Dataset Information

Superoxide mediates acute liver injury in irradiated mice lacking sirtuin 3.

ABSTRACT:

Aims

This study determined whether acute radiation-induced liver injury seen in Sirtuin3(-/-) mice after exposure to Cs-137 ?-rays was mediated by superoxide anion (O2(•-)).

Results

Male wild-type (WT) and SIRT3(-/-) mice were given 2×2?Gy whole-body radiation doses separated by 24?h and livers were harvested 20?h after the second dose. Ex vivo measurements in fresh frozen liver sections demonstrated 50% increases in dihydroethidium oxidation from SIRT3(-/-) animals, relative to WT animals, before irradiation, but this increase was not detected 20?h after radiation exposure. In addition, irradiated livers from SIRT3(-/-) animals showed significant hydropic degeneration, loss of MitoTracker Green FM staining, increased immunohistochemical staining for 3-nitrotyrosine, loss of Ki67 staining, and increased mitochondrial localization of p53. These parameters of radiation-induced injury were significantly attenuated by an intraperitoneal injection of 2?mg/kg of the highly specific superoxide dismutase mimic, GC4401, 30?min before each fraction.

Innovation

Sirtuin 3 (SIRT3) is believed to regulate mitochondrial oxidative metabolism and antioxidant defenses in response to acute radiation-induced liver injury. This work provides strong evidence for the causal role of O2(•-) in the liver injury process initiated by whole-body irradiation in SIRT3(-/-) mice.

Conclusion

These results support the hypothesis that O2(•-) mediates acute liver injury in SIRT3(-/-) animals exposed to whole-body ?-radiation and suggest that GC4401 could be used as a radio-protective compound in vivo.

SUBMITTER: Coleman MC

PROVIDER: S-EPMC3936509 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Publications

Superoxide mediates acute liver injury in irradiated mice lacking sirtuin 3.

Coleman Mitchell C MC Olivier Alicia K AK Jacobus James A JA Mapuskar Kranti A KA Mao Gaowei G Martin Sean M SM Riley Dennis P DP Gius David D Spitz Douglas R DR

Antioxidants & redox signaling 20130928 9

<h4>Aims</h4>This study determined whether acute radiation-induced liver injury seen in Sirtuin3(-/-) mice after exposure to Cs-137 γ-rays was mediated by superoxide anion (O2(•-)).<h4>Results</h4>Male wild-type (WT) and SIRT3(-/-) mice were given 2×2 Gy whole-body radiation doses separated by 24 h and livers were harvested 20 h after the second dose. Ex vivo measurements in fresh frozen liver sections demonstrated 50% increases in dihydroethidium oxidation from SIRT3(-/-) animals, relative to W ...[more]

PMID: 23919724

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Dataset Information

Superoxide mediates acute liver injury in irradiated mice lacking sirtuin 3.

Aims

Results

Innovation

Conclusion

Publications

Superoxide mediates acute liver injury in irradiated mice lacking sirtuin 3.

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