Abstract

e13039 Background: Lipocalin-2 is a pleiotropic protein synthesized under acute phase conditions. The source of increased serum levels and the major organ responsible for its production are still unknown. The aim of our study was to prospectively evaluate the Lipocalin-2 (LCN-2) expression in rat liver exposed to single dose x-irradiation. Methods: A single dose of 25 Gy 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 hours after irradiation along with sham irradiated control. Blood was taken for ELISA of LCN-2, and organs were removed and deep-frozen for RT-PCR and Western Blot or prepared for immunostaining. Furthermore, hepatocytes, myofibroblasts and Kupffer cells were isolated from the liver of healthy rats and irradiated with 2 Gy ex-vivo. Results: LCN-2 serum levels increased significantly (2.5 mg/ml) within 24 hours after direct liver irradiation. In the liver, LCN-2 specific transcripts increased significantly up to 552 ±109-fold at 24 hours which was further confirmed by Western blot analysis. Immunohistology of liver sections detected positivity in recruited granulocytes within 1 hour after irradiation around the central and portal areas. Ex-vivo irradiated hepatocytes showed a significantly higher LCN-2 expression as compared to myofibroblasts and Kupffer cells. Treatment of isolated, irradiated hepatocytes with acute phase cytokines (IL-6, IL-1b, TNFa, IL-6+TNFa) showed that the main inducer of LCN-2 was IL-1β. Conclusions: Single dose liver irradiation, induces a fast and significant increase of LCN-2 serum level. Hepatocytes are the major producers of LCN-2 in oxidative stress conditions. LCN-2 may represent a new serum-biomarker when the liver is hit by irradiation.

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