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01-07-2015 | Original Article

Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver

Authors: Shingo Shimada, Moto Fukai, Kenji Wakayama, Takahisa Ishikawa, Nozomi Kobayashi, Taichi Kimura, Kenichiro Yamashita, Toshiya Kamiyama, Tsuyoshi Shimamura, Akinobu Taketomi, Satoru Todo

Published in: Surgery Today | Issue 7/2015

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.

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.

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.

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.

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Title: Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver
Authors: Shingo Shimada
Moto Fukai
Kenji Wakayama
Takahisa Ishikawa
Nozomi Kobayashi
Taichi Kimura
Kenichiro Yamashita
Toshiya Kamiyama
Tsuyoshi Shimamura
Akinobu Taketomi
Satoru Todo
Publication date: 01-07-2015
Publisher: Springer Japan
Published in: Surgery Today / Issue 7/2015
Print ISSN: 0941-1291
Electronic ISSN: 1436-2813
DOI: https://doi.org/10.1007/s00595-014-1064-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Hydrogen sulfide augments survival signals in warm ischemia and reperfusion of the mouse liver

Abstract

Background and purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and purpose

Methods

Results

Conclusion

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