating mitochondrial transmembrane potential and energy metabolism disorder during reperfusion injury. The purpose of the study is to summarise the available information and provide theoretical support for the application of hydrogen sulphide in the treatment of limb IRI in skeletal muscle and distal organs.

The double-edged role of hydrogen sulfide in the pathomechanism of multiple liver diseases

“…There have been significant advances in animal studies focusing on the molecular pathways of H 2 S in I/R injury (Lu et al, 2018;Fu et al, 2019;Ibrahim et al, 2021). Recent studies have found that fatty livers are more susceptible to ischemia/ reperfusion (I/R) damage during liver surgery and transplantation (Varela et al, 2011).…”

“…Therefore, retaining an appropriate level of H 2 S in ischemia-reperfusion (I/R) is imperative in protecting the liver from injury. NaHS protects the liver against I/R and, as a donor of H 2 S, is protective against hepatic I/R injury, a process associated with the activation of antioxidant enzymes and decreased expression of hepatic tumor necrosis factor-α (TNF-α), MDA, and caspase-3 (Fu et al, 2019).…”

“…Cold ischemia-reperfusion injury (IRI) poses a significant threat to the success of solid organ transplantation (SOT) (Muller et al, 2022). A study discussing the molecular mechanisms underlying the role of H 2 S donor molecules in liver transplantation showed that H 2 S could significantly attenuate IRI during liver transplantation by inhibiting a range of interrelated cells and molecules, including those related to microcirculatory dysfunction and microvascular dysfunction, mitochondrial damage, inflammatory responses, cellular injury, cell death, and other destructive molecular pathways, while promoting the protective pathways (Balaban et al, 2011;Fu et al, 2019). These promising findings will be the basis of the clinical application of H 2 S in the future (Dugbartey et al, 2021).…”