The Poly(Adenosine Diphosphate-Ribose) Polymerase Inhibitor PJ34 Reduces Pulmonary Ischemia-Reperfusion Injury in Rats

Background: Ischemia-reperfusion (I/R) injury after lung transplantation causes alveolar damage, lung edema, and acute rejection. Poly(adenosine diphosphate-ribose) polymerase (PARP) is a single-stranded DNA repair enzyme that induces apoptosis and necrosis after DNA damage caused by reactive oxygen species. We evaluated tissue protective effects of the PARP inhibitor (PARP-i) PJ34 against pulmonary I/R injury.Methods: Rats (total n=45) underwent a thoracotomy with left hilar isolation and saline administration (sham group) or thoracotomy with hilar clamping and saline administration (I/R group) or PJ34 administration (PARP-i group). Parameters were measured for 7 days after reperfusion.Results: Pathologic analysis revealed that reperfusion injury was drastically suppressed in the PARP-i group 2 days after reperfusion. Terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling–positive cells were significantly decreased in the PARP-i group compared to the I/R group (P<0.05). Accordingly, the wet-to-dry lung ratio in the I/R group was significantly higher compared with the PARP-i group (P=0.025). Four hours after reperfusion, serum tissue necrosis factor-α and interleukin-6 were significantly suppressed in the PARP-i group compared with the I/R group (P<0.05). Serum derivatives of reactive oxygen metabolites increased quickly and remained high in the I/R and PARP-i groups from 4 hr until 7 days after reperfusion. Interestingly, the serum biologic antioxidant potential in the PARP-i group was significantly higher than that in the I/R group from day 2 until day 7.Conclusion: The PARP-i decreased inflammation and tissue damage caused by pulmonary I/R injury. These beneficial effects of the PARP-i may be correlated with its antioxidative efficacy.;開始ページ : 618;終了ページ : 624;元資料の権利情報 : © 2014 Lippincott Williams & Wilkins.;元資料の権利情報 : This article is publised under the terms of the Creative Commons License Attribution-NonCommerical No Derivative 3.0 which allows readers to disseminate and reuse the article, as well as share and reuse the scientific material. It does not permit commercial exploitation or the creation of derivative works without specific permission. To view a copy of this license visit http://creativecommons.org/licenses/by-nc-nd/3.0.

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書名 The Poly(Adenosine Diphosphate-Ribose) Polymerase Inhibitor PJ34 Reduces Pulmonary Ischemia-Reperfusion Injury in Rats
著作者等 畑地 豪
書名別名 ポリADPリボースポリメレース阻害薬(PJ34)はラットにおける肺虚血再灌流障害を軽減する
出版元 Lippincott Williams & Wilkins
刊行年月 1963.1-
ISSN 00411337
NCID AA00868935
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言語 英語
出版国 アメリカ合衆国
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