An exogenous hydrogen sulphide donor, NaHS, inhibits the nuclear factor κB inhibitor kinase/nuclear factor κb inhibitor/nuclear factor-κB signaling pathway and exerts cardioprotective effects in a rat hemorrhagic shock model.
Hemorrhagic shock (HS) is a common condition and leading cause of death in trauma patients universally. Severe inflammatory responses during HS finally lead to multiple-organ failure. Hydrogen sulphide (H₂S) is increasingly recognized as an important signaling molecule with various protective effects. In the present study, we investigated the antiinflammatory and cardioprotective effects of an exogenous H₂S donor, sodium hydrosulfide (NaHS), in an HS rat model. Male Sprague-Dawley rats were randomly divided into the sham-operated, sham-operated treated with NaHS (28 µmol/kg, intraperitoneally (i.p.)), HS, and HS treated with NaHS (28 µmol/kg, i.p.) groups. The HS groups were subjected to mimicked HS for 1 h and then treated with NaHS or left untreated. The rats were then resuscitated with Ringer lactate solution for 1 h. Myocardial enzymes and inflammatory cytokines were evaluated. Morphologic changes in cardiac tissue and ultrastructural injury were also analyzed. HS resulted in significant hemodynamic deterioration and increased myocardial enzyme and inflammatory cytokine levels. Intraperitoneal administration of NaHS significantly prevented hemodynamic deterioration and decreased the elevation of myocardial enzymes. NaHS also inhibited the nuclear factor κB inhibitor kinase (IKK)/nuclear factor κB inhibitor (IκB)/nuclear factor κB (NF-κB) signaling pathway. The results suggest that NaHS exerts cardioprotective effects against HS. The protective effects of NaHS may occur via down-regulation of the IKK/IκB/NF-κB signaling pathway.
Department of Anesthesiology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710032, P. R. China.
Cao
C
Gao
Dun-Quan
DQ
Xu
Chang-Jun
CJ
Gao
Qian
Q
Ding
Li-Nong
LN
Yao
Zhi-Chao
ZC
Li
Wei
W
Chai
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013440:Sulfides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D002316:Cardiotonic Agents; D020672:I-kappa B Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D013440:Sulfides; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D051550:I-kappa B Kinase; D003402:Creatine Kinase; C025451:sodium bisulfide; D006862:Hydrogen Sulfide