Background: Post-liver transplantation acute lung injury (ALI) severely affects patients' survival, whereas the mechanism is unclear and effective therapy is lacking. The authors postulated that reperfusion-induced increased oxidative stress plays a critical role in mediating post-liver transplantation ALI and that induction of heme oxgenase-1 (HO-1), an enzyme with anti-oxidative stress properties, can confer effective protection of lung against ALI.

Methods: Male Sprague-Dawley rats underwent autologous orthotopic liver transplantation (OALT) in the absence or presence of treatments with the selective HO-1 inducer (Hemin) or HO-1 inhibitor (ZnPP). Lung tissues were collected at 8 h after OALT, pathological scores and lung water content were evaluated; survival rate of rats was analyzed; protein expression of HO-1 was determined by western blotting, and nuclear translocation of Nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor(NF)-κB p65 were detected by Immunofluorescence staining. The inflammatory cytokines and oxidative indexes of lung tissue were determined.

Results: In lungs harvested at the early stage i.e. 8 h after OALT, Hemin treatment significantly increased superoxide dismutase activities, and reduced malondialdehyde, hydrogen peroxide, interleukin-6, myeloperoxidase, and tumor necrosis factor-α production,which were associated with increased HO-1 protein expression and lower pathological scores and increased survival rate of rats. The underline mechanisms might associate with activation of Nrf2 and inhibition of NF-κB p65 nuclear translocation. However, these changes were aggravated by ZnPP.

Conclusions: Hemin pretreatment, by enhancing HO-1 induction, increased lung antioxidant capacity and reduced inflammatory stress,protected the lung from OALT-induced ALI at early stage of reperfusion.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736160PMC
http://dx.doi.org/10.1186/s12967-016-0793-0DOI Listing

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