2001 Fiscal Year Final Research Report Summary
Interaction of nitric oxide and reactive oxygen on ADP-ribose-polymerase activation DNA damage
| Project/Area Number |
12671186
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | KINKI UNIVERSITY |
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Principal Investigator |
YONEKURA Takeo Kinki University School of Medicine, Assistant Professor, 医学部附属病院, 助教授 (00258021)
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| Co-Investigator(Kenkyū-buntansha) |
KOSUMI Takuya Kinki University School of Medicine, Lecturer, 医学部附属病院, 講師 (90340827)
YAGI Makoto Kinki University School of Medicine, Lecturer, 医学部, 講師 (20191091)
OOYANAGI Harumasa Kinki University School of Medicine, Chief Professor, 医学部, 教授 (00030958)
HIGASHINO Hideaki Kinki University School of Medicine, Chief Professor, 医学部, 教授 (40122098)
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| Project Period (FY) |
2000 – 2001
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| Keywords | nitric oxide / oxidant stress / ischemia reperfusion injury / poly(ADP-ribose)polymerase / 3-aminobenzamide / ATP / DNA damage / apoptosis |
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| Research Abstract |
Purpose : To reveal the mechanism of ischemia reperfusion injury, we evaluate intracellular ATP levels and DNA damage and organ damage in ischemia reperfusion with inhibition of poly(ADP-ribose) polymerase activation and NO production. Methods : 60 min. ischemia and 180 min. reperfusion in the 70% liver of the male Wister rats were performed. The 3AB group rats received PARS inhibitor, 3-aminobenzamide, and the L-NAME group rats received NO inhibitor, L-NAME, before ischemia. The control group rats were infused saline. The sham group rats were treated only dissection of portal area without ischemia reperfusion. Tissue damage and DNA damage was evaluated both in the ischemia reperfused liver (IR-liver) and the non-ischemia reperfused liver (NIR-liver). Nitrotyrosine stain was performed for evaluating tissue damage by ONOO-. Serum ALP levels, intrahepatic ATP levels and Nitrotyrosine levels were also evaluated in each group. Results : The L-NAME group had highest serum ALT levels compare
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d with the control and the 3AB groups. The control and the L- NAME groups had severe tissue and DNA damages in the IR-liver, while the 3AB group had mild tissue and DNA damages in the IR-liver. There were not differences in the NIR-liver among 4 groups. The IR-love in the control and the 3AB groups had high nitrotyrosine staining. They also had high tissue concentrations of nitrotyrosine. The L-NAME group did not have any nitrotyrosine staining or production. In the IR-liver, the 3AB group had higher intrahepatic ATP levels than the control and the L-NAME groups. In the NIR-liver, although the control and the L-NAME groups had lower levels of intrahepatic ATP levels compared with the sham group, the 3AB group had same intrahepatic ATP levels as the sham group. Conclusion : We concluded that multiple organ failure developed in the ischemia reperfusion injury would be due to consumption of intracellular ATP with activation of PARS to repair DNA damage caused by free radicals in ischemia reperfusion. Less
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