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 ( LCN 2) 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 LCN 2 increase after single dose liver irradiation along with hepatic LCN 2 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 K upffer cells were isolated from the liver of healthy rats and irradiated ex‐vivo . Results After liver irradiation, LCN 2 serum levels increased significantly up to 2.7 μg/ml within 6 h and stayed elevated over 24 h. LCN 2 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 LCN 2. LCN 2+ 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 LCN 2 gene expression as compared to myofibroblasts and K upffer cells . IL ‐1β treatment further increased LCN 2 gene expression in cultured hepatocytes . Conclusions Single dose liver irradiation induces a significant increase in LCN 2 serum levels, comparable to the induction of acute phase proteins. We suggest LCN 2 as marker for the early phase of radiation‐induced tissue damage.