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Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver.
- Source :
-
Surgery today [Surg Today] 2015 Jul; Vol. 45 (7), pp. 892-903. Date of Electronic Publication: 2014 Nov 02. - Publication Year :
- 2015
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Abstract
- Background and Purpose: Hydrogen sulfide (H2S) ameliorates hepatic ischemia and reperfusion injury (IRI), but the precise mechanism remains elusive. We investigated whether sodium hydrogen sulfide (NaHS), a soluble derivative of H2S, would ameliorate hepatic IRI, and if so, via what mechanism.<br />Methods: Mice were subjected to partial warm ischemia for 75 min followed by reperfusion. Either NaHS or saline was administered intravenously 10 min before reperfusion. The liver and serum were collected 3, 6, and 24 h after reperfusion.<br />Results: In the NaHS(-) group, severe IRI was apparent by the ALT leakage, tissue injury score, apoptosis, lipid peroxidation, and inflammation (higher plasma TNF-α, IL-6, IL-1β, IFN-γ, IL-23, IL-17, and CD40L), whereas IRI was significantly ameliorated in the NaHS(+) group. These effects could be explained by the augmented nuclear translocation of Nrf2, and the resulting up-regulation of HO-1 and thioredoxin-1. Phosphorylation of the PDK-1/Akt/mTOR/p70S6k axis, which is known to mediate pro-survival and anti-apoptotic signals, was significantly augmented in the NaHS(+) group, with a higher rate of PCNA-positive cells thereafter.<br />Conclusion: NaHS ameliorated hepatic IRI by direct and indirect anti-oxidant activities by augmenting pro-survival, anti-apoptotic, and anti-inflammatory signals via mechanisms involving Nrf-2, and by accelerating hepatic regeneration via mechanisms involving Akt-p70S6k.
- Subjects :
- Animals
Apoptosis drug effects
Biomarkers metabolism
Blotting, Western
Immunohistochemistry
Liver drug effects
Liver metabolism
Male
Mice
Mice, Inbred C57BL
Oxidative Stress drug effects
Protective Agents pharmacology
Reperfusion Injury etiology
Reperfusion Injury metabolism
Sulfides pharmacology
Cytokines metabolism
Liver blood supply
Protective Agents therapeutic use
Reperfusion adverse effects
Reperfusion Injury prevention & control
Sulfides therapeutic use
Warm Ischemia adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1436-2813
- Volume :
- 45
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Surgery today
- Publication Type :
- Academic Journal
- Accession number :
- 25362520
- Full Text :
- https://doi.org/10.1007/s00595-014-1064-4