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Transplantation:
doi: 10.1097/TP.0000000000000305
Basic and Experimental Research

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

Hatachi, Go1; Tsuchiya, Tomoshi1; Miyazaki, Takuro1; Matsumoto, Keitaro1; Yamasaki, Naoya1; Okita, Naoyuki2; Nanashima, Atsushi1; Higami, Yoshikazu2; Nagayasu, Takeshi1,3

Open Access
Supplemental Author Material
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Abstract

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.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.

Copyright © 2014 by Lippincott Williams & Wilkins

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