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.
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.
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.
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.