Ischemia Reperfusion Injury (IRI) causes Local Release of Free Heme which Aggravates Inflammation and Contributes to Delayed Graft Function

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Abstract

Methods

Renal IRI was induced by 15, 35 and 45 min unilateral renal pedicle clamping in mice. Sham surgery served as control. Mice were sacrificed at 2 and 4 and 24 hours after IRI. Free heme was measured in the kidney and systemic complement activation was measured in blood samples. qPCR for pro-inflammatory cytokine expression, histology and immunohistochemistry for acute kidney injury were done.

Results

In correlation with increased duration of ischemia time the free heme generation in the tissue increased and enhanced local pro-inflammatory cytokine release (TNF-alpha, MCP-1, IL-6) was measured. AKI score and inflammatory cell infiltration into the tissue increased as well. Complement activation was higher in correlation with longer ischemia time

Conclusion

Free heme release in ischemic organs aggravates local inflammation. Strategies to reduce free heme production prior to solid organ transplantation would be promising therapeutic approaches to reduce the risk of DGF.

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