Sodium thiosulfate refuels the hepatic antioxidant pool reducing ischemia-reperfusion-induced liver injury

GND
1114741418
ORCID
0000-0002-6089-6764
Affiliation
Jena University Hospital, Department of Anesthesiology and Intensive Care Medicine, Jena
Press, Adrian T.;
GND
1114743429
Affiliation
Jena University Hospital, Department of Anesthesiology and Intensive Care Medicine, Jena
Ungelenk, Luisa;
GND
1058276409
Affiliation
Applied Systems Biology, HKI-Center for Systems Biology of Infection, Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Kn¨oll-Institute (HKI), Jena,
Medyukhina, Anna;
Affiliation
Department of Biological Sciences, University of North Carolina, Charlotte, NC, USA
Pennington, Samantha A.;
GND
12341461X
Affiliation
Jena University Hospital, Electron Microscopy Center, Jena
Nietzsche, Sandor;
GND
1164188895
Affiliation
Jena University Hospital, Department of General, Visceral and Vascular Surgery, Experimental Transplantation Surgery, Jena
Kan, Chunyi;
GND
112354025
Affiliation
Jena University Hospital, Department of General, Visceral and Vascular Surgery, Experimental Transplantation Surgery, Jena
Lupp, Amelie;
GND
114498405X
Affiliation
cJena University Hospital, Department of General, Visceral and Vascular Surgery, Experimental Transplantation Surgery, Jena
Dahmen, Uta;
ORCID
0000-0003-3825-3620
Affiliation
Department of Biology, York University, Toronto, Canada
Wang, Rui;
GND
172370469
Affiliation
Jena University Hospital, Department of General, Visceral and Vascular Surgery, Experimental Transplantation Surgery, Jena
Settmacher, Utz;
GND
1178449637
Affiliation
Jena University Hospital, Department of Anesthesiology and Intensive Care Medicine, Jena
Wetzker, Reinhard;
GND
1146344732
Affiliation
Applied Systems Biology, HKI-Center for Systems Biology of Infection, Leibniz-Institute for Natural Product Research and Infection Biology, Hans-Kn¨oll-Institute (HKI), Jena
Figge, Marc Thilo;
Affiliation
Department of Biological Sciences, University of North Carolina, Charlotte, NC, USA
Clemens, Mark G.;
GND
137650922
ORCID
0000-0002-1521-3514
Affiliation
Jena University Hospital, Department of Anesthesiology and Intensive Care Medicine, Jena
Bauer, Michael

Ischemia-reperfusion injury is a critical liver condition during hepatic transplantation, trauma, or shock. An ischemic deprivation of antioxidants and energy characterizes liver injury in such cases. In the face of increased reactive oxygen production, hepatocytes are vulnerable to the reperfusion driving ROS generation and multiple cell-death mechanisms. In this study, we investigate the importance of hydrogen sulfide as part of the liver's antioxidant pool and the therapeutic potency of the hydrogen sulfide donors sodium sulfide (Na2S, fast releasing) and sodium thiosulfate (STS, Na2S2O3, slow releasing). The mitoprotection and toxicity of STS and Na2S were investigated on isolated mitochondria and a liver perfusion oxidative stress model by adding text-butyl hydroperoxide and hydrogen sulfide donors. The respiratory capacity of mitochondria, hepatocellular released LDH, glutathione, and lipid-peroxide levels were quantified. In addition, wild-type and cystathionine-γ-lyase knockout mice were subjected to warm selective ischemia-reperfusion injury by clamping the main inflow for 1 h followed by reperfusion of 1 or 24 h. A subset of animals was treated with STS shortly before reperfusion. Glutathione, plasma ALT, and lipid-peroxide levels were investigated alongside mitochondrial changes in structure (electron microscopy) and function (intravital microscopy). Liver tissue necrosis quantified 24 h after reperfusion indicates the net effects of the treatment on the organ. STS refuels and protects the endogenous antioxidant pool during liver ischemia-reperfusion injury. In addition, STS-mediated ROS scavenging significantly reduced lipid peroxidation and mitochondrial damage, resulting in better molecular and histopathological preservation of the liver tissue architecture. STS prevents tissue damage in liver ischemia-reperfusion injury by increasing the liver's antioxidant pool, thereby protecting mitochondrial integrity.

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