Secretory Leukocyte Protease Inhibitor Decreases Renal Ischemia Reperfusion Injury

D. GUERRIERI, N. AMBROSI, H. ROMEO, F. CICORA, F. TONIOLO, P. CICORA, C. INCARDONA, E. CHULUYAN.

Poitiers

Congreso; The First International Meeting On Ischemia Reperfusion Injuries in Transplantation (IMIRT); 2012

Ischemia reperfusion injury (IRI) remains one of the major problems in solid organ transplantation. The aim of this study was to evaluate the effect of recombinant human secretory leukocyte protease inhibitor (SLPI) in a model of rat IRI. Materials and methods: bilateral ischemicprocedures were performed in male Sprague-Dawley ratsof 200-300 g. Renal artery and vein were clamped for 40 minutes. After 24 hours of reperfusion, the animals were sacrificed. There were four experimental groups: i) Sham (no IRI); ii) Control (IRI + control buffer); iii) SLPI (IRI+ SLPI); iv) dSLPI(IRI + SLPIwithout anti-serine protease activity). Animals were treated (250 m g / kg ip) with control buffer, SLPI or dSLPI,24 h pre-ischemia, during the ischemia and 6 hours post-ischemia. Results: Animals treated with SLPI or dSLPI showed lower levels of serum creatinine (control: 2.6 ± 1.0; SLPI: 1.2 ±0.8; dSLPI 0.45± 0.41 mg/dl, p <0.05 for SLPI anddSLPI) and blood urea nitrogen (control: 143 ± 9;SLPI: 63 ± 27; dSLPI: 46 ± 23 mg/dl, p <0.05 for SLPI anddSLPI) compared to control animals.Acute tubular necrosiswas less severe in animals treated withSLPI or dSLPI(Control: 63 ± 6;SLPI: 20 ± 3; dSLPI: 38 ± 7, p <0.01 for SLPI; p <0.05 for dSLPI). Furthermore, animals treated with SLPI or dSLPI showed lower levels of myeloperoxidase than control rats (Control: 370 ±34; SLPI: 230 ± 23; dSLPI: 260±22 EU/mg prot., p <0.001 for SLPI and dSLPI). Finally, qRT-PCR showed that the increased expression of genes for TNF-a, ED-1, MCP-1, CD86, CD14 and IL-10 produce by IRI was reduced by treatment with SLPI or dSLPI (p <0.05). Conclusion: overall this study demonstrates that treatment with SLPI or dSLPI reduces the IRI and improves the kidney function. Moreover, this effect is not dependent on the inhibitory serine protease activity of SLPI.