Beneficial effects of gaseous hydrogen sulfide in hepatic ischemia/reperfusion injury.
Hydrogen sulfide (H2 S) can induce a reversible hypometabolic state, which could protect against hypoxia. In this study we investigated whether H2 S could protect livers from ischemia/reperfusion injury (IRI). Male C57BL/6 mice were subjected to partial hepatic IRI for 60 min. Animals received 0 (IRI) or 100 ppm H2 S (IRI + H2 S) from 30 min prior to ischemia until 5 min before reperfusion. Core body temperature was maintained at 37° C. Animals were sacrificed after 1, 6 or 24 h. Hepatic ischemia caused extensive hepatic necrosis in the IRI animals which coincided with an increase in ALT and AST serum levels. Animals treated with H2 S showed attenuated serum ALT and AST levels and reduced necrotic lesions after 24 h. IRI animals had increased Bcl-2 mRNA expression and increased active Caspase 3 protein, which were both significantly lower in H2 S treated animals. Increased TNFα and IL-6 mRNA in the IRI livers was significantly attenuated by H2 S treatment, as was hepatic influx of Ly-6G positive granulocytes. Hepatic superoxide production after ischemia was attenuated by H2 S treatment. In hepatic ischemia/reperfusion injury, gaseous H2 S treatment is highly protective, substantially reducing necrosis, apoptosis and inflammation. Gaseous H2 S is therefore a very promising treatment for reducing IRI during hepatic transplantation.
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. e.m.bos@path.umcg.nl
Eelke M
EM
Bos
Pauline M
PM
Snijder
Henrike
H
Jekel
Michel
M
Weij
Jaklien C
JC
Leemans
Marcory C F
MC
van Dijk
Jan-Luuk
JL
Hillebrands
Ton
T
Lisman
Harry
H
van Goor
Henri G D
HG
Leuvenink
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D006862:Hydrogen Sulfide / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006862:Hydrogen Sulfide