Serum Lipocalin2 is a potential biomarker of liver irradiation damage.

Background/Aim IL-6 - IL-1- lipocalin2 (LCN2) - liver irradiation - oxidative stress - TNF-a Lipocalin2 ( LCN2) is an acute phase protein. The source of its increased serum level in oxidative stress conditions ( ROS) remains still unknown. We prospectively evaluate the serum LCN2 increase after single dose liver irradiation along with hepatic LCN2 gene and protein expression. Methods A single dose of 25 Gray was administered percutaneously to the liver of randomly paired rats after a planning CT scan. Male Wistar rats were sacrificed 1, 3, 6, 12, 24 and 48 h after irradiation along with sham-irradiated controls. ELISA, RT- PCR, Western blot and immunofluorescence staining was performed. Furthermore, hepatocytes, myofibroblasts and Kupffer cells were isolated from the liver of healthy rats and irradiated ex-vivo. Results After liver irradiation, LCN2 serum levels increased significantly up to 2.7 μg/ml within 6 h and stayed elevated over 24 h. LCN2 specific transcripts increased significantly up to 552 ± 109-fold at 24 h after liver irradiation, which was further confirmed at protein level. α2-macroglobulin and hemoxygenase-1 also showed an increase, but the magnitude was less as compared to LCN2. LCN2+ granulocytes were detected within 1 h after irradiation around central and portal fields and remained high during the course of study. Ex-vivo irradiated hepatocytes (2.4 ± 0.6-fold) showed a higher LCN2 gene expression as compared to myofibroblasts and Kupffer cells. IL-1β treatment further increased LCN2 gene expression in cultured hepatocytes. Conclusions Single dose liver irradiation induces a significant increase in LCN2 serum levels, comparable to the induction of acute phase proteins. We suggest LCN2 as marker for the early phase of radiation-induced tissue damage. [ABSTRACT FROM AUTHOR]