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Published on: November 27, 2016
Fatty Acid Binding Proteins for Improved Prediction and Monitoring of Radiation- induced Gastrointestinal Injury
Suchitra Sharma1, Aliza Rehan, Ajaswrata Dutta
1GI Radiobiology Research Laboratory, Radiomitigation Research Department, Institute of Nuclear Medicine and Allied Sciences (INMAS), Defence Research and Development Organization (DRDO), Brig. S.K Mazumdar Marg, Timarpur, Delhi 110054, INDIA.
Abstract:
Early detection and effective monitoring of gastrointestinal injury are needed for efficient medical management of the radiation-exposed victims. This study evaluated fatty acid-binding proteins (FABP1, FABP2, and FABP6) in combination to accurately predict and monitor radiation-induced gastrointestinal injury in C57Bl/6 mice. The response of FABPs was checked upon exposure to a range (2.5 Gy-20 Gy) of gamma radiation doses and their availability in serum from 2 h to 7 d. These alterations were correlated with structural changes in the intestine and the expression of genes encoding tight junction proteins, Zona occludens-1 and Occludin. Tissue-specific expression was also checked. FABP2 expression was found abundant and specific to the intestine, where it co-localized with FABP1 and FABP6. An increase in serum FABPs was noted in a dose- and time-specific manner, which correlated with radiation-mediated intestinal injury and downregulation of Zona occludens-1 and Occludin. FABP1, FABP2, and FABP6 were found to be upregulated at 9 Gy and above and were available in serum within 24 h of exposure. FABP1 and FABP2 were detected in serum between 24 h and 72 h, whereas FABP6 had a prolonged time window (24 h to 5 d). In serum, FABP1, FABP2, and FABP6 peaked at 24 h, 48 h and 72 h, respectively, suggesting that the three FABPs in combination can detect GI injury as early as 24 h. These proteins displayed reliable specificity based on ROC curve construction. Together, FABP1, FABP2, and FABP6 could detect and assess the progression of radiation-induced gastrointestinal injury rapidly, which may facilitate in managing exposed individuals following radiological emergencies.
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